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Sample records for alcohol-related neurodevelopmental disorder

  1. Cortical morphology in children with alcohol-related neurodevelopmental disorder

    PubMed Central

    Rajaprakash, Meghna; Chakravarty, M Mallar; Lerch, Jason P; Rovet, Joanne

    2014-01-01

    Introduction It is well established that individuals exposed to alcohol in utero have reduced cortical grey matter volumes. However, the candidate determinants of these reductions, cortical thickness (CT) and surface area (SA), have not been investigated exclusively in alcohol-related neurodevelopmental disorder (ARND), the most prevalent fetal alcohol spectrum disorder subgroup that lacks the characteristic facial dysmorphology. Methods T1-weighted magnetic resonance imaging scans were obtained from 88 participants (8–16 years), 36 diagnosed with ARND and 52 typically developing controls. Scans were submitted to the CIVET pipeline (version 1.1.10). Deformable models were used to construct the inner white matter surfaces and pial surfaces from which CT and SA measures were derived. Group differences in cortical volume, CT, and SA were computed using a general linear model covaried for age, sex, and handedness. Results Global cortical volume reductions in ARND did not reflect CT, which did not differ between groups. Instead, volume decreases were consistent with global SA reductions in bilateral frontal and temporal as well as right occipital regions. Local reductions in SA were observed in the right superior temporal gyrus and the right occipital-temporal region. Conclusion Results suggest that in ARND, prenatal alcohol exposure perturbs global SA to a greater degree than CT, particularly in the right temporal lobe. PMID:24653953

  2. Reversing Neurodevelopmental Disorders in Adults

    PubMed Central

    Ehninger, Dan; Li, Weidong; Fox, Kevin; Stryker, Michael P.; Silva, Alcino J.

    2009-01-01

    Abnormalities in brain development, thought to be irreversible in adults, have long been assumed to underlie the neurological and psychiatric symptoms associated with neurodevelopmental disorders. Surprisingly, a number of recent animal model studies of neurodevelopmental disorders demonstrate that reversing the underlying molecular deficits can result in substantial improvements in function even if treatments are started in adulthood. These findings mark a paradigmatic change in the way we understand and envision treating neurodevelopmental disorders. PMID:19109903

  3. Sleep Disturbances in Neurodevelopmental Disorders.

    PubMed

    Robinson-Shelton, Althea; Malow, Beth A

    2016-01-01

    Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia. PMID:26719309

  4. Emerging Pharmacotherapies for Neurodevelopmental Disorders

    PubMed Central

    Wetmore, Daniel Z.; Garner, Craig C.

    2010-01-01

    A growing and interdisciplinary translational neuroscience research effort for neurodevelopmental disorders (NDDs) is investigating the mechanisms of dysfunction and testing effective treatment strategies in animal models and, when possible, in the clinic. NDDs with a genetic basis have received particular attention. Transgenic animals that mimic genetic insults responsible for disease in man have provided insight about mechanisms of dysfunction, and, surprisingly, have shown that cognitive deficits can be addressed in adult animals. This review will present recent translational research based on animal models of genetic NDDs, as well as pharmacotherapeutic strategies under development to address deficits of brain function for Down syndrome, fragile X syndrome, Rett syndrome, neurofibromatosis-1, tuberous sclerosis, and autism. Although these disorders vary in underlying causes and clinical presentation, common pathways and mechanisms for dysfunction have been observed. These include abnormal gene dosage, imbalance among neurotransmitter systems, and deficits in the development, maintenance and plasticity of neuronal circuits. NDDs affect multiple brain systems and behaviors that may be amenable to drug therapies that target distinct deficits. A primary goal of translational research is to replace symptomatic and supportive drug therapies with pharmacotherapies based on a principled understanding of the causes of dysfunction. Based on this principle, several recently developed therapeutic strategies offer clear promise for clinical development in man. PMID:20814256

  5. Treatment of neurodevelopmental disorders in adulthood

    PubMed Central

    Castrén, Eero; Elgersma, Ype; Maffei, Lamberto; Hagerman, Randi

    2012-01-01

    Brain development in neurodevelopmental disorders has been considered to comprise a sequence of critical periods and abnormalities occurring during early development have been considered irreversible in adulthood. However, findings in mouse models of neurodevelopmental disorders, including Fragile X, Rett and Down Syndromes and Neurofibromatosis type I suggest that it is possible to reverse certain molecular, electrophysiological and behavioral deficits associated with these disorders in adults by genetic or pharmacological manipulations. Furthermore, recent studies have suggested that critical period-like plasticity can be reactivated in the adult brain by environmental manipulations or by pharmacotherapy. These studies open up a tantalizing possibility that targeted pharmacological treatments in combination with regimes of training or rehabilitation might alleviate or reverse the symptoms of neurodevelopmental disorders even after the end of critical developmental periods. Even though translation from animal experimentation to clinical practice is challenging, these results suggest a rational basis for treatment of neurodevelopmental disorders in adulthood. PMID:23055475

  6. Journal of Neurodevelopmental Disorders reviewer acknowledgement 2012

    PubMed Central

    2013-01-01

    Contributing reviewers The editors of Journal of Neurodevelopmental Disorders would like to thank all of our reviewers who have contributed to the journal in volume 4 (2012). High quality and timely reviews are critical to the overall quality of the journal. We are committed to providing a unique and important outlet for scholarship regarding neurodevelopmental disorders and are indebted to the outstanding reviewers who have contributed their time over the last year in helping us to reach this goal. PMID:23517765

  7. School Neuropsychology Consultation in Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Decker, Scott L.

    2008-01-01

    The role of school psychologists with training in neuropsychology is examined within the context of multitiered models of service delivery and educational reform policies. An expanded role is suggested that builds on expertise in the assessment of neurodevelopmental disorders and extends to broader tiers through consultation practice. Changes in…

  8. Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders.

    PubMed

    Verkhratsky, Alexei; Parpura, Vladimir

    2016-01-01

    Astroglial cells represent a main element in the maintenance of homeostasis and providing defense to the brain. Consequently, their dysfunction underlies many, if not all, neurological, neurodevelopmental and neuropsychiatric disorders. General astrogliopathy is evident in diametrically opposing morpho-functional changes in astrocytes, i.e. their hypertrophy along with reactivity or atrophy with asthenia. Neurological disorders with astroglial participation can be genetic, of which Alexander disease is a primary sporadic astrogliopathy, environmentally caused, such as heavy metal encephalopathies, or neurodevelopmental in origin. Astroglia contribute to neurodegenerative processes seen in amyotrophic lateral sclerosis, Alzheimer's and Huntington's diseases. Furthermore, astroglia also play a role in major neuropsychiatric disorders, ranging from schizophrenia to depression, as well as in addictive disorders. PMID:25843667

  9. The Cerebellum and Neurodevelopmental Disorders.

    PubMed

    Stoodley, Catherine J

    2016-02-01

    Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior. PMID:26298473

  10. Drosophila Modeling of Heritable Neurodevelopmental Disorders

    PubMed Central

    Gatto, Cheryl L.; Broadie, Kendal

    2011-01-01

    Heritable neurodevelopmental disorders are multifaceted disease conditions encompassing a wide range of symptoms including intellectual disability, cognitive dysfunction, autism and myriad other behavioral impairments. In cases where single, causative genetic defects have been identified, such as Angelman syndrome, Rett syndrome, Neurofibromatosis Type 1 and Fragile X syndrome, the classical Drosophila genetic system has provided fruitful disease models. Recent Drosophila studies have advanced our understanding of UBE3A, MECP2, NF1 and FMR1 function, respectively, in genetic, biochemical, anatomical, physiological and behavioral contexts. Investigations in Drosophila continue to provide the essential mechanistic understanding required to facilitate the conception of rational therapeutic treatments. PMID:21596554

  11. Correlates of Early Assessment of Neurodevelopmental Disorders in Lebanon

    ERIC Educational Resources Information Center

    Dirani, Leyla Akoury; Salamoun, Mariana

    2014-01-01

    Children with neurodevelopmental disorders who receive early therapeutic interventions present a better developmental pathway than children who do not. Early assessment of neurodevelopmental disorders is the first step in this process. This study aims at describing the variables that are in play in the first assessment of children with autism…

  12. Organ Transplantation for Individuals with Neurodevelopmental Disorders.

    PubMed

    Overby, Kim J; Fins, Joseph J

    2016-04-01

    In 1996, Sandra Jensen became the first person with Down syndrome to receive a heart-lung transplant. Although it took place almost 20 years ago, her experience continues to shed light on contemporary challenges that individuals with neurodevelopmental disorders face in securing access to transplantation. While overt discrimination has decreased, barriers persist in physician referrals, center-specific decisionmaking regarding wait-listing, and the provision of accommodations for optimizing the assessment and medical management of these individuals. These issues arise from the persistent biases and assumptions of individuals as well as those of a healthcare system that is inadequately positioned to optimally serve the medical needs of the growing number of individuals with functional impairments. More data and greater transparency are needed to understand the nature and extent of ongoing access problems; however, long-term solutions will require changes at the healthcare professional, regional transplant center, and national levels. PMID:26957452

  13. Genetic and Environmental Factors in Complex Neurodevelopmental Disorders

    PubMed Central

    van Loo, K.M.J; Martens, G.J.M

    2007-01-01

    Complex neurodevelopmental disorders, such as schizophrenia, autism, attention deficit (hyperactivity) disorder, (manic) depressive illness and addiction, are thought to result from an interaction between genetic and environmental factors. Association studies on candidate genes and genome-wide linkage analyses have identified many susceptibility chromosomal regions and genes, but considerable efforts to replicate association have been surprisingly often disappointing. Here, we summarize the current knowledge of the genetic contribution to complex neurodevelopmental disorders, focusing on the findings from association and linkage studies. Furthermore, the contribution of the interaction of the genetic with environmental and epigenetic factors to the aetiology of complex neurodevelopmental disorders as well as suggestions for future research are discussed. PMID:19412416

  14. The GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders.

    PubMed

    Braat, Sien; Kooy, R Frank

    2015-06-01

    Intellectual disability, autism spectrum disorder, and epilepsy are prime examples of neurodevelopmental disorders that collectively affect a significant percentage of the world population. Recent technological breakthroughs allowed the elucidation of the genetic causes of many of these disorders. As neurodevelopmental disorders are genetically heterogeneous, the development of rational therapy is extremely challenging. Fortunately, many causative genes are interconnected and cluster in specific cellular pathways. Targeting a common node in such a network would allow us to interfere with a series of related neurodevelopmental disorders at once. Here, we argue that the GABAergic system is disturbed in many neurodevelopmental disorders, including fragile X syndrome, Rett syndrome, and Dravet syndrome, and is a key candidate target for therapeutic intervention. Many drugs that modulate the GABAergic system have already been tested in animal models with encouraging outcomes and are readily available for clinical trials. PMID:26050032

  15. [Guideline-oriented treatment of alcohol-related disorders].

    PubMed

    Mann, K; Hoch, E; Batra, A; Bonnet, U; Günthner, A; Reymann, G; Soyka, M; Wodarz, N; Schäfer, M

    2016-01-01

    Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15% of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved.This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30-40% could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year. PMID:26670021

  16. Early intervention in neurodevelopmental disorders: underlying neural mechanisms.

    PubMed

    Cioni, Giovanni; Inguaggiato, Emanuela; Sgandurra, Giuseppina

    2016-03-01

    Neurodevelopmental disorders affect motor, cognitive, language, learning, and behavioural development with lifelong consequences. Early identification of infants at risk for neurodevelopmental disorders is a major prerequisite for intervention programmes. This ensures that interventions which aim to positively modify the natural history of these disorders can start in the first weeks or months of life. As indicated by recent scientific evidence, gene abnormalities or congenital brain lesions are not the sole determinants for the neurodevelopmental outcome of affected infants. In fact, environment and experience may modify brain development and improve the outcome in infants at risk for neurodevelopmental disorders. In this review, we analyse the complexity and sensitivity of the brain to environmental stimuli, highlighting clinical effects of early intervention, mainly reported so far in preterm infants, and summarizing the effects of enriched environment on human and animal models. Finally, we discuss some new approaches to early intervention, based on recent neurophysiological theories and new breakthroughs in biotechnologies for diagnosis and rehabilitation. PMID:27027609

  17. GABAergic dysfunction in pediatric neuro-developmental disorders

    PubMed Central

    Smith-Hicks, Constance L.

    2013-01-01

    The GABAergic system is central to the development and functional maturation of the nervous system. Emerging evidence support the role of GABAergic dysfunction in neuro-developmental disorders. This review presents the molecules and mechanisms that underlie GABA system dysfunction in several neuro-developmental disorders presenting in childhood. The impact on synaptic plasticity, neuronal circuit function and behavior, followed by targeted treatment strategies are discussed. PMID:24391546

  18. A molecular model for neurodevelopmental disorders

    PubMed Central

    Gigek, C O; Chen, E S; Ota, V K; Maussion, G; Peng, H; Vaillancourt, K; Diallo, A B; Lopez, J P; Crapper, L; Vasuta, C; Chen, G G; Ernst, C

    2015-01-01

    Genes implicated in neurodevelopmental disorders (NDDs) important in cognition and behavior may have convergent function and several cellular pathways have been implicated, including protein translational control, chromatin modification, and synapse assembly and maintenance. Here, we test the convergent effects of methyl-CpG binding domain 5 (MBD5) and special AT-rich binding protein 2 (SATB2) reduced dosage in human neural stem cells (NSCs), two genes implicated in 2q23.1 and 2q33.1 deletion syndromes, respectively, to develop a generalized model for NDDs. We used short hairpin RNA stably incorporated into healthy neural stem cells to supress MBD5 and SATB2 expression, and massively parallel RNA sequencing, DNA methylation sequencing and microRNA arrays to test the hypothesis that a primary etiology of NDDs is the disruption of the balance of NSC proliferation and differentiation. We show that reduced dosage of either gene leads to significant overlap of gene-expression patterns, microRNA patterns and DNA methylation states with control NSCs in a differentiating state, suggesting that a unifying feature of 2q23.1 and 2q33.1 deletion syndrome may be a lack of regulation between proliferation and differentiation in NSCs, as we observed previously for TCF4 and EHMT1 suppression following a similar experimental paradigm. We propose a model of NDDs whereby the balance of NSC proliferation and differentiation is affected, but where the molecules that drive this effect are largely specific to disease-causing genetic variation. NDDs are diverse, complex and unique, but the optimal balance of factors that determine when and where neural stem cells differentiate may be a major feature underlying the diverse phenotypic spectrum of NDDs. PMID:25966365

  19. Genes and sex hormones interaction in neurodevelopmental disorders.

    PubMed

    Romano, Emilia; Cosentino, Livia; Laviola, Giovanni; De Filippis, Bianca

    2016-08-01

    The prevalence, age of onset and symptomatology of many neurodevelopmental disorders strongly differ between genders. This review examines sex biases in human neurodevelopmental disorders and in validated animal models. A focus is made on disorders of well-established genetic origin, such as Rett syndrome, CDKL5-associated disorders, Fragile X and Down syndrome. Autism is also addressed, given its paradigmatic role as a sex-biased neurodevelopmental disorder. Reviewed literature confirms that a complex interaction between genetic factors and sex hormones may underlie the differential susceptibility of genders and may impact the severity of symptoms in most of the analyzed neurodevelopmental disorders. Even though further studies addressing the advantages and disadvantages conferred by biological sex in this class of disorders are needed to disentangle the underlying mechanisms, present findings suggest that modulation of sex steroid-related pathways may represent an innovative approach for these diseases. Much effort is now expected to unravel the potential therapeutic efficacy of drugs targeting sex hormones-related signaling pathways in neurodevelopmental disorders of well-established genetic origin. PMID:26952805

  20. [Motor disorders in neurodevelopmental disorders. Tics and stereotypies].

    PubMed

    Eirís-Puñal, Jesús

    2014-02-24

    Tics are repetitive, sharp, rapid, non-rhythmic movements or utterances that are the result of sudden, abrupt and involuntary muscular contractions. Stereotypies are repetitive, apparently impulsive, rhythmic, purposeless movements that follow an individual repertoire that is specific to each individual and that occur under a variable time pattern, which may be either transient or persistent. Both are included in the Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5), among the neurodevelopmental disorders, and together with coordination development disorder go to make up the group of motor disorders. For tics, the categories of 'Tourette's disorder', 'chronic motor or vocal tic disorder' and 'unspecified tic disorder' have been maintained, whereas the category 'transient tics' has disappeared and 'provisional tic disorder' and 'other specified tic disorders' have been incorporated. Within stereotypic movement disorder, the DSM-5 replaces 'non-functional' by 'apparently purposeless'; the thresholds of the need for medical care are withdrawn and replaced with the manual's standard involvement criterion; mental retardation is no longer mentioned and emphasis is placed on the severity of the stereotypic movement; and a criterion concerning the onset of symptoms and specifiers of the existence or not of self-injurious behaviours have been added, together with the association with genetic or general medical diseases or extrinsic factors. Moreover, a categorisation depending on severity has also been included. PMID:25252672

  1. Melatonin for sleep problems in children with neurodevelopmental disorders.

    PubMed

    2015-10-01

    Children with neurodevelopmental disorders are at risk of sleep problems, typically difficulty getting to sleep, sleep/wake rhythm disturbances and reduced duration of sleep (insomnia). This may be associated with abnormally timed or inadequate secretion of melatonin, a naturally-occurring hormone involved in coordinating the body's sleep-wake cycle. Previously, we reviewed the use of a melatonin product licensed for primary insomnia in adults aged over 55 years. Here we review off-label and unlicensed use of melatonin in children with attention-deficit hyperactivity disorder (ADHD) or autism spectrum disorder or related neurodevelopmental disorders. PMID:26471270

  2. School performance and alcohol-related disorders in early adulthood: a Swedish national cohort study

    PubMed Central

    Gauffin, Karl; Vinnerljung, Bo; Hjern, Anders

    2015-01-01

    Background Alcohol misuse is an important global health determinant and a major contributor to health inequalities. We aimed to investigate the association between school performance and alcohol-related disorders in early adulthood in a longitudinal register-based national cohort study. Methods We followed a register-based national cohort of Swedish citizens born 1973–1984 (N = 948 440) from compulsory school graduation at age 15–16 to 2009. We divided the population into five groups: high school marks (> mean + 1 SD); high average (between mean and mean + 1 SD); low average (between mean and mean − 1 SD); low (< mean – 1SD); and missing. Cox proportional hazard models were used to investigate the relation between school marks at time of graduation and hospital care for alcohol-related disorders in early adulthood. Results There was a steep gradient in the risk of alcohol-related disorders related to school performance. In comparison with peers in the top category of school marks, students with low marks had adjusted hazard ratios of 8.02 [95% confidence interval (CI) 7.20 to 8.91], low average 3.02 (2.72 to 3.35) and high average 1.55 (1.39 to 1.73). The risk associated with low school marks was stronger in the male population and in the group from high socioeconomic background. Conclusions The study demonstrated a strong graded relation between low school performance and alcohol-related disorders in young adulthood. School performance should be taken into account when developing prevention programmes/policies targeting alcohol misuse among teenagers and young adults, especially if the aim is to reach high-risk groups. PMID:25797580

  3. Brain Imaging in Children with Neurodevelopmental Disorders.

    ERIC Educational Resources Information Center

    Mantovani, John F.

    1994-01-01

    This article reviews neuroimaging techniques such as cranial ultrasound, computed tomography scanning, and magnetic resonance imaging. Their roles in the care of children with neurodevelopmental disabilities include identification of high-risk infants, establishment of the diagnosis and prognosis in affected children, and enhancement of discussion…

  4. Gastrointestinal Disorders in Children with Neurodevelopmental Disabilities

    ERIC Educational Resources Information Center

    Sullivan, Peter B.

    2008-01-01

    Children with neurodevelopmental disabilities such as cerebral palsy (CP), spina bifida, or inborn errors of metabolism frequently have associated gastrointestinal problems. These include oral motor dysfunction leading to feeding difficulties, risk of aspiration, prolonged feeding times, and malnutrition with its attendant physical compromise.…

  5. Adaptive Profiles in Autism and Other Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar

    2015-01-01

    We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale…

  6. A compensatory role for declarative memory in neurodevelopmental disorders.

    PubMed

    Ullman, Michael T; Pullman, Mariel Y

    2015-04-01

    Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

  7. Affective instability, family history of mood disorders, and neurodevelopmental disturbance.

    PubMed

    Berenbaum, Howard; Bredemeier, Keith; Boden, M Tyler; Thompson, Renee J; Milanak, Melissa

    2011-07-01

    The association between affective instability and both family history of mood disorders and signs of neurodevelopmental disturbance was examined in a sample of 303 adults. Affective instability was measured using the borderline personality disorder "affective instability due to a marked reactivity of mood" diagnostic criterion as assessed dimensionally using the Personality Disorder Interview--IV. Participants were interviewed concerning family history of mood disorders, with family history coded using the Family History Research Diagnostic Criteria. Minor physical anomalies, inconsistent hand use, and dermatoglyphic asymmetries were used to index neurodevelopmental disturbance. Affective instability was associated with elevated rates of family history of mood disorders, particularly among individuals who exhibited inconsistent hand use and greater minor physical anomalies. These associations could not be accounted for by shared variance with age, gender, negative affect, or personal history of mood disorders. PMID:22448768

  8. A compensatory role for declarative memory in neurodevelopmental disorders

    PubMed Central

    Ullman, Michael T.; Pullman, Mariel Y.

    2015-01-01

    Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

  9. Recurring alcohol-related care between 1998 and 2007 among people treated for an alcohol-related disorder in 1997: A register study in Stockholm County

    PubMed Central

    2011-01-01

    Background Inpatient care for alcohol intoxication is increasing in Sweden, especially among young women. Since it is well known that alcohol disorder is a chronic relapsing illness, this study examines the extent to which people return for more care. Method All inpatients with alcohol-related diagnoses in Stockholm County during 1997 were followed prospectively to 2007 through registers. The proportion reappearing for the same diagnosis, other alcohol-related inpatient, or outpatient care each year after baseline, as well as the number of years the inpatients reappeared were calculated (n = 2735). Three diagnoses were examined separately; alcohol dependence, harmful use of alcohol, and alcohol intoxication. Results Three out of five inpatients with an alcohol diagnoses reappeared for more alcohol-related inpatient care during the following decade. The proportion returning was largest the year after baseline and then decreased curvilinearly over time. The inclusion of outpatient care increased proportions, but did not change patterns. Of those with an alcohol dependence diagnosis at baseline 42 percent returned for more alcohol-related inpatient care the first, 28 percent the fifth, and 25 percent the tenth year. Corresponding proportions for harmful use and intoxication were smaller. One in five among those with an alcohol dependence returned for more than five of the ten years. Ordered logistic regressions confirmed that besides diagnosis, age and gender were independently related to the number of years returning to care. Conclusions While middle-aged males with alcohol dependence were in a revolving door, young female inpatients with intoxication diagnosis returned to a comparably lower degree. PMID:21771291

  10. ER Stress-induced Aberrant Neuronal Maturation and Neurodevelopmental Disorders.

    PubMed

    Kawada, Koichi; Iekumo, Takaaki; Kaneko, Masayuki; Nomura, Yasuyuki; Okuma, Yasunobu

    2016-01-01

    Neurodevelopmental disorders, which include autism spectrum disorder, are congenital impairments in the growth and development of the central nervous system. They are mainly accentuated during infancy and childhood. Autism spectrum disorder may be caused by environmental factors, genomic imprinting of chromosome 15q11-q13 regions, and gene defects such as those in genes encoding neurexin and neuroligin, which are involved in synaptogenesis and synaptic signaling. However, regardless of the many reports on neurodevelopmental disorders, the pathogenic mechanism and treatment of neurodevelopmental disorders remain unclear. Conversely, it has been reported that endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases. ER stress is increased by environmental factors such as alcohol consumption and smoking. Here we show the recent results on ER stress-induced neurodevelopmental disorders. ER stress led to a decrease in the mRNA levels of the proneural factors Hes1/5 and Pax6, which maintain an undifferentiated state of the neural cells. This stress also led to a decrease in nestin expression and an increase in beta-III tubulin expression. In addition, dendrite length was shortened by ER stress in microtubule-associated protein-2 (MAP-2) positive cells. However, the ubiquitin ligase HRD1 expression was increased by ER stress. By suppressing HRD1 expression, the ER stress-induced decrease in nestin and MAP-2 expression and increase in beta-III tubulin returned to control levels. Therefore, we suggest that ER stress induces abnormalities in neuronal differentiation and maturation via HRD1 expression. These results suggest that targeting ER stress may facilitate quicker approaches toward the prevention and treatment of neurodevelopmental disorders. PMID:27252060

  11. Treatments for Neurodevelopmental Disorders: Evidence, Advocacy, and the Internet

    ERIC Educational Resources Information Center

    Di Pietro, Nina C.; Whiteley, Louise; Mizgalewicz, Ania; Illes, Judy

    2013-01-01

    The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly-trafficked advocacy websites for autism, cerebral…

  12. Reducing neurodevelopmental disorders and disability through research and interventions.

    PubMed

    Boivin, Michael J; Kakooza, Angelina M; Warf, Benjamin C; Davidson, Leslie L; Grigorenko, Elena L

    2015-11-19

    We define neurodevelopment as the dynamic inter-relationship between genetic, brain, cognitive, emotional and behavioural processes across the developmental lifespan. Significant and persistent disruption to this dynamic process through environmental and genetic risk can lead to neurodevelopmental disorders and disability. Research designed to ameliorate neurodevelopmental disorders in low- and middle-income countries, as well as globally, will benefit enormously from the ongoing advances in understanding their genetic and epigenetic causes, as modified by environment and culture. We provide examples of advances in the prevention and treatment of, and the rehabilitation of those with, neurodevelopment disorders in low- and middle-income countries, along with opportunities for further strategic research initiatives. Our examples are not the only possibilities for strategic research, but they illustrate problems that, when solved, could have a considerable impact in low-resource settings. In each instance, research in low- and middle-income countries led to innovations in identification, surveillance and treatment of a neurodevelopmental disorder. These innovations have also been integrated with genotypic mapping of neurodevelopmental disorders, forming important preventative and rehabilitative interventions with the potential for high impact. These advances will ultimately allow us to understand how epigenetic influences shape neurodevelopmental risk and resilience over time and across populations. Clearly, the most strategic areas of research opportunity involve cross-disciplinary integration at the intersection between the environment, brain or behaviour neurodevelopment, and genetic and epigenetic science. At these junctions a robust integrative cross-disciplinary scientific approach is catalysing the creation of technologies and interventions for old problems. Such approaches will enable us to achieve and sustain the United Nations moral and legal mandate for

  13. Eyeblink conditioning: a non-invasive biomarker for neurodevelopmental disorders.

    PubMed

    Reeb-Sutherland, Bethany C; Fox, Nathan A

    2015-02-01

    Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition, abnormalities in the cerebellum, a region of the brain highly involved in EBC, have been implicated in a number of neurodevelopmental disorders including autism spectrum disorders (ASDs). In the current paper, we review studies that have employed EBC as a biomarker for several neurodevelopmental disorders including fetal alcohol syndrome, Down syndrome, fragile X syndrome, attention deficit/hyperactivity disorder, dyslexia, specific language impairment, and schizophrenia. In addition, we discuss the benefits of using such a tool in individuals with ASD. PMID:23942847

  14. Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders

    PubMed Central

    Poot, Martin

    2015-01-01

    Based on genomic rearrangements and copy number variations, the contactin-associated protein-like 2 gene (CNTNAP2) has been implicated in neurodevelopmental disorders such as Gilles de la Tourette syndrome, intellectual disability, obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, and attention deficit hyperactivity disorder. To explain the phenotypic pleiotropy of CNTNAP2 alterations, several hypotheses have been put forward. Those include gene disruption, loss of a gene copy by a heterozygous deletion, altered regulation of gene expression due to loss of transcription factor binding and DNA methylation sites, and mutations in the amino acid sequence of the encoded protein which may provoke altered interactions of the CNTNAP2-encoded protein, Caspr2, with other proteins. Also exome sequencing, which covers <0.2% of the CNTNAP2 genomic DNA, has revealed numerous single nucleotide variants in healthy individuals and in patients with neurodevelopmental disorders. In some of these disorders, disruption of CNTNAP2 may be interpreted as a susceptibility factor rather than a directly causative mutation. In addition to being associated with impaired development of language, CNTNAP2 may turn out to be a central node in the molecular networks controlling neurodevelopment. This review discusses the impact of CNTNAP2 mutations on its functioning at multiple levels of the combinatorial genetic networks that govern brain development. In addition, recommendations for genomic testing in the context of clinical genetic management of patients with neurodevelopmental disorders and their families are put forward. PMID:25852443

  15. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

    PubMed

    Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

    2013-12-19

    Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders. PMID:24315484

  16. Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders

    PubMed Central

    Rossignol, E.

    2011-01-01

    A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders. PMID:21876820

  17. Sickle Cell Disease as a Neurodevelopmental Disorder

    ERIC Educational Resources Information Center

    Schatz, Jeffrey; McClellan, Catherine B.

    2006-01-01

    Sickle cell disease (SCD) is a blood disorder; however, the central nervous system (CNS) is one of the organs frequently affected by the disease. Brain disease can begin early in life and often leads to neurocognitive dysfunction. Approximately one-fourth to one-third of children with SCD have some form of CNS effects from the disease, which…

  18. Global metabolic profiling for the study of alcohol-related disorders.

    PubMed

    Gika, Helen G; Wilson, Ian D

    2014-01-01

    Alcohol-related disorders are multifaceted since ethanol can induce profound metabolic perturbations when taken in excess. Global metabolic profiling strategies may aid the understanding of ethanol-related effects by shedding light on these metabolic changes and potentially revealing unknown mechanisms of ethanol toxicity. Here an overview of studies designed to explore the effects of alcohol (ethanol) consumption using holistic metabolite profiling approaches (metabonomics/metabolomics) is presented, demonstrating the potential of this methodology. The analytical technologies used (NMR, GC-MS and LC-MS), have been applied to the profiling of serum, plasma, urine and tissues, obtained from animal models or humans, after exposure to alcohol. From the metabolic profiling data of a range of biological samples, a number of endogenous metabolites have been proposed as potential ethanol consumption-related biomarkers. The biomarkers suggested by these studies, and the biochemical insights that they provide for understanding the effects of ethanol mechanisms of toxicity, are discussed. PMID:24341495

  19. Childhood neurodevelopmental disorders and violent criminality: a sibling control study.

    PubMed

    Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul

    2014-11-01

    The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all child and adolescent mental health services in Stockholm, we identified 3,391 children, born 1984-1994, with neurodevelopmental disorders, and compared their risk for subsequent violent criminality with matched controls. Individuals with ADHD or TDs were at elevated risk of committing violent crimes, no such association could be seen for ASDs or OCD. ADHD and TDs are risk factors for subsequent violent criminality, while ASDs and OCD are not associated with violent criminality. PMID:23807203

  20. Exploring the Relationship between Experiential Avoidance, Alcohol Use Disorders, and Alcohol-Related Problems among First-Year College Students

    ERIC Educational Resources Information Center

    Levin, Michael E.; Lillis, Jason; Seeley, John; Hayes, Steven C.; Pistorello, Jacqueline; Biglan, Anthony

    2012-01-01

    Objective: This study explored the relationship of experiential avoidance (eg, the tendency to avoid, suppress, or otherwise control internal experiences even when doing so causes behavioral harm) to alcohol use disorders and alcohol-related problems. Participants: Cross-sectional data were collected from 240 undergraduate college students in…

  1. Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders

    PubMed Central

    Parikshak, Neelroop N.; Gandal, Michael J.; Geschwind, Daniel H.

    2015-01-01

    Genetic and genomic approaches have implicated hundreds of genetic loci in neurodevelopmental disorders and neurodegeneration, but mechanistic understanding continues to lag behind the pace of gene discovery. Understanding the role of specific genetic variants in the brain involves dissecting a functional hierarchy that encompasses molecular pathways, diverse cell types, neural circuits and, ultimately, cognition and behaviour. With a focus on transcriptomics, this Review discusses how high-throughput molecular, integrative and network approaches inform disease biology by placing human genetics in a molecular systems and neurobiological context. We provide a framework for interpreting network biology studies and leveraging big genomics data sets in neurobiology. PMID:26149713

  2. "Too Withdrawn" or "Too Friendly": Considering Social Vulnerability in Two Neuro-Developmental Disorders

    ERIC Educational Resources Information Center

    Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.

    2012-01-01

    In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neuro-developmental disorders Williams syndrome, characterised by "hypersociability", and autism spectrum disorders, characterised by "social…

  3. Adaptive profiles in autism and other neurodevelopmental disorders.

    PubMed

    Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar

    2015-04-01

    We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale (VABS) in communication, daily living skills, socialization and adaptive behaviour composite. Pearson-correlation analysis was performed between each domain of VABS and Full-Scale, Verbal and Performance IQ, and chronological age (CA). Results indicated that impairment in adaptive behaviour within the domain of socialization skills remains a distinctive factor of ASD versus OND, independently of intellectual disability (ID). Co-occurring ID result in further debilitating effects on overall functioning, especially in ASD. CA is negatively associated with VABS scores. PMID:25241010

  4. Intellectual Profiles in the Autism Spectrum and Other Neurodevelopmental Disorders.

    PubMed

    Mouga, Susana; Café, Cátia; Almeida, Joana; Marques, Carla; Duque, Frederico; Oliveira, Guiomar

    2016-09-01

    The influence of specific autism spectrum disorder (ASD) deficits in Intelligence Quotients (IQ), Indexes and subtests from the Wechsler Intelligence Scale for Children-III was investigated in 445 school-aged children: ASD (N = 224) and other neurodevelopmental disorders (N = 221), matched by Full-Scale IQ and chronological age. ASD have lower scores in the VIQ than PIQ. The core distinctive scores between groups are Processing Speed Index and "Comprehension" and "Coding" subtests with lower results in ASD. ASD group with normal/high IQ showed highest score on "Similarities" subtest whereas the lower IQ group performed better on "Object Assembly". The results replicated our previous work on adaptive behaviour, showing that adaptive functioning is positively correlated with intellectual profile, especially with the Communication domain in ASD. PMID:27312715

  5. Parenting stress among parents of children with Neurodevelopmental Disorders.

    PubMed

    Craig, Francesco; Operto, Francesca Felicia; De Giacomo, Andrea; Margari, Lucia; Frolli, Alessandro; Conson, Massimiliano; Ivagnes, Sara; Monaco, Marianna; Margari, Francesco

    2016-08-30

    In recent years, studies have shown that parents of children with Neurodevelopmental Disorders (NDDs) experience more parenting stress than parents of typically developing children, but the relation between the type of disorders and parenting stress is far from clear. The purpose of this study was to compare the parenting stress experienced by parents of 239 children with Specific Learning Disorders (SpLD), Language Disorders (LD), Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and typical development (TD). Parents of children with NDDs experience more parenting stress than those of children who have TD. Although, parents of children with ASD or ADHD report the most high scores of parenting stress, also the parents of children with SpLD or LD report higher parental stress compared with parent of children without NDDs. Another interesting finding was that IQ level or emotional and behavioral problems are associated with the higher levels of parenting stress. This study suggest that parent, both mothers and fathers, of children with different type of NDDs should be provided with interventions and resources to empower them with the knowledge and skills to reduce their stress and to enhance their quality of life. PMID:27280521

  6. Molecular mechanisms underlying neurodevelopmental disorders, ADHD and autism.

    PubMed

    Bădescu, George Mihai; Fîlfan, Mădălina; Sandu, Raluca Elena; Surugiu, Roxana; Ciobanu, Ovidiu; Popa-Wagner, Aurel

    2016-01-01

    Neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism represent a significant economic burden, which justify vigorous research to uncover its genetics and developmental clinics for a diagnostic workup. The urgency of addressing attention deficit hyperactivity disorder comorbidities is seen in the chilling fact that attention deficit hyperactivity disorder (ADHD), mood disorders, substance use disorders and obesity each increase the risk for mortality. However, data about comorbidity is mainly descriptive, with mechanistic studies limited to genetic epidemiological studies that document shared genetic risk factors among these conditions. Autism and intellectual disability affects 1.5 to 2% of the population in Western countries with many individuals displaying social-emotional agnosia and having difficulty in forming attachments and relationships. Underlying mechanisms include: (i) dysfunctions of neuronal miRNAs; (ii) deletions in the chromosome 21, subtelomeric deletions, duplications and a maternally inherited duplication of the chromosomal region 15q11-q13; (iii) microdeletions in on the long (q) arm of the chromosome in a region designated q21.1 increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems associated with autism, schizophrenia, and epilepsy and weak muscle tone (hypotonia); (iv) interstitial duplications encompassing 16p13.11. PMID:27516006

  7. An Open Conversation on Using Eye-Gaze Methods in Studies of Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Venker, Courtney E.; Kover, Sara T.

    2015-01-01

    Purpose: Eye-gaze methods have the potential to advance the study of neurodevelopmental disorders. Despite their increasing use, challenges arise in using these methods with individuals with neurodevelopmental disorders and in reporting sufficient methodological detail such that the resulting research is replicable and interpretable. Method: This…

  8. Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

    PubMed

    Bruining, Hilgo; Passtoors, Laurien; Goriounova, Natalia; Jansen, Floor; Hakvoort, Britt; de Jonge, Maretha; Poil, Simon-Shlomo

    2015-08-01

    The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking. We hypothesized that a paradoxical response to GABA-enforcing agents such as benzodiazepines may predict the efficacy of bumetanide treatment in neurodevelopmental disorders. We describe a case of a 10-year-old girl with ASD, epilepsy, cortical dysplasia, and a 15q11.2 duplication who had exhibited marked behavioral arousal after previous treatment with clobazam, a benzodiazepine. We hypothesized that this response indicated the presence of depolarizing excitatory GABA and started bumetanide treatment with monitoring of behavior, cognition, and EEG. The treatment resulted in a marked clinical improvement in sensory behaviors, rigidity, and memory performance, which was substantiated by questionnaires and cognitive assessments. At baseline, the girl's EEG showed a depression in absolute α power, an electrographic sign previously related to ASD, which was normalized with bumetanide treatment. The effects of bumetanide on cognition and EEG seemed to mirror the "nonparadoxical" responses to benzodiazepines in healthy subjects. In addition, temporal lobe epilepsy and cortical dysplasia have both been linked to disturbed chloride homeostasis and seem to support our assumption that the observed paradoxical response was due to GABA-mediated excitation. This case highlights that a paradoxical behavioral response to GABA-enforcing drugs may constitute a framework for targeted treatment with bumetanide. PMID:26216321

  9. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    PubMed Central

    López, Alberto J.; Wood, Marcelo A.

    2015-01-01

    It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development. PMID:25954173

  10. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders.

    PubMed

    López, Alberto J; Wood, Marcelo A

    2015-01-01

    It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development. PMID:25954173

  11. Difference or Disorder? Cultural Issues in Understanding Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Norbury, Courtenay Frazier; Sparks, Alison

    2013-01-01

    Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality…

  12. Epigenomic-basis of Preemptive Medicine for Neurodevelopmental Disorders.

    PubMed

    Kubota, Takeo; Miyake, Kunio; Hariya, Natsuyo; Mochizuki, Kazuki

    2015-06-01

    Neurodevelopmental disorders (NDs) are currently thought to be caused by either genetic defects or various environmental factors. Recent studies have demonstrated that congenital NDs can result not only from changes in DNA sequence in neuronal genes but also from changes to the secondary epigenomic modifications of DNA and histone proteins. Thus, epigenomic assays, as well as genomic assays, are currently performed for diagnosis of the congenital NDs. It is recently known that the epigenomic modifications can be altered by various environmental factors, which potentially cause acquired NDs. Furthermore these alterations can potentially be restored taking advantage of use of reversibility in epigenomics. Therefore, epigenome-based early diagnosis and subsequent intervention, by using drugs that restore epigenomic alterations, will open up a new era of preemptive medicine for congenital and acquired NDs. PMID:26069457

  13. Microbiota and neurodevelopmental windows: implications for brain disorders.

    PubMed

    Borre, Yuliya E; O'Keeffe, Gerard W; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2014-09-01

    Gut microbiota is essential to human health, playing a major role in the bidirectional communication between the gastrointestinal tract and the central nervous system. The microbiota undergoes a vigorous process of development throughout the lifespan and establishes its symbiotic rapport with the host early in life. Early life perturbations of the developing gut microbiota can impact neurodevelopment and potentially lead to adverse mental health outcomes later in life. This review compares the parallel early development of the intestinal microbiota and the nervous system. The concept of parallel and interacting microbial-neural critical windows opens new avenues for developing novel microbiota-modulating based therapeutic interventions in early life to combat neurodevelopmental deficits and brain disorders. PMID:24956966

  14. Epigenomic-basis of Preemptive Medicine for Neurodevelopmental Disorders

    PubMed Central

    Kubota, Takeo; Miyake, Kunio; Hariya, Natsuyo; Mochizuki, Kazuki

    2015-01-01

    Neurodevelopmental disorders (NDs) are currently thought to be caused by either genetic defects or various environmental factors. Recent studies have demonstrated that congenital NDs can result not only from changes in DNA sequence in neuronal genes but also from changes to the secondary epigenomic modifications of DNA and histone proteins. Thus, epigenomic assays, as well as genomic assays, are currently performed for diagnosis of the congenital NDs. It is recently known that the epigenomic modifications can be altered by various environmental factors, which potentially cause acquired NDs. Furthermore these alterations can potentially be restored taking advantage of use of reversibility in epigenomics. Therefore, epigenome-based early diagnosis and subsequent intervention, by using drugs that restore epigenomic alterations, will open up a new era of preemptive medicine for congenital and acquired NDs. PMID:26069457

  15. Relationship of attention-deficit/hyperactivity disorder symptom severity with severity of alcohol-related problems in a sample of inpatients with alcohol use disorder

    PubMed Central

    Bozkurt, Muge; Evren, Cuneyt; Umut, Gokhan; Evren, Bilge

    2016-01-01

    Purpose Attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to a higher risk of developing psychiatric problems such as depressive disorders, substance use disorder, and impulsivity. Adults who have comorbid ADHD and alcohol use disorder (AUD) are at greater risk of negative outcomes. Thus, it is important to evaluate the relationship of ADHD symptoms and the severity of alcohol-related problems among patients with AUD. The aim of the present study was to evaluate the effect of ADHD symptoms on severity of alcohol-related problems, while controlling the effects of depression and impulsivity in a sample of inpatients with AUD. Patients and methods Participants (n=190) were evaluated with the Beck Depression Inventory, the Short Form Barratt Impulsiveness Scale, the Michigan Alcohol Screening Test, and the Adult ADHD Self-Report Scale. Results Severity of the scale scores was positively correlated with each other. Although severity of depression and impulsivity (particularly non-planning impulsivity) predicted the severity of alcohol-related problems in a linear regression model, when severity of ADHD symptoms was included in the analysis, the inattentive subscale score, in particular, predicted the severity of alcohol-related problems together with non-planning impulsivity, whereas depression was no longer a predictor. Conclusion These findings suggest that, together with non-planning impulsivity, symptoms of ADHD (particularly inattentive factor) are an important factor that predict alcohol-related problems, while controlling the severity of depressive symptoms among inpatients with AUD. PMID:27462159

  16. Genes, Cognition, and Communication: Insights from Neurodevelopmental Disorders

    PubMed Central

    Bishop, DVM

    2009-01-01

    Twin and family studies have demonstrated that most cognitive traits are moderately to highly heritable. Neurodevelopmental disorders such as dyslexia, autism, and specific language impairment (SLI) also show strong genetic influence. Nevertheless, it has proved difficult for researchers to identify genes that would explain substantial amounts of variance in cognitive traits or disorders. Although this observation may seem paradoxical, it fits with a multifactorial model of how complex human traits are influenced by numerous genes that interact with one another, and with the environment, to produce a specific phenotype. Such a model can also explain why genetic influences on cognition have not vanished in the course of human evolution. Recent linkage and association studies of SLI and dyslexia are reviewed to illustrate these points. The role of nonheritable genetic mutations (sporadic copy number variants) in causing autism is also discussed. Finally, research on phenotypic correlates of allelic variation in the genes ASPM and microcephalin is considered; initial interest in these as genes for brain size or intelligence has been dampened by a failure to find phenotypic differences in people with different versions of these genes. There is a current vogue for investigators to include measures of allelic variants in studies of cognition and cognitive disorders. It is important to be aware that the effect sizes associated with these variants are typically small and hard to detect without extremely large sample sizes. PMID:19338500

  17. Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders

    PubMed Central

    Francis, S.M.; Sagar, A.; Levin-Decanini, T.; Liu, W.; Carter, C.S.; Jacob, S.

    2015-01-01

    Oxytocin (OT) and arginine vasopressin (AVP) are two small, related neuropeptide hormones found in many mammalian species, including humans. Dysregulation of these neuropeptides have been associated with changes in behavior, especially social interactions. We review how the OT and AVP systems have been investigated in Autism Spectrum Disorder (ASD), Prader–Willi Syndrome (PWS), Williams Syndrome (WS) and Fragile X syndrome (FXS). All of these neurodevelopmental disorders (NDD) are marked by social deficits. While PWS, WS and FXS have identified genetic mutations, ASD stems from multiple genes with complex interactions. Animal models of NDD are invaluable for studying the role and relatedness of OT and AVP in the developing brain. We present data from a FXS mouse model affecting the fragile X mental retardation 1 (Fmr1) gene, resulting in decreased OT and AVP staining cells in some brain regions. Reviewing the research about OT and AVP in these NDD suggests that altered OT pathways may be downstream from different etiological factors and perturbations in development. This has implications for ongoing studies of the therapeutic application of OT in NDD. PMID:24462936

  18. Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders.

    PubMed

    Francis, S M; Sagar, A; Levin-Decanini, T; Liu, W; Carter, C S; Jacob, S

    2014-09-11

    Oxytocin (OT) and arginine vasopressin (AVP) are two small, related neuropeptide hormones found in many mammalian species, including humans. Dysregulation of these neuropeptides have been associated with changes in behavior, especially social interactions. We review how the OT and AVP systems have been investigated in Autism Spectrum Disorder (ASD), Prader-Willi Syndrome (PWS), Williams Syndrome (WS) and Fragile X syndrome (FXS). All of these neurodevelopmental disorders (NDD) are marked by social deficits. While PWS, WS and FXS have identified genetic mutations, ASD stems from multiple genes with complex interactions. Animal models of NDD are invaluable for studying the role and relatedness of OT and AVP in the developing brain. We present data from a FXS mouse model affecting the fragile X mental retardation 1 (Fmr1) gene, resulting in decreased OT and AVP staining cells in some brain regions. Reviewing the research about OT and AVP in these NDD suggests that altered OT pathways may be downstream from different etiological factors and perturbations in development. This has implications for ongoing studies of the therapeutic application of OT in NDD. This article is part of a Special Issue entitled Oxytocin and Social Behav. PMID:24462936

  19. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders

    PubMed Central

    Schubert, D; Martens, G J M; Kolk, S M

    2015-01-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies. PMID:25450230

  20. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

    PubMed

    Schubert, D; Martens, G J M; Kolk, S M

    2015-07-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies. PMID:25450230

  1. Neurodevelopmental origins of bipolar disorder: iPSC models.

    PubMed

    O'Shea, K Sue; McInnis, Melvin G

    2016-06-01

    Bipolar disorder (BP) is a chronic neuropsychiatric condition characterized by pathological fluctuations in mood from mania to depression. Adoption, twin and family studies have consistently identified a significant hereditary component to BP, yet there is no clear genetic event or consistent neuropathology. BP has been suggested to have a developmental origin, although this hypothesis has been difficult to test since there are no viable neurons or glial cells to analyze, and research has relied largely on postmortem brain, behavioral and imaging studies, or has examined proxy tissues including saliva, olfactory epithelium and blood cells. Neurodevelopmental factors, particularly pathways related to nervous system development, cell migration, extracellular matrix, H3K4 methylation, and calcium signaling have been identified in large gene expression and GWAS studies as altered in BP. Recent advances in stem cell biology, particularly the ability to reprogram adult somatic tissues to a pluripotent state, now make it possible to interrogate these pathways in viable cell models. A number of induced pluripotent stem cell (iPSC) lines from BP patient and healthy control (C) individuals have been derived in several laboratories, and their ability to form cortical neurons examined. Early studies suggest differences in activity, calcium signaling, blocks to neuronal differentiation, and changes in neuronal, and possibly glial, lineage specification. Initial observations suggest that differentiation of BP patient-derived neurons to dorsal telencephalic derivatives may be impaired, possibly due to alterations in WNT, Hedgehog or Nodal pathway signaling. These investigations strongly support a developmental contribution to BP and identify novel pathways, mechanisms and opportunities for improved treatments. PMID:26608002

  2. Maturing insights into the genetic architecture of neurodevelopmental disorders - from common and rare variant interplay to precision psychiatry.

    PubMed

    Lesch, Klaus-Peter

    2016-06-01

    The categorisation of neurodevelopmental and psychiatric disorders by clinical syndromes, rather than by aetiology, continues to obstruct progress in biomarker identification as well as innovative drug development and effective treatment in general. There is a decisive move to think of neurodevelopmental disorders as a spectrum rather than discrete categorical entities. We might call them neurodevelopmental spectrum disorders (NSDs) ranging from intellectual disability (ID) to autism (ASD), and attention-deficit/hyperactivity disorder (ADHD) (Kiser, Rivero, & Lesch, ). PMID:27192951

  3. Chemosensory Dysfunction in Alcohol-Related Disorders: A Joint Exploration of Olfaction and Taste.

    PubMed

    Brion, Mélanie; de Timary, Philippe; Vander Stappen, Caroline; Guettat, Lamia; Lecomte, Benoît; Rombaux, Philippe; Maurage, Pierre

    2015-11-01

    Chemosensory (olfaction-taste) dysfunctions are considered as reliable biomarkers in many neurological and psychiatric states. However, experimental measures of chemosensory abilities are lacking in alcohol-dependence (AD) and Korsakoff Syndrome (KS, a neurological complication of AD), despite the role played by alcohol-related odors and taste in the emergence and maintenance of AD. This study thus investigated chemosensory impairments in AD and KS. Olfactory-gustatory measures were taken among 20 KS, 20 AD, and 20 control participants. Olfaction (odor detection-discrimination-identification) was assessed using the "Sniffin Sticks" battery and taste was measured using the "Taste Strips" task. Impairments were found for high-level olfaction in AD (odor discrimination) and KS (odor discrimination-identification), even after controlling for psychopathological comorbidities. Gustatory deficits were also observed in both groups, indexing a global deficit for chemosensory perception. Finally, the gradient of impairment between the successive disease stages for odor identification suggests that the hypothesis of a continuum between AD and KS regarding cognitive deficits can be generalized to chemosensory perception. AD and KS are thus characterized by deficits in chemosensory abilities, which could constitute a marker of the AD-KS transition. In view of its deleterious influence on everyday life, chemosensory dysfunction should also be taken into account in clinical settings. PMID:26354933

  4. Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

    PubMed Central

    Ibi, Daisuke; Yamada, Kiyofumi

    2015-01-01

    Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders. PMID:26633355

  5. Genes, Circuits, and Precision Therapies for Autism and Related Neurodevelopmental Disorders

    PubMed Central

    2016-01-01

    Research in genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. While the exact identity of many of the genes remains to be discovered, genes identified to date encode for proteins that play roles in certain conserved pathways: protein synthesis, transcriptional/epigenetic regulation and synaptic signaling. Next generation of research in neurodevelopmental disorders needs to address the neural circuitry underlying the behavioral symptoms and co-morbidities, the cell types playing critical roles in these circuits and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we are able to leverage the heterogeneity of neurodevelopmental disorders into precision medicine, will the mechanism-based therapeutics for these disorders start to unlock success. PMID:26472761

  6. Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders.

    PubMed

    Sahin, Mustafa; Sur, Mriganka

    2015-11-20

    Research in the genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. Although the exact identity of many of the genes remains to be discovered, genes identified to date encode proteins that play roles in certain conserved pathways: protein synthesis, transcriptional and epigenetic regulation, and synaptic signaling. The next generation of research in neurodevelopmental disorders must address the neural circuitry underlying the behavioral symptoms and comorbidities, the cell types playing critical roles in these circuits, and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we can leverage the heterogeneity of neurodevelopmental disorders into precision medicine will the mechanism-based therapeutics for these disorders start to unlock success. PMID:26472761

  7. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis.

    PubMed

    Gillberg, I Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

    2016-01-01

    We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had never met criteria for an additional psychiatric/neurodevelopmental diagnosis and more than half had ongoing comorbidity (most commonly either ADHD or depression or both). Any psychiatric comorbidity increased the risk of poorer outcome. The minority of the AS group who no longer met criteria for a full diagnosis of an autism spectrum disorder were usually free of current psychiatric comorbidity. The high rate of psychiatric/neurodevelopmental comorbidities underscores the need for a full psychiatric/neurodevelopmental assessment at follow-up of males with AS. PMID:26210519

  8. Neurodevelopmental Disorders in Low- and Middle-Income Countries

    ERIC Educational Resources Information Center

    Newton, Charles R.

    2012-01-01

    In "Global Perspective on Early Diagnosis and Intervention for Children with Developmental Delays and Disabilities" (p1079-1084, this issue), Scherzer et al. highlighted the potential increase in neurodevelopmental impairments and disabilities affecting an increasing number of children in low- and middle-income countries (LMIC). In this…

  9. Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders

    PubMed Central

    Vallianatos, Christina N; Iwase, Shigeki

    2015-01-01

    MethylationofhistoneH3lysine4(H3K4me)isanintricatelyregulatedposttranslational modification, which is broadly associated with enhancers and promoters of actively transcribed genomic loci. Recent advances in next-generation sequencing have identified a number of H3K4me regulators mutated in neurodevelopmental disorders including intellectual disabilities, autism spectrum disorders, and schizophrenia. Here, we aim to summarize the molecular function of H3K4me-regulating enzymes in brain development and function. We describe four H3K4me methyltransferases (KMT2A, KMT2C, KMT2D, KMT2F), four demethylases (KDM1A, KDM5A, KDM5B, KDM5C), and two reader proteins (PHF21A, PHF8) mutated in neurodevelopmental disorders. Understanding the role of these chromatin regulators in the development and maintenance of neural connections will advance therapeutic opportunities for prevention and treatment of these lifelong neurodevelopmental disorders. PMID:26077434

  10. Screening for substance use disorders in neurodevelopmental disorders: a clinical routine?

    PubMed

    Palmqvist, Margita; Edman, Gunnar; Bölte, Sven

    2014-05-01

    Evidence suggests that substance use disorders (SUD) tend to be underdiagnosed in psychiatry. The objective of this study was to investigate whether drug and alcohol screening is a clinical routine in the assessment of two prominent neurodevelopmental disorders, namely ADHD and autism spectrum disorder (ASD). We surveyed drug and alcohol screening routines in 34 general child and adolescent (only practice for adolescents, not children, was assessed) and 29 adult psychiatric outpatient departments in Stockholm County, Sweden. Structured telephone interviews mapping SUD screening procedures were conducted with department representatives in charge. Only a minority of child and adolescent departments regularly used SUD screening questionnaires (6 %) in ADHD and ASD assessment, while this was more common in adult psychiatry (55 %). Urine/blood-based toxicology tests were always used in 28 % and sometimes or in case of clinical suspicion in 38 % of the adult units. Such tests were used sometimes or in case of clinical suspicion in 15 % of the child psychiatric departments, but never routinely. Findings reveal that screening for SUD in ADHD and ASD is not an integral part of routine clinical assessments in psychiatry, although increasingly an integral part of many clinical guidelines. Thus, SUD might be underdiagnosed in neurodevelopmental disorders, which could be particularly true for child and adolescent psychiatry settings. PMID:23949101

  11. Adaptation of the "Ten Questions" to Screen for Autism and other Neurodevelopmental Disorders in Uganda

    ERIC Educational Resources Information Center

    Kakooza-Mwesige, Angelina; Ssebyala, Keron; Karamagi, Charles; Kiguli, Sarah; Smith, Karen; Anderson, Meredith C.; Croen, Lisa A.; Trevathan, Edwin; Hansen, Robin; Smith, Daniel; Grether, Judith K.

    2014-01-01

    Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener…

  12. Neurobiological Circuits Regulating Attention, Cognitive Control, Motivation, and Emotion: Disruptions in Neurodevelopmental Psychiatric Disorders

    ERIC Educational Resources Information Center

    Arnsten, Amy F. T.; Rubia, Katya

    2012-01-01

    Objective: This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Method: Studies of animals,…

  13. Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins

    PubMed Central

    2013-01-01

    Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders. PMID:23425632

  14. Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins.

    PubMed

    Li, Junlin; Zhao, Guifang; Gao, Xiaocai

    2013-01-01

    Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders. PMID:23425632

  15. The "neuro" of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder.

    PubMed

    Ratner, Nancy; Brodeur, Garrett M; Dale, Russell C; Schor, Nina F

    2016-07-01

    Neuroblastoma is a childhood cancer derived from cells of neural crest origin. The hallmarks of its enigmatic character include its propensity for spontaneous regression under some circumstances and its association with paraneoplastic opsoclonus, myoclonus, and ataxia. The neurodevelopmental underpinnings of its origins may provide important clues for development of novel therapeutic and preventive agents for this frequently fatal malignancy and for the associated paraneoplastic syndromes. Ann Neurol 2016;80:13-23. PMID:27043043

  16. APPEARANCE OF NEURODEVELOPMENTAL DISORDERS IN CHILDREN DELIVERED POST-TERM: A CROSS-SECTION STUDY

    PubMed Central

    Vukojevic, Mladenka; Trninic, Ines; Dodaj, Arta; Malenica, Masa; Barisic, Tatjana; Stojic, Sandra

    2016-01-01

    Goal: To analyze the appearance of neurodevelopmental disorders in children delivered post-term and to find out whether prolonged pregnancy may be a cause of such disorders in a selected group participants. Patients and methods: This study included a cohort of 34 children born post-term suffering from neurodevelopmental disorders who were treated at the Service for psycho-physiological and speaking disorders in Mostar, Bosnia and Herzegovina during an 18-year period. Results: There were 59.4% of male and 40.6% female patients (P=0.002). The most common neurodevelopmental disorder in the sample was intellectual disability (38.2%), followed by epilepsy (26.4%), delayed psychomotor development (14.7%), and cerebral palsy (11.7%) (P<0.001). The correlation between mothers’ parity and post-term delivery was found (P=0.016). Conclusion: Post-term delivery may be the cause of neurodevelopmental disorders. The most common disorder among them were intellectual difficulties. PMID:27147913

  17. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

    EPA Science Inventory

    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  18. Neurodevelopmental Disorders (ASD and ADHD): DSM-5, ICD-10, and ICD-11.

    PubMed

    Doernberg, Ellen; Hollander, Eric

    2016-08-01

    Neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have undergone considerable diagnostic evolution in the past decade. In the United States, the current system in place is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), whereas worldwide, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) serves as a general medical system. This review will examine the differences in neurodevelopmental disorders between these two systems. First, we will review the important revisions made from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) to the DSM-5, with respect to ASD and ADHD. Next, we will cover the similarities and differences between ASD and ADHD classification in the DSM-5 and the ICD-10, and how these differences may have an effect on neurodevelopmental disorder diagnostics and classification. By examining the changes made for the DSM-5 in 2013, and critiquing the current ICD-10 system, we can help to anticipate and advise on the upcoming ICD-11, due to come online in 2017. Overall, this review serves to highlight the importance of progress towards complementary diagnostic classification systems, keeping in mind the difference in tradition and purpose of the DSM and the ICD, and that these systems are dynamic and changing as more is learned about neurodevelopmental disorders and their underlying etiology. Finally this review will discuss alternative diagnostic approaches, such as the Research Domain Criteria (RDoC) initiative, which links symptom domains to underlying biological and neurological mechanisms. The incorporation of new diagnostic directions could have a great effect on treatment development and insurance coverage for neurodevelopmental disorders worldwide. PMID:27364515

  19. Seroprevalence of Toxoplasma gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt.

    PubMed

    Shehata, Amany I; Hassanein, Faika I; Abdul-Ghani, Rashad

    2016-02-01

    Toxoplasma gondii is an opportunistic parasite with neurotropic characteristics that can mediate neurodevelopmental disorders, including mental, behavioral and personality aspects of their hosts. Therefore, the seroprevalence of anti-Toxoplasma antibodies has been studied in patients with different neurological disorders from different localities. On searching online databases, however, we could not find published studies on the seroprevalence of anti-Toxoplasma antibodies among patients with neurodevelopmental disorders in Egypt. Therefore, the present preliminary study was conducted to determine the serological profile of T. gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt. Data and blood samples were collected from 188 patients recruited for the study from four mental rehabilitation centers in the period from July 2014 to March 2015. The overall seropositivity rates of IgM and IgG among patients were 16.5% (31/188) and 50.0% (94/188), respectively. Of the studied patients' characteristics, only age was significantly associated with anti-Toxoplasma IgG seropositivity, with older patients being about twice more likely exposed to infection. However, no statistically significant association was found with IgM. In addition, seropositivity of anti-Toxoplasma IgG, but not IgM, was significantly associated with non-schizophrenic neurodevelopmental disorders; however, neither IgG nor IgM showed a significant association with cognitive impairment as indicated by the intelligence quotient scores. PMID:26656562

  20. Childhood Neurodevelopmental Disorders and Violent Criminality: A Sibling Control Study

    ERIC Educational Resources Information Center

    Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul

    2014-01-01

    The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all…

  1. Neurodevelopmental Disorders in Children with Severe to Profound Sensorineural Hearing Loss: A Clinical Study

    ERIC Educational Resources Information Center

    Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni

    2010-01-01

    Aim: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation…

  2. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    PubMed Central

    2012-01-01

    This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies. PMID:22958744

  3. Management of Sleep Disorders in Children With Neurodevelopmental Disorders: A Review.

    PubMed

    Blackmer, Allison Beck; Feinstein, James A

    2016-01-01

    Neurodevelopmental disorders (NDDs) are defined as a group of disorders caused by changes in early brain development, resulting in behavioral and cognitive alterations in sensory and motor systems, speech, and language. NDDs affect approximately 1-2% of the general population. Up to 80% of children with NDDs are reported to have disrupted sleep; subsequent deleterious effects on daytime behaviors, cognition, growth, and overall development of the child are commonly reported. Examples of NDDs discussed in this review include autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome. The etiology of sleep disorders in children with NDDs is largely heterogeneous and disease specific. The diagnosis and management of sleep disorders in this population are complex, and little high-quality data exist to guide a consistent approach to therapy. Managing sleep disorders in children with NDDs is critical both for the child and for the family but is often frustrating due to the refractory nature of the problem. Sleep hygiene must be implemented as first-line therapy; if sleep hygiene alone fails, it should be combined with pharmacologic management. The available evidence for the use of common pharmacologic interventions, such as iron supplementation and melatonin, as well as less common interventions, such as melatonin receptor agonists, clonidine, gabapentin, hypnotics, trazodone, and atypical antipsychotics is reviewed. Further, parents and caregivers should be provided with appropriate education on the nature of the sleep disorders and the expectation for modest pharmacologic benefit, at best. Additional data from well-designed trials in children with NDDs are desperately needed to gain a better understanding of sleep pharmacotherapy including efficacy and safety implications. Until then, clinicians must rely on the limited available data, as well as clinical expertise, when managing sleep disorders in the

  4. [The amygdala and its relation to autism, behavioural disorders and other neurodevelopmental disorders].

    PubMed

    Ruggieri, Víctor L

    2014-02-24

    The amygdala is related with the recognition of the emotional meaning of stimuli, long-term memory, the orientation of social stimuli and the perception of gaze orientation. It plays a fundamental role in the recognition of faces, especially those expressing fear, and makes it possible to comprehend different emotional states, which will facilitate an appropriate social cognition. Dysfunctions of the amygdala have been associated to a number of different neurodevelopmental disorders as well as neurocognitive and behavioural disorders in specific neurogenetic entities. A number of studies focused on the amygdalic complex have allowed researchers to understand many pathophysiological aspects and to formulate new hypotheses regarding their origins. Given that the disorders or conditions in which the role of the amygdala has been evoked are becoming increasingly more extensive, this article refers the reader to those that have aroused the most interest in recent years. Thus, they can be divided into two groups: developmental and behavioural disorders (autism, anxiety disorders, bipolar disorder, alexithymia and anorexia nervosa) and specific neurogenetic entities (fragile X, Rett, Prader-Willi and Williams syndromes), in which structural or dysfunctional alterations have been observed that may be related with their neurocognitive and behavioural symptoms. It is important to remember that the amygdala is a highly connected structure that forms truly functional networks and has been associated to different disorders with varied explanations and includes several different pathophysiological phenomena. Its role must not, therefore, be simplified in a reductionistic manner, but also placed upon a hierarchy of dysfunctions in other areas that interact with it. PMID:25252660

  5. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years after Initial Diagnosis

    ERIC Educational Resources Information Center

    Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

    2016-01-01

    We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had "never" met criteria for an additional psychiatric/neurodevelopmental diagnosis and…

  6. Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming.

    PubMed

    Wade, Mark; Prime, Heather; Madigan, Sheri

    2015-01-01

    Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders-autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)-to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment. PMID:26258141

  7. Impairments in dendrite morphogenesis as etiology for neurodevelopmental disorders and implications for therapeutic treatments.

    PubMed

    Copf, Tijana

    2016-09-01

    Dendrite morphology is pivotal for neural circuitry functioning. While the causative relationship between small-scale dendrite morphological abnormalities (shape, density of dendritic spines) and neurodevelopmental disorders is well established, such relationship remains elusive for larger-scale dendrite morphological impairments (size, shape, branching pattern of dendritic trees). Here, we summarize published data on dendrite morphological irregularities in human patients and animal models for neurodevelopmental disorders, with focus on autism and schizophrenia. We next discuss high-risk genes for these disorders and their role in dendrite morphogenesis. We finally overview recent developments in therapeutic attempts and we discuss how they relate to dendrite morphology. We find that both autism and schizophrenia are accompanied by dendritic arbor morphological irregularities, and that majority of their high-risk genes regulate dendrite morphogenesis. Thus, we present a compelling argument that, along with smaller-scale morphological impairments in dendrites (spines and synapse), irregularities in larger-scale dendrite morphology (arbor shape, size) may be an important part of neurodevelopmental disorders' etiology. We suggest that this should not be ignored when developing future therapeutic treatments. PMID:27143622

  8. Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders

    PubMed Central

    DENNIS, MAUREEN; FRANCIS, DAVID J.; CIRINO, PAUL T.; SCHACHAR, RUSSELL; BARNES, MARCIA A.; FLETCHER, JACK M.

    2011-01-01

    IQ scores are volatile indices of global functional outcome, the final common path of an individual’s genes, biology, cognition, education, and experiences. In studying neurocognitive outcomes in children with neurodevelopmental disorders, it is commonly assumed that IQ can and should be partialed out of statistical relations or used as a covariate for specific measures of cognitive outcome. We propose that it is misguided and generally unjustified to attempt to control for IQ differences by matching procedures or, more commonly, by using IQ scores as covariates. We offer logical, statistical, and methodological arguments, with examples from three neurodevelopmental disorders (spina bifida meningomyelocele, learning disabilities, and attention deficit hyperactivity disorder) that: (1) a historical reification of general intelligence, g, as a causal construct that measures aptitude and potential rather than achievement and performance has fostered the idea that IQ has special status and that in studying neurocognitive function in neurodevelopmental disorders; (2) IQ does not meet the requirements for a covariate; and (3) using IQ as a matching variable or covariate has produced overcorrected, anomalous, and counterintuitive findings about neurocognitive function. PMID:19402919

  9. Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

    PubMed Central

    Wade, Mark; Prime, Heather; Madigan, Sheri

    2015-01-01

    Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment. PMID:26258141

  10. Sleep Disturbances in Individuals with Alcohol-Related Disorders: A Review of Cognitive-Behavioral Therapy for Insomnia (CBT-I) and Associated Non-Pharmacological Therapies

    PubMed Central

    Brooks, Alyssa T; Wallen, Gwenyth R

    2014-01-01

    Sleep disturbances are common among alcohol-dependent individuals and are often associated with relapse. The utility of behavioral therapies for sleep disturbances, including cognitive-behavioral therapy for insomnia (CBT-I), among those with alcohol-related disorders is not well understood. This review systematically evaluates the evidence of CBT-I and related behavioral therapies applied to those with alcohol-related disorders and accompanying sleep disturbances. A search of four research databases (PubMed, PsycINFO, Embase, and CINAHL Plus) yielded six studies that met selection criteria. Articles were reviewed using Cochrane’s Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) scoring system. A majority of the studies demonstrated significant improvements in sleep efficiency among behavioral therapy treatment group(s), including but not limited to CBT-I. While behavioral sleep interventions have been successful in varied populations, they may not be utilized to their full potential among those with alcohol-related disorders as evidenced by the low number of studies found. These findings suggest a need for mixed-methods research on individuals’ sleep experience to inform interventions that are acceptable to the target population. PMID:25288884

  11. Spatiotemporal Molecular Approach of in utero Electroporation to Functionally Decipher Endophenotypes in Neurodevelopmental Disorders

    PubMed Central

    Kolk, Sharon Margriet; de Mooij-Malsen, Annetrude Johanne; Martens, Gerard Julianus Maria

    2011-01-01

    We have only just begun to decipher the complexity of our brain, including its maturation. Correct brain development and communication among brain areas are crucial for proper cognitive behavior. Brain area-specific genes expressed within a particular time window direct neurodevelopmental events such as proliferation, migration, axon guidance, dendritic arborization, and synaptogenesis. These genes can pose as susceptibility factors in neurodevelopmental disorders eventually resulting in area-specific cognitive deficits. Therefore, in utero electroporation (IUE)-mediated gene transfer can aid in creating valuable animal models in which the regionality and time of expression can be restricted for the targeted gene(s). Moreover, through the use of cell-type-specific molecular constructs, expression can be altered in a particular neuronal subset within a distinct area such that we are now able to causally link the function of that gene in that brain region to the etiology of the disorder. Thus, IUE-mediated gene transfer is an attractive molecular technique to spatiotemporally address the developmental aspects of gene function in relation to neurodevelopmental disorder-associated endophenotypes. PMID:22065947

  12. Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models.

    PubMed

    Homberg, Judith R; Kyzar, Evan J; Nguyen, Michael; Norton, William H; Pittman, Julian; Poudel, Manoj K; Gaikwad, Siddharth; Nakamura, Shun; Koshiba, Mamiko; Yamanouchi, Hideo; Scattoni, Maria Luisa; Ullman, Jeremy F P; Diamond, David M; Kaluyeva, Aleksandra A; Parker, Matthew O; Klimenko, Victor M; Apryatin, Sergey A; Brown, Richard E; Song, Cai; Gainetdinov, Raul R; Gottesman, Irving I; Kalueff, Allan V

    2016-06-01

    Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and migration, synapse formation and myelination, aberrant neural development occurs over a substantial period of time. Genetic, epigenetic, and environmental factors play a key role in NDD pathogenesis. Animal models are an indispensable tool to study NDDs. Paralleling clinical findings, we comprehensively evaluate various preclinical tests and models which target key (social, cognitive, motor) neurobehavioral domains of ASD and other common NDDs. Covering both traditional (rodent) and alternative NDD models, we outline the emerging areas of research and emphasize how preclinical models play a key role in gaining translational and mechanistic insights into NDDs and their therapy. PMID:27048961

  13. Teaching Students with Developmental Disabilities: Tips from Teens and Young Adults with Fetal Alcohol Spectrum Disorder

    ERIC Educational Resources Information Center

    Duquette, Cheryll; Stodel, Emma; Fullarton, Stephanie; Hagglund, Karras

    2006-01-01

    Fetal Alcohol Spectrum Disorder (FASD) is a term that encompasses the various neurodevelopmental disorders experienced by individuals with prenatal alcohol exposure. FASD incorporates the terms Fetal Alcohol Syndrome (FAS), Fetal Alcohol Effects (FAE), and Alcohol-Related Neurodevelopmental Disorder (ARND). Early studies showed that students with…

  14. Elevated titanium levels in Iraqi children with neurodevelopmental disorders echo findings in occupation soldiers.

    PubMed

    Savabieasfahani, M; Alaani, S; Tafash, M; Dastgiri, S; Al-Sabbak, M

    2015-01-01

    Anthropogenic release of pollutants into the environment is especially harmful to growing fetuses and young children. These populations are at an increased risk of damage because exposure to pollutants during critical periods of development can cause many impairments. Children's exposure to mixtures of metals could be responsible for the rising numbers of neurological disorders surfacing in Iraqi children. Titanium (Ti) and magnesium (Mg) are heavily used in war industries. Exposure to Ti and Mg has been linked to the dust in occupation soldiers' lungs. Hair samples of children in Hawija, Iraq (n = 13) contained significantly higher levels of Ti compared to Iranian children (n = 13) living near the Iraqi border (2080 ± 940 vs 707 ± 421 μg/kg, p < 0.0001). Magnesium was 1.7 times higher in Hawija children compared to Iranian children (115,763 ± 118,155 vs 67,650 ± 46,729 μg/kg). In samples from Hawija, Ti was 1.3 times higher in children with neurodevelopmental disorders (2198 ± 1108 vs 1942 ± 779 μg/kg), and Mg was 1.9 times higher in children without neurodevelopmental disorders (155,618 ± 140,791 vs 81,602 ± 91,940 μg/kg). Lead, arsenic, and cadmium in Hawija children with neurodevelopmental disorders (n = 6) were 2.5, 2.2, and 1.37 times higher compared to non-disabled children (n = 7). To get a clear understanding of the current status of neurodevelopmental disorders in Iraqi children and to determine the magnitude of this suspected global health issue, registries should be set up to compile and aggregate data from hospitals, clinics, and health centers across the country. Functional registries can develop collaborations with researchers toward finding causes of these disorders in Iraqi children and toward preventing them. PMID:25446717

  15. Can ω-3 fatty acids and tocotrienol-rich vitamin E reduce symptoms of neurodevelopmental disorders?

    PubMed

    Gumpricht, Eric; Rockway, Susie

    2014-01-01

    The incidence of childhood neurodevelopmental disorders, which include autism, attention-deficit hyperactivity disorders, and apraxia, are increasing worldwide and have a profound effect on the behaviors, cognitive skills, mood, and self-esteem of these children. Although the etiologies of these disorders are unclear, they often accompany genetic and biochemical abnormalities resulting in cognitive and communication difficulties. Because cognitive and neural development require essential fatty acids (particularly long-chain ω-3 fatty acids often lacking in mother's and children's diets) during critical growth periods, the potential behavior-modifying effects of these fatty acids as "brain nutrients" has attracted considerable attention. Additionally, there is compelling evidence for increased oxidative stress, altered antioxidant defenses, and neuroinflammation in these children. The purpose of this review is to provide a scientific rationale based on cellular, experimental animal model, observational, and clinical intervention studies for incorporating the combination of ω-3 fatty acids and tocotrienol-rich vitamin E as complementary nutritional therapies in children with neurodevelopmental disorders. Should this nutritional combination correct key clinical or biochemical outcomes and/or improve behavioral patterns, it would provide a safe, complementary option for these children. PMID:24631384

  16. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

    PubMed

    Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G W; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F; Manchester, David; Boyer, Philip J; Manzur, Adnan Y; Lourenco, Charles Marques; Pilz, Daniela T; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K; Rogers, R Curtis; Ryan, Monique M; Brown, Natasha J; McLean, Catriona A; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz

    2016-03-01

    Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed

  17. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

    PubMed Central

    Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M.; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F.; Manchester, David; Boyer, Philip J.; Manzur, Adnan Y.; Lourenco, Charles Marques; Pilz, Daniela T.; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K.; Rogers, R. Curtis; Ryan, Monique M.; Brown, Natasha J.; McLean, Catriona A.; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A.; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias

    2016-01-01

    Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed

  18. The Developmental Transcriptome of the Human Brain: Implications for Neurodevelopmental Disorders

    PubMed Central

    Tebbenkamp, Andrew T. N.; Willsey, A. Jeremy; State, Matthew W.; Šestan, Nenad

    2014-01-01

    Purpose of review Recent characterizations of the transcriptome of the developing human brain by several groups have generated comprehensive datasets on coding and noncoding RNAs that will be instrumental for illuminating the underlying biology of complex neurodevelopmental disorders. This review summarizes recent studies successfully utilizing these data to increase our understanding of the molecular mechanisms of pathogenesis. Recent findings Several approaches have successfully integrated developmental transcriptome data with gene discovery to generate testable hypotheses about when and where in the developing human brain disease-associated genes converge. Specifically, these include the projection neurons in the prefrontal and primary motor-somatosensory cortex during mid-fetal development in autism spectrum disorder and the frontal cortex during fetal development in schizophrenia. Summary Developmental transcriptome data is a key to interpreting disease-associated mutations and transcriptional changes. Novel approaches integrating the spatial and temporal dimensions of these data have increased our understanding of when and where pathology occurs. Refinement of spatial and temporal properties and expanding these findings to other neurodevelopmental disorders will provide critical insights for understanding disease biology. PMID:24565942

  19. A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders

    PubMed Central

    Reinhard, Sarah M.; Razak, Khaleel; Ethell, Iryna M.

    2015-01-01

    The extracellular matrix (ECM) is a critical regulator of neural network development and plasticity. As neuronal circuits develop, the ECM stabilizes synaptic contacts, while its cleavage has both permissive and active roles in the regulation of plasticity. Matrix metalloproteinase 9 (MMP-9) is a member of a large family of zinc-dependent endopeptidases that can cleave ECM and several cell surface receptors allowing for synaptic and circuit level reorganization. It is becoming increasingly clear that the regulated activity of MMP-9 is critical for central nervous system (CNS) development. In particular, MMP-9 has a role in the development of sensory circuits during early postnatal periods, called ‘critical periods.’ MMP-9 can regulate sensory-mediated, local circuit reorganization through its ability to control synaptogenesis, axonal pathfinding and myelination. Although activity-dependent activation of MMP-9 at specific synapses plays an important role in multiple plasticity mechanisms throughout the CNS, misregulated activation of the enzyme is implicated in a number of neurodegenerative disorders, including traumatic brain injury, multiple sclerosis, and Alzheimer’s disease. Growing evidence also suggests a role for MMP-9 in the pathophysiology of neurodevelopmental disorders including Fragile X Syndrome. This review outlines the various actions of MMP-9 during postnatal brain development, critical for future studies exploring novel therapeutic strategies for neurodevelopmental disorders. PMID:26283917

  20. Gluten Intolerance and Neurodevelopmental Disorders: Is Nitric Oxide the Common Biomarker Linking These Conditions?

    PubMed

    Fluegge, Keith

    2016-01-01

    Cruchet et al. attempt to tease out the myths and facts surrounding the growing popularity of certain dietary approaches in the management of neurodevelopmental disorders, like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). The authors identify a particular exclusionary-type approach that seeks to eliminate dietary gluten. Although the relationship between celiac disease (CD) and ADHD/ASD is not well established, a repeated clinical feature noted in CD is the elevated levels of nitric oxide in serum and urine. Elevated oxidative stress has also been observed in neurodevelopmental conditions, and the author of this correspondence has been the first to propose that chronic, environmental exposure to the air pollutant, nitrous oxide may contribute to these oxidative stress profiles through neural cholinergic perturbation. Therefore, the purpose of this correspondence is to highlight this biochemical connection between these conditions so as to identify the clinical populations who may realize the greatest benefit of these dietary approaches, while minimizing any potential risk of nutrient deficiencies. PMID:27498299

  1. Comparison of Grammar in Neurodevelopmental Disorders: The Case of Binding in Williams Syndrome and Autism with and without Language Impairment

    ERIC Educational Resources Information Center

    Perovic, Alexandra; Modyanova, Nadya; Wexler, Ken

    2013-01-01

    This study investigates whether distinct neurodevelopmental disorders show distinct patterns of impairments in particular grammatical abilities and the relation of those grammatical patterns to general language delays and intellectual disabilities. We studied two disorders (autism and Williams syndrome [WS]) and two distinct properties (Principle…

  2. Participation of underrepresented minority children in clinical trials for Fragile X syndrome and other neurodevelopmental disorders

    PubMed Central

    Chechi, Tasleem; Siyahian, Salpi; Thairu, Lucy; Hagerman, Randi; Lozano, Reymundo

    2014-01-01

    Summary The purpose of this study was to identify demographic data, motivational factors and barriers for participation in clinical trials (CTs) at the University of California Davis, MIND Institute. We conducted a cross-sectional survey in 100 participants (81 females and 19 males). The participants had high education levels (only 2% had not completed high school), a mean age of 44 years (SD ± 9.899) and had at least one child with a neurodevelopmental disorder. The diagnosis of Fragile X syndrome (FXS) had a significant association with past participation in CTs (p < 0.001). A statistical significance for age of diagnosis and participation in CTs was also found (z = −2.01, p = 0.045). The motivating factors were to help find cures/treatments for neurodevelopmental disorders and to relieve symptoms related to child's diagnosis. Factors explaining lack of participation, unwillingness to participate or unsure of participation were: lack of information/knowledge about the trials, time commitment to participation (screening, appointments, assessments, laboratory tests, etc.) and low annual household income. These results show that a portion of underrepresented minorities (URM) not participating in CTs are willing to participate and suggests that reducing barriers, particularly lack of knowledge/information and time commitment to trials are needed to improve recruitment. PMID:25606364

  3. Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

    PubMed

    Chauhan, Ved; Chauhan, Abha

    2016-06-01

    Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders. PMID:27151262

  4. Visual phenotype in Williams-Beuren syndrome challenges magnocellular theories explaining human neurodevelopmental visual cortical disorders

    PubMed Central

    Castelo-Branco, Miguel; Mendes, Mafalda; Sebastião, Ana Raquel; Reis, Aldina; Soares, Mário; Saraiva, Jorge; Bernardes, Rui; Flores, Raquel; Pérez-Jurado, Luis; Silva, Eduardo

    2007-01-01

    Williams-Beuren syndrome (WBS), a neurodevelopmental genetic disorder whose manifestations include visuospatial impairment, provides a unique model to link genetically determined loss of neural cell populations at different levels of the nervous system with neural circuits and visual behavior. Given that several of the genes deleted in WBS are also involved in eye development and the differentiation of retinal layers, we examined the retinal phenotype in WBS patients and its functional relation to global motion perception. We discovered a low-level visual phenotype characterized by decreased retinal thickness, abnormal optic disk concavity, and impaired visual responses in WBS patients compared with age-matched controls by using electrophysiology, confocal and coherence in vivo imaging with cellular resolution, and psychophysics. These mechanisms of impairment are related to the magnocellular pathway, which is involved in the detection of temporal changes in the visual scene. Low-level magnocellular performance did not predict high-level deficits in the integration of motion and 3D information at higher levels, thereby demonstrating independent mechanisms of dysfunction in WBS that will require remediation strategies different from those used in other visuospatial disorders. These findings challenge neurodevelopmental theories that explain cortical deficits based on low-level magnocellular impairment, such as regarding dyslexia. PMID:18037993

  5. Ultrasonic vocalizations: a tool for behavioural phenotyping of mouse models of neurodevelopmental disorders

    PubMed Central

    Scattoni, Maria Luisa; Crawley, Jacqueline; Ricceri, Laura

    2009-01-01

    In neonatal mice ultrasonic vocalizations have been studied both as an early communicative behavior of the pup-mother dyad and as a sign of an aversive affective state. Adult mice of both sexes produce complex ultrasonic vocalization patterns in different experimental/social contexts. All these vocalizations are becoming an increasingly valuable assay for behavioral phenotyping throughout the mouse life-span and alterations of the ultrasound patterns have been reported in several mouse models of neurodevelopmental disorders. Here we also show that the modulation of vocalizations by maternal cues (maternal potentiation paradigm) – originally identified and investigated in rats - can be measured in C57Bl/6 mouse pups with appropriate modifications of the rat protocol and can likely be applied to mouse behavioral phenotyping. In addition we suggest that a detailed qualitative evaluation of neonatal calls together with analysis of adult mouse vocalization patterns in both sexes in social settings, may lead to a greater understanding of the communication value of vocalizations in mice. Importantly, both neonatal and adult USV altered patterns can be determined during the behavioural phenotyping of mouse models of human neurodevelopmental and neuropsychiatric disorders, starting from those in which deficits in communication are a primary symptom. PMID:18771687

  6. Comorbidity of Physical and Mental Disorders in the Neurodevelopmental Genomics Cohort Study

    PubMed Central

    Calkins, Monica E.; Burstein, Marcy; He, Jian-Ping; Chiavacci, Rosetta; Lateef, Tarannum; Ruparel, Kosha; Gur, Ruben C.; Lehner, Thomas; Hakonarson, Hakon; Gur, Raquel E.

    2015-01-01

    OBJECTIVES: To examine patterns of associations between a broad range of mental and physical conditions by using a large, systematically obtained pediatric registry. METHODS: The sample included 9014 youth ages 8 to 21 years (4349 males and 4665 females; 3585 aged <13 years, 3678 aged 13 to 18 years, and 1751 aged 19 to 21 years) from the Philadelphia Neurodevelopmental Cohort identified through pediatric clinics at the Children’s Hospital of Philadelphia health care network by the Center for Applied Genomics. Measures were as follows: physical condition based on electronic medical records and interview data on 42 physical conditions of 14 organ systems/specialties and mental disorders based on an abbreviated version of the structured Kiddie-Schedule for Affective Disorders and Schizophrenia psychiatric diagnostic interview. RESULTS: There was a direct association between the severity of the physical condition and most classes of mental disorders, as well as with functional impairment. Models adjusted for sociodemographic correlates, other physical and mental disorders, and false discovery and revealed broad patterns of associations between neurodevelopmental disorders with behavior disorders (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.3–1.8; P < .004) and attention-deficit/hyperactivity disorder (OR: 3.1; 95% CI: 2.7–3.6; P < .0001), and neurologic/central nervous system conditions (OR: 1.3; 95% CI: 1.1–1.9; P < .05) with mood disorders and attention-deficit/hyperactivity disorder (OR: 1.3; 95% CI: 1.1–1.5; P < .001), and autoimmune/inflammatory conditions with mood disorders (OR: 1.4; 95% CI: 1.1–1.8, P < .05). CONCLUSIONS: Findings show the strong overlap between physical and mental conditions and their impact on severity and functional impairment in youth. Specific patterns of comorbidity have important implications for etiology. Prospective tracking of cross-disorder morbidity will be important to establish more effective mechanisms for

  7. Neurodevelopmental Plasticity in Pre- and Postnatal Environmental Interactions: Implications for Psychiatric Disorders from an Evolutionary Perspective

    PubMed Central

    Lee, Young-A; Yamaguchi, Yoshie; Goto, Yukiori

    2015-01-01

    Psychiatric disorders are disadvantageous behavioral phenotypes in humans. Accordingly, a recent epidemiological study has reported decreased fecundity in patients with psychiatric disorders, such as schizophrenia and autism spectrum disorders. Moreover, the fecundity of the relatives of these patients is not exceedingly higher compared to the fecundity of the relatives of normal subjects. Collectively, the prevalence of psychiatric disorders among humans is expected to decrease over generations. Nevertheless, in reality, the prevalence rates of psychiatric disorders in humans either have been constant over a long period of time or have even increased more recently. Several attempts to explain this fact have been made using biological mechanisms, such as de novo gene mutations or variants, although none of these explanations is fully comprehensive. Here, we propose a hypothesis towards understanding the biological mechanisms of psychiatric disorders from evolutionary perspectives. This hypothesis considers that behavioral phenotypes associated with psychiatric disorders might have emerged in the evolution of organisms as a neurodevelopmental adaptation against adverse environmental conditions associated with stress. PMID:26060583

  8. Epigenetic Regulation of UBE3A and Roles in Human Neurodevelopmental Disorders

    PubMed Central

    LaSalle, Janine M.; Reiter, Lawrence T.; Chamberlain, Stormy J.

    2016-01-01

    Summary The E3 ubiquitin ligase protein UBE3A, also known as E6-AP, has a multitude of ascribed functions and targets relevant to human health and disease. Epigenetic regulation of the UBE3A gene by parentally imprinted noncoding transcription within human chromosome 15q11.2-q13.3 is responsible for the maternal-specific effects of 15q11.2-q13.3 deletion or duplication disorders. Here, we review the evidence for diverse and emerging roles for UBE3A in the proteasome, synapse, and nucleus in regulating protein stability and transcription as well as the current mechanistic understanding of UBE3A imprinting in neurons. Angelman and Dup15q syndromes as well as experimental models of these neurodevelopmental disorders are highlighted as improving understanding of UBE3A and its complex regulation for improving therapeutic strategies. PMID:26585570

  9. Genetic and environmental modulation of neurodevelopmental disorders: Translational insights from labs to beds.

    PubMed

    Homberg, Judith R; Kyzar, Evan J; Scattoni, Maria Luisa; Norton, William H; Pittman, Julian; Gaikwad, Siddharth; Nguyen, Michael; Poudel, Manoj K; Ullmann, Jeremy F P; Diamond, David M; Kaluyeva, Aleksandra A; Parker, Matthew O; Brown, Richard E; Song, Cai; Gainetdinov, Raul R; Gottesman, Irving I; Kalueff, Allan V

    2016-07-01

    Neurodevelopmental disorders (NDDs) are a heterogeneous group of prevalent neuropsychiatric illnesses with various degrees of social, cognitive, motor, language and affective deficits. NDDs are caused by aberrant brain development due to genetic and environmental perturbations. Common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Genetic and epigenetic/environmental factors play a key role in these NDDs with significant societal impact. Given the lack of their efficient therapies, it is important to gain further translational insights into the pathobiology of NDDs. To address these challenges, the International Stress and Behavior Society (ISBS) has established the Strategic Task Force on NDDs. Summarizing the Panel's findings, here we discuss the neurobiological mechanisms of selected common NDDs and a wider NDD+ spectrum of associated neuropsychiatric disorders with developmental trajectories. We also outline the utility of existing preclinical (animal) models for building translational and cross-diagnostic bridges to improve our understanding of various NDDs. PMID:27113433

  10. Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review.

    PubMed

    Saeedi Saravi, Seyed Soheil; Dehpour, Ahmad Reza

    2016-01-15

    Organochlorine pesticides (OCPs) are persistent and bioaccumulative environmental contaminants with potential neurotoxic effects. The growing body of evidence has demonstrated that prenatal exposure to organochlorines (OCs) is associated with impairment of neuropsychological development. The hypothesis is consistent with recent studies emphasizing the correlation of environmental as well as genetic factors to the pathophysiology of neurodevelopmental and neurobehavioral defects. It has been suggested that maternal exposure to OCPs results in impaired motor and cognitive development in newborns and infants. Moreover, in utero exposure to these compounds contributes to the etiology of autism. Although impaired neurodevelopment occurs through prenatal exposure to OCs, breastfeeding causes postnatal toxicity in the infants. Parkinson's disease (PD) is another neurological disorder, which has been associated with exposure to OCs, leading to α-synuclein accumulation and depletion of dopaminergic neurons. The study aimed to review the potential association between pre- and post-natal exposure to OCs and impaired neurodevelopmental processes during pregnancy and neuropsychological diseases such as PD, behavioral alterations, seizures and autism. PMID:26549647

  11. Mitochondrial Biogenesis: A Therapeutic Target for Neurodevelopmental Disorders and Neurodegenerative Diseases

    PubMed Central

    Uittenbogaard, Martine; Chiaramello, Anne

    2014-01-01

    In the developing and mature brain, mitochondria act as central hubs for distinct but interwined pathways, necessary for neural development, survival, activity, connectivity and plasticity. In neurons, mitochondria assume diverse functions, such as energy production in the form of ATP, calcium buffering and generation of reactive oxygen species. Mitochondrial dysfunction contributes to a range of neurodevelopmental and neurodegenerative diseases, making mitochondria a potential target for pharmacological-based therapies. Pathogenesis associated with these diseases is accompanied by an increase in mitochondrial mass, a quantitative increase to overcome a qualitative deficiency due to mutated mitochondrial proteins that are either nuclear- or mitochondrial-encoded. This compensatory biological response is maladaptive, as it fails to sufficiently augment the bioenergetically functional mitochondrial mass and correct for the ATP deficit. Since regulation of neuronal mitochondrial biogenesis has been scantily investigated, our current understanding on the network of transcriptional regulators, co-activators and signaling regulators mainly derives from other cellular systems. The purpose of this review is to present the current state of our knowledge and understanding of the transcriptional and signaling cascades controlling neuronal mitochondrial biogenesis and the various therapeutic approaches to enhance the functional mitochondrial mass in the context of neurodevelopmental disorders and adult-onset neurodegenerative diseases. PMID:24606804

  12. Srgap3⁻/⁻ mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes.

    PubMed

    Waltereit, Robert; Leimer, Uwe; von Bohlen Und Halbach, Oliver; Panke, Jutta; Hölter, Sabine M; Garrett, Lillian; Wittig, Karola; Schneider, Miriam; Schmitt, Camie; Calzada-Wack, Julia; Neff, Frauke; Becker, Lore; Prehn, Cornelia; Kutscherjawy, Sergej; Endris, Volker; Bacon, Claire; Fuchs, Helmut; Gailus-Durner, Valérie; Berger, Stefan; Schönig, Kai; Adamski, Jerzy; Klopstock, Thomas; Esposito, Irene; Wurst, Wolfgang; de Angelis, Martin Hrabe; Rappold, Gudrun; Wieland, Thomas; Bartsch, Dusan

    2012-11-01

    Mutations in the SRGAP3 gene residing on chromosome 3p25 have previously been associated with intellectual disability. Genome-wide association studies have also revealed SRGAP3, together with genes from the same cellular network, as risk genes for schizophrenia. SRGAP3 regulates cytoskeletal dynamics through the RHO protein RAC1. RHO proteins are known to be involved in cytoskeletal reorganization during brain development to control processes such as synaptic plasticity. To elucidate the importance of SRGAP3 in brain development, we generated Srgap3-knockout mice. Ten percent of these mice developed a hydrocephalus and died before adulthood. Surviving mice showed various neuroanatomical changes, including enlarged lateral ventricles, white matter tracts, and dendritic spines together with molecular changes, including an increased basal activity of RAC1. Srgap3(-/-) mice additionally exhibited a complex behavioral phenotype. Behavioral studies revealed an impaired spontaneous alternation and social behavior, while long-term memory was unchanged. The animals also had tics. Lower locomotor activity was observed in male Srgap3(-/-) only. Srgap3(-/-) mice showed increased methylphenidate stimulation in males and an impaired prepulse inhibition in females. Together, the results show neurodevelopmental aberration in Srgap3(-/-) mice, with many of the observed phenotypes matching several schizophrenia-related intermediate phenotypes. Mutations of SRGAP3 may thus contribute to various neurodevelopmental disorders. PMID:22820399

  13. Neurodevelopmental variability in three young girls with a rare chromosomal disorder, 48, XXXX.

    PubMed

    Samango-Sprouse, Carole; Keen, Colleen; Mitchell, Francie; Sadeghin, Teresa; Gropman, Andrea

    2015-10-01

    Fourty eight, XXXX is a rare chromosomal aneuploidy associated with neurocognitive deficits, speech and language disorders and executive dysfunction but the scarcity and variability of reported cases limit our understanding of the 48, XXXX phenotype. To our knowledge, this is the first study to report on the neurodevelopmental profile of three young females with 48, XXXX. Patient 1 (age = 11.0), Patient 2 (age = 10.9), and Patient 3 (age = 6.4) were evaluated using comprehensive neurodevelopmental assessments. Parent questionnaires were completed to assess behavioral and psychosocial domains including executive function, ADHD and anxiety. Nonverbal intelligence quotients were 56, 80, and 91 for Patients 1, 2, and 3, respectively. There were significantly impaired visual motor capacities in graphomotor and perceptual domains below the 5th centile in Patients 1 and 2, and mildly impaired visual perception skills in Patient 3. All three patients had Childhood Apraxia of Speech (CAS) but of varying severity and similar executive dysfunction, externalizing problems and social difficulties. Familial learning disabilities (FLD) in Patient 1 and the co-occurrence of ADHD in Patient's 1 and 2 may contribute to their more impaired cognitive performances relative to Patient 3 who is the second reported case of 48, XXXX to have normal intellect. These distinct and overlapping characteristics expand the phenotypic profile of 48, XXXX and may be used in the counseling of families and treatment of children with 48, XXXX. PMID:26086740

  14. Alcohol-Related Liver Disease

    MedlinePlus

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  15. Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders

    PubMed Central

    Levman, Jacob; Takahashi, Emi

    2015-01-01

    Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us. PMID:26640765

  16. Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders.

    PubMed

    Levman, Jacob; Takahashi, Emi

    2015-01-01

    Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us. PMID:26640765

  17. Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

    PubMed Central

    Picchioni, Dante; Reith, R. Michelle; Nadel, Jeffrey L.; Smith, Carolyn B.

    2014-01-01

    Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders. PMID:24839550

  18. Proliferation and Differentiation Deficits are a Major Convergence Point for Neurodevelopmental Disorders.

    PubMed

    Ernst, Carl

    2016-05-01

    Several lines of evidence suggest that proliferation and differentiation in neural stem cells (NSCs) are a major convergence point of neurodevelopmental disorders (NDDs). Most genes with truncating mutations are implicated in NSC proliferation and differentiation (e.g., MBD5, CDKL5, and MECP2). Similarly, reciprocal deletion/duplication copy-number variants (CNVs), such as 1q21.1 and 16p11.2, are inversely correlated with head size. In addition, pathways such as MAPK, mTOR, and RAS, which are important in cancer, a disease of uncontrolled cell proliferation, are implicated in NDDs. These deficits are a measurable output of patient-derived induced neural progenitor cells, and may represent a diagnostic tool and a possible clinical intervention point for molecular therapies, irrespective of genotype. PMID:27032601

  19. Practitioner Review: Short-Term and Working Memory Impairments in Neurodevelopmental Disorders--Diagnosis and Remedial Support

    ERIC Educational Resources Information Center

    Gathercole, Susan E.; Alloway, Tracy Packiam

    2006-01-01

    Background: This article provides an introduction to current models of working and short-term memory, their links with learning, and diagnosis of impairments. The memory impairments associated with a range of neurodevelopmental disorders (Down's syndrome, Williams syndrome, Specific Language Impairment, and attentional deficits) are discussed.…

  20. The Effects of Live Music as the Discriminative Stimulus and Reinforcer on the Skill Acquisition of Learners with Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Harms, Melanie D.

    2013-01-01

    Individuals with neurodevelopmental disorders are challenged with memory and language deficits that impact their skills acquisition (Martin, Klusek, Estigarriba, & Roberts, 2009; Turner & Alborz, 2003). The value of music when applied as an antecedent and a reinforcer has long been established to address such memory and language deficits…

  1. Genetic Controls Balancing Excitatory and Inhibitory Synaptogenesis in Neurodevelopmental Disorder Models

    PubMed Central

    Gatto, Cheryl L.; Broadie, Kendal

    2010-01-01

    Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis. The affected genes often encode synaptic components directly, but also include regulators that secondarily mediate the synthesis or assembly of synaptic proteins. The prime example is Fragile X syndrome (FXS), the leading heritable cause of both intellectual disability and autism spectrum disorders. FXS results from loss of mRNA-binding FMRP, which regulates synaptic transcript trafficking, stability and translation in activity-dependent synaptogenesis and plasticity mechanisms. Genetic models of FXS exhibit striking excitatory and inhibitory synapse imbalance, associated with impaired cognitive and social interaction behaviors. Downstream of translation control, a number of specific synaptic proteins regulate excitatory versus inhibitory synaptogenesis, independently or combinatorially, and loss of these proteins is also linked to disrupted neurodevelopment. The current effort is to define the cascade of events linking transcription, translation and the role of specific synaptic proteins in the maintenance of excitatory versus inhibitory synapses during neural circuit formation. This focus includes mechanisms that fine-tune excitation and inhibition during the refinement of functional synaptic circuits, and later modulate this balance throughout life. The use of powerful new genetic models has begun to shed light on the mechanistic bases of excitation/inhibition imbalance for a range of neurodevelopmental disease states. PMID:21423490

  2. In Pursuit of New Imprinting Syndromes by Epimutation Screening in Idiopathic Neurodevelopmental Disorder Patients.

    PubMed

    Mayo, Sonia; Monfort, Sandra; Roselló, Mónica; Oltra, Silvestre; Orellana, Carmen; Martínez, Francisco

    2015-01-01

    Alterations of epigenetic mechanisms, and more specifically imprinting modifications, could be responsible of neurodevelopmental disorders such as intellectual disability (ID) or autism together with other associated clinical features in many cases. Currently only eight imprinting syndromes are defined in spite of the fact that more than 200 genes are known or predicted to be imprinted. Recent publications point out that some epimutations which cause imprinting disorders may affect simultaneously different imprinted loci, suggesting that DNA-methylation may have been altered more globally. Therefore, we hypothesised that the detection of altered methylation patterns in known imprinting loci will indirectly allow identifying new syndromes due to epimutations among patients with unexplained ID. In a screening for imprinting alterations in 412 patients with syndromic ID/autism we found five patients with altered methylation in the four genes studied: MEG3, H19, KCNQ1OT1, and SNRPN. Remarkably, the cases with partial loss of methylation in KCNQ1OT1 and SNRPN present clinical features different to those associated with the corresponding imprinting syndromes, suggesting a multilocus methylation defect in accordance with our initial hypothesis. Consequently, our results are a proof of concept that the identification of epimutations in known loci in patients with clinical features different from those associated with known syndromes will eventually lead to the definition of new imprinting disorders. PMID:26106604

  3. In Pursuit of New Imprinting Syndromes by Epimutation Screening in Idiopathic Neurodevelopmental Disorder Patients

    PubMed Central

    Mayo, Sonia; Monfort, Sandra; Roselló, Mónica; Oltra, Silvestre; Orellana, Carmen; Martínez, Francisco

    2015-01-01

    Alterations of epigenetic mechanisms, and more specifically imprinting modifications, could be responsible of neurodevelopmental disorders such as intellectual disability (ID) or autism together with other associated clinical features in many cases. Currently only eight imprinting syndromes are defined in spite of the fact that more than 200 genes are known or predicted to be imprinted. Recent publications point out that some epimutations which cause imprinting disorders may affect simultaneously different imprinted loci, suggesting that DNA-methylation may have been altered more globally. Therefore, we hypothesised that the detection of altered methylation patterns in known imprinting loci will indirectly allow identifying new syndromes due to epimutations among patients with unexplained ID. In a screening for imprinting alterations in 412 patients with syndromic ID/autism we found five patients with altered methylation in the four genes studied: MEG3, H19, KCNQ1OT1, and SNRPN. Remarkably, the cases with partial loss of methylation in KCNQ1OT1 and SNRPN present clinical features different to those associated with the corresponding imprinting syndromes, suggesting a multilocus methylation defect in accordance with our initial hypothesis. Consequently, our results are a proof of concept that the identification of epimutations in known loci in patients with clinical features different from those associated with known syndromes will eventually lead to the definition of new imprinting disorders. PMID:26106604

  4. Gene expression in maturing neurons: regulatory mechanisms and related neurodevelopmental disorders.

    PubMed

    Ding, Baojin

    2015-04-25

    During the central nervous system (CNS) development, the interactions between intrinsic genes and extrinsic environment ensure that each neuronal developmental stage (eg. neuronal proliferation, differentiation, migration, axon extension, dendritogenesis and formation of functional synapses) occurs in the proper timing and sequence. The successful coordination requires that numerous groups of genes are exquisitely regulated in a spatiotemporal manner by various regulatory mechanisms, including sequence-specific DNA-binding proteins, histone modifications, DNA methylation, chromatin remodeling, and microRNAs (miRNAs). By targeting chromatin structure, transcription and translation processes, these mechanisms form a regulatory network to accomplish the fine regulation of gene expression in response to environmental stimuli at different developmental stages. Dysregulation of the gene expression during neuronal development has been shown to be implicated in a number of neurodevelopmental disorders, such as autism spectrum disorders (ASD), Rett syndrome (RTT), Fragile-X syndrome (FXS) and other genetic diseases. The further understanding of the regulation of gene expression during neuronal development may provide new approaches for the diagnosis and treatment of these disorders. PMID:25896042

  5. Assessing the Influence of Researcher-Partner Involvement on the Process and Outcomes of Participatory Research in Autism Spectrum Disorder and Neurodevelopmental Disorders: A Scoping Review

    ERIC Educational Resources Information Center

    Jivraj, Jamil; Sacrey, Lori-Ann; Newton, Amanda; Nicholas, David; Zwaigenbaum, Lonnie

    2014-01-01

    Participatory research aims to increase the relevance and broaden the implementation of health research by involving those affected by the outcomes of health studies. Few studies within the field of neurodevelopmental disorders, particularly autism spectrum disorders, have involved autistic individuals as partners. This study sought to identify…

  6. Assessing the influence of researcher-partner involvement on the process and outcomes of participatory research in autism spectrum disorder and neurodevelopmental disorders: a scoping review.

    PubMed

    Jivraj, Jamil; Sacrey, Lori-Ann; Newton, Amanda; Nicholas, David; Zwaigenbaum, Lonnie

    2014-10-01

    Participatory research aims to increase the relevance and broaden the implementation of health research by involving those affected by the outcomes of health studies. Few studies within the field of neurodevelopmental disorders, particularly autism spectrum disorders, have involved autistic individuals as partners. This study sought to identify and characterize published participatory research partnerships between researchers and individuals with autism spectrum disorder or other neurodevelopmental disorders and examine the influence of participatory research partnerships on the research process and reported study outcomes. A search of databases and review of gray literature identified seven studies that described participatory research partnerships between academic researchers and individuals with autism spectrum disorder or other neurodevelopmental disorders. A comparative analysis of the studies revealed two key themes: (1) variations in the participatory research design and (2) limitations during the reporting of the depth of the partner's involvement. Both themes potentially limit the application and generalizability of the findings. The results of the review are discussed in relation to the use of evaluative frameworks for such participatory research studies to determine the potential benefits of participatory research partnerships within the neurodevelopmental and autism spectrum disorder populations. PMID:24989447

  7. Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study

    PubMed Central

    Geraghty, Estella M.; Tancredi, Daniel J.; Delwiche, Lora D.; Schmidt, Rebecca J.; Ritz, Beate; Hansen, Robin L.; Hertz-Picciotto, Irva

    2014-01-01

    Background: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. Objectives: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Methods: The CHARGE study is a population-based case–control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997–2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316). Results: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified. Conclusions: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of

  8. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

    PubMed Central

    Kroon, Tim; Sierksma, Martijn C.; Meredith, Rhiannon M.

    2013-01-01

    Brain function and behavior undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability (ID) neurodevelopmental disorders (NDDs) and their corresponding genetic mouse models, impairments in many neuronal and behavioral phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioral development (referred to also as “neurotypical” development) and timing of NDD impairments are not fully investigated. This perspective highlights temporal patterns of synaptic and neuronal impairment, with a restricted focus on autism and ID types of NDDs. Given the varying known genetic and environmental causes for NDDs, this perspective proposes two strategies for investigation: (1) a focus on neurobiological mechanisms underlying known critical periods in the (typically) normal-developing brain; (2) investigation of spatio-temporal expression profiles of genes implicated in monogenic syndromes throughout affected brain regions. This approach may help explain why many NDDs with differing genetic causes can result in overlapping phenotypes at similar developmental stages and better predict vulnerable periods within these disorders, with implications for both therapeutic rescue and ultimately, prevention. PMID:24198768

  9. Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders

    PubMed Central

    Coiro, Pierluca; Padmashri, Ragunathan; Suresh, Anand; Spartz, Elizabeth; Pendyala, Gurudutt; Chou, Shinnyi; Jung, Yoosun; Meays, Brittney; Roy, Shreya; Gautam, Nagsen; Alnouti, Yazen; Li, Ming; Dunaevsky, Anna

    2016-01-01

    Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs. Significantly, spine impairments persisted into adulthood and correlated with increased repetitive behavior, an ASD relevant behavioral phenotype. Structural analysis of synaptic inputs revealed a reorganization of presynaptic inputs with a larger proportion of spines being contacted by both excitatory and inhibitory presynaptic terminals. These structural impairments were accompanied by altered excitatory and inhibitory synaptic transmission. Finally, we report that a postnatal treatment of MIA offspring with the anti-inflammatory drug ibudilast, prevented both synaptic and behavioral impairments. Our results suggest that a possible altered inflammatory state associated with maternal immune activation results in impaired synaptic development that persists into adulthood but which can be prevented with early anti-inflammatory treatment. PMID:26218293

  10. Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders

    PubMed Central

    2014-01-01

    Background Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. Methods To help unravel this genetic complexity, we performed whole exome sequencing on 100 ASD individuals from 40 families with multiple distantly related affected individuals. All families contained a minimum of one pair of ASD cousins. Each individual was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Burrows-Wheeler Aligner (BWA), Genome Analysis Toolkit (GATK), and SeattleSeq. Genotyping information on each family was utilized in order to determine genomic regions that were identical by descent (IBD). Variants identified by exome sequencing which occurred in IBD regions and present in all affected individuals within each family were then evaluated to determine which may potentially be disease related. Nucleotide alterations that were novel and rare (minor allele frequency, MAF, less than 0.05) and predicted to be detrimental, either by altering amino acids or splicing patterns, were prioritized. Results We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1), schizophrenia (WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the

  11. Learning Curve Analyses in Neurodevelopmental Disorders: Are Children with Autism Spectrum Disorder Truly Visual Learners?

    ERIC Educational Resources Information Center

    Erdodi, Laszlo; Lajiness-O'Neill, Renee; Schmitt, Thomas A.

    2013-01-01

    Visual and auditory verbal learning using a selective reminding format was studied in a mixed clinical sample of children with autism spectrum disorder (ASD) (n = 42), attention-deficit hyperactivity disorder (n = 83), velocardiofacial syndrome (n = 17) and neurotypicals (n = 38) using the Test of Memory and Learning to (1) more thoroughly…

  12. Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

    PubMed Central

    Wise, Merrill S.

    2016-01-01

    Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population. PMID:27478646

  13. Emphasizing the health benefits of vitamin D for those with neurodevelopmental disorders and intellectual disabilities.

    PubMed

    Grant, William B; Wimalawansa, Sunil J; Holick, Michael F; Cannell, John J; Pludowski, Pawel; Lappe, Joan M; Pittaway, Mary; May, Philip

    2015-03-01

    People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies. PMID:25734565

  14. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders

    PubMed Central

    Soden, Sarah E.; Saunders, Carol J.; Willig, Laurel K.; Farrow, Emily G.; Smith, Laurie D.; Petrikin, Josh E.; LePichon, Jean-Baptiste; Miller, Neil A.; Thiffault, Isabelle; Dinwiddie, Darrell L.; Twist, Greyson; Noll, Aaron; Heese, Bryce A.; Zellmer, Lee; Atherton, Andrea M.; Abdelmoity, Ahmed T.; Safina, Nicole; Nyp, Sarah S.; Zuccarelli, Britton; Larson, Ingrid A.; Modrcin, Ann; Herd, Suzanne; Creed, Mitchell; Ye, Zhaohui; Yuan, Xuan; Brodsky, Robert A.; Kingsmore, Stephen F.

    2014-01-01

    Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients. PMID:25473036

  15. Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition.

    PubMed

    Gruber, Reut; Wise, Merrill S

    2016-01-01

    Empirical evidence indicates that sleep spindles facilitate neuroplasticity and "off-line" processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population. PMID:27478646

  16. Self-injurious behavior in neurodevelopmental disorders: relevance of nociceptive and immune mechanisms.

    PubMed

    Symons, Frank J

    2011-04-01

    Self-injurious behavior (SIB) among individuals with intellectual and related neurodevelopmental disorders (IDD) is a clinical challenge and scientific puzzle. The physiological mechanisms regulating the sensory components of SIB remain a mystery with no clear understanding of the underlying pathophysiology. The central dogma regarding sensory processing in general and pain in particular among individuals with IDD and chronic SIB is that sensory processing is reduced and pain is absent or blunted. In this paper, recent findings challenging some of the conventional wisdom regarding pain and sensory function among individuals with IDD and SIB are reviewed. It seems that at least a subgroup of individuals with IDD and chronic SIB may be in a physiological state similar to neuropathic pain in which hyperalgesia is mediated by plasticity mechanisms regulating inflammatory, immune, and nociceptive systems. In response to repeated tissue damage associated with chronic self-injury, innate immune cells may be producing pro-inflammatory and pro-nociceptive cytokines that act on the brain to cause sickness-like behavior and sensitize primary sensory nerve afferents contributing to pain hypersensitivity (i.e., hyperalgesia). PMID:21237197

  17. Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

    PubMed Central

    Lahiri, Debomoy K.; Sokol, Deborah K.; Erickson, Craig; Ray, Balmiki; Ho, Chang Y.; Maloney, Bryan

    2013-01-01

    Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secreted APP α, is elevated in persons with autism. This has led to the “anabolic hypothesis” of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein, Ras small GTPase/extracellular signal-regulated kinase, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin. We also present additional evidence of magnetic resonance imaging intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP’s involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP’s contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence. PMID:23801940

  18. Emphasizing the Health Benefits of Vitamin D for Those with Neurodevelopmental Disorders and Intellectual Disabilities

    PubMed Central

    Grant, William B.; Wimalawansa, Sunil J.; Holick, Michael F.; Cannell, John J.; Pludowski, Pawel; Lappe, Joan M.; Pittaway, Mary; May, Philip

    2015-01-01

    People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies. PMID:25734565

  19. The Role of Ionotropic Glutamate Receptors in Childhood Neurodevelopmental Disorders: Autism Spectrum Disorders and Fragile X Syndrome

    PubMed Central

    Uzunova, Genoveva; Hollander, Eric; Shepherd, Jason

    2014-01-01

    Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are relatively common childhood neurodevelopmental disorders with increasing incidence in recent years. They are currently accepted as disorders of the synapse with alterations in different forms of synaptic communication and neuronal network connectivity. The major excitatory neurotransmitter system in brain, the glutamatergic system, is implicated in learning and memory, synaptic plasticity, neuronal development. While much attention is attributed to the role of metabotropic glutamate receptors in ASD and FXS, studies indicate that the ionotropic glutamate receptors (iGluRs) and their regulatory proteins are also altered in several brain regions. Role of iGluRs in the neurobiology of ASD and FXS is supported by a weight of evidence that ranges from human genetics to in vitro cultured neurons. In this review we will discuss clinical, molecular, cellular and functional changes in NMDA, AMPA and kainate receptors and the synaptic proteins that regulate them in the context of ASD and FXS. We will also discuss the significance for the development of translational biomarkers and treatments for the core symptoms of ASD and FXS. PMID:24533017

  20. One-carbon metabolism in neurodevelopmental disorders: using broad-based nutraceutics to treat cognitive deficits in complex spectrum disorders.

    PubMed

    Schaevitz, Laura; Berger-Sweeney, Joanne; Ricceri, Laura

    2014-10-01

    Folate and choline, two nutrients involved in the one-carbon metabolic cycle, are intimately involved in regulating DNA integrity, synthesis, biogenic amine synthesis, and methylation. In this review, we discuss evidence that folate and choline play an important role in normal cognitive development, and that altered levels of these nutrients during periods of high neuronal proliferation and synaptogenesis can result in diminished cognitive function. We also discuss the use of these nutrients as therapeutic agents in a spectrum of developmental disorders in which intellectual disability is a prominent feature, such as in Fragile-X, Rett syndrome, Down syndrome, and Autism spectrum disorders. A survey of recent literature suggests that nutritional supplements have mild, but generally consistent, effects on improving cognition. Intervening with supplements earlier rather than later during development is more effective in improving cognitive outcomes. Given the mild improvements seen after treatments using nutrients alone, and the importance of the genetic profile of parents and offspring, we suggest that using nutraceutics early in development and in combination with other therapeutics are likely to have positive impacts on cognitive outcomes in a broad spectrum of complex neurodevelopmental disorders. PMID:24769289

  1. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    ERIC Educational Resources Information Center

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  2. The clinical significance of small copy number variants in neurodevelopmental disorders

    PubMed Central

    Asadollahi, Reza; Oneda, Beatrice; Joset, Pascal; Azzarello-Burri, Silvia; Bartholdi, Deborah; Steindl, Katharina; Vincent, Marie; Cobilanschi, Joana; Sticht, Heinrich; Baldinger, Rosa; Reissmann, Regina; Sudholt, Irene; Thiel, Christian T; Ekici, Arif B; Reis, André; Bijlsma, Emilia K; Andrieux, Joris; Dieux, Anne; FitzPatrick, David; Ritter, Susanne; Baumer, Alessandra; Latal, Beatrice; Plecko, Barbara; Jenni, Oskar G; Rauch, Anita

    2014-01-01

    Background Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context. Methods By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1–500 kb in a cohort of 714 patients with undiagnosed NDDs. Results We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.4%) were confirmed. 6 of 14 confirmed de novo, one of two homozygous and four heterozygous inherited CNVs affected the known microdeletion regions 17q21.31, 16p11.2 and 2p21 or OMIM morbid genes (CASK, CREBBP, PAFAH1B1, SATB2; AUTS2, NRXN3, GRM8). Two further de novo CNVs affecting single genes (MED13L, CTNND2) were instrumental in delineating novel recurrent conditions. For the first time, we here report exonic deletions of CTNND2 causing low normal IQ with learning difficulties with or without autism spectrum disorder. Additionally, we discovered a homozygous out-of-frame deletion of ACOT7 associated with features comparable to the published mouse model. In total, 24.1% of the confirmed small CNVs were categorised as pathogenic or likely pathogenic (median size 130 kb), 17.2% as likely benign, 3.4% represented incidental findings and 55.2% remained unclear. Conclusions These results verify the diagnostic relevance of genome-wide rare CNVs <500 kb, which were found pathogenic in ∼2% (14/714) of cases (1.1% de novo, 0.3% homozygous, 0.6% inherited) and highlight their inherent potential for discovery of new conditions. PMID:25106414

  3. A Higher Mutational Burden in Females Supports a “Female Protective Model” in Neurodevelopmental Disorders

    PubMed Central

    Jacquemont, Sébastien; Coe, Bradley P.; Hersch, Micha; Duyzend, Michael H.; Krumm, Niklas; Bergmann, Sven; Beckmann, Jacques S.; Rosenfeld, Jill A.; Eichler, Evan E.

    2014-01-01

    Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a “female protective model.” We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in females compared to males (odds ratio [OR] = 1.46, p = 8 × 10−10) in a cohort of 15,585 probands ascertained for NDs. In an independent autism spectrum disorder (ASD) cohort of 762 families, we found a 3-fold increase in deleterious autosomal CNVs (p = 7 × 10−4) and an excess of private deleterious single-nucleotide variants (SNVs) in female compared to male probands (OR = 1.34, p = 0.03). We also showed that the deleteriousness of autosomal SNVs was significantly higher in female probands (p = 0.0006). A similar bias was observed in parents of probands ascertained for NDs. Deleterious CNVs (>400 kb) were maternally inherited more often (up to 64%, p = 10−15) than small CNVs < 400 kb (OR = 1.45, p = 0.0003). In the ASD cohort, increased maternal transmission was also observed for deleterious CNVs and SNVs. Although ASD females showed higher mutational burden and lower cognition, the excess mutational burden remained, even after adjustment for those cognitive differences. These results strongly suggest that females have an increased etiological burden unlinked to rare deleterious variants on the X chromosome. Carefully phenotyped and genotyped cohorts will be required for identifying the symptoms, which show gender-specific liability to mutational burden. PMID:24581740

  4. Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum.

    PubMed

    Richardson, A J; Ross, M A

    2000-01-01

    There is increasing evidence that abnormalities of fatty acid and membrane phospholipid metabolism play a part in a wide range of neurodevelopmental and psychiatric disorders. This proposal is discussed here in relation to attention-deficit/hyperactivity disorder (ADHD), dyslexia, developmental coordination disorder (dyspraxia) and the autistic spectrum. These are among the most common neurodevelopmental disorders of childhood, with significant implications for society as well as for those directly affected. However, controversy still surrounds both the identification and management of these conditions, and while their aetiology is recognized as being complex and multifactorial, little progress has yet been made in elucidating predisposing factors at the biological level. An overview is provided here of the contents of this Special Issue, which contains a selection of reports from a unique multidisciplinary workshop involving both researchers and clinicians. Its purpose was to explore the possibility that ADHD, dyslexia, dyspraxia and autism fall within a phospholipid spectrum of disorders. This proposal could explain the high degree of co-morbidity between these conditions, their aggregation within families and relation to other psychiatric disorders, and a range of associated features that are already well known at a clinical level. The existing evidence for fatty acid abnormalities in these disorders is summarized, and new approaches are outlined that have the potential to improve both the identification and the management of these and related neurodevelopmental and psychiatric conditions. PMID:10970706

  5. Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?

    PubMed Central

    Rajkumar, Ravi Philip

    2014-01-01

    Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF), early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed. PMID:25548672

  6. A Dual Comparative Approach: Integrating Lines of Evidence from Human Evolutionary Neuroanatomy and Neurodevelopmental Disorders

    PubMed Central

    Hanson, Kari L.; Hrvoj-Mihic, Branka; Semendeferi, Katerina

    2014-01-01

    The evolution of the human brain has been marked by a nearly three-fold increase in size since our divergence from the last common ancestor shared with chimpanzees and bonobos. Despite increased interest in comparative neuroanatomy and phylogenetic methods, relatively little is known regarding the effects that this enlargement has had on its internal organization, and how certain areas of the brain have differentially expanded over evolutionary time. Analyses of the microstructure of several regions of the human cortex and subcortical structures have demonstrated subtle changes at the cellular and molecular level, suggesting that the human brain is more than simply a ‘scaled-up’ primate brain. Ongoing research in comparative neuroanatomy has much to offer our understanding of human brain evolution. Through analysis of the neuroanatomical phenotype at the level of reorganization in cytoarchitecture and cellular morphology, new data continue to highlight changes in cell density and organization associated with volumetric changes in discrete regions. An understanding of the functional significance of variation in neural circuitry can further be approached through studies of atypical human development. Many neurodevelopmental disorders cause disruption in systems associated with uniquely human features of cognition, including language and social cognition. Understanding the genetic and developmental mechanisms that underlie variation in the human cognitive phenotype can help to clarify the functional significance of interspecific variation. By uniting approaches from comparative neuroanatomy and neuropathology, insights can be gained that clarify trends in human evolution. Here, we explore these lines of evidence, and their significance for understanding functional variation between species, and within neuropathological variation in the human brain. PMID:25247986

  7. A Population-based Longitudinal Study of Childhood Neurodevelopmental Disorders, IQ and Subsequent Risk of Psychotic Experiences in Adolescence

    PubMed Central

    Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B

    2014-01-01

    Background Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (ND). Yet longitudinal studies of psychotic outcomes among individuals with ND are limited. We report a population-based prospective study of six common childhood ND, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. Methods PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six neurodevelopmental disorders (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaire at age 9 years. Linear regression calculated mean difference in cognitive scores between those with and without ND. The association between ND and PEs was expressed as odds ratio (OR); effects of cognitive deficits were examined. Potential confounders included age, gender, father’s social class, ethnicity and maternal education. Results Out of 8,220 children, 487 (5.9%) were reported to have ND at age 9 years. Children with, compared with those without ND performed worse on all cognitive measures; adjusted mean difference in total IQ 6.84 (95% CI 5.00- 8.69). The association between total IQ and ND was linear (p<0.0001). The risk of PEs was higher in those with, compared with those without ND; adjusted OR for definite PEs 1.76 (95% CI 1.11- 2.79). IQ (but not working memory) deficit partly explained this association. Conclusion Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia. PMID:25066026

  8. What is schizophrenia: A neurodevelopmental or neurodegenerative disorder or a combination of both? A critical analysis

    PubMed Central

    Gupta, Swapnil; Kulhara, Parmanand

    2010-01-01

    The etiology of schizophrenia has been the focus of intensive research for a long time. Perspectives have changed drastically with the development of new investigative techniques. Clinical observations made by Kraepelin, Clouston, Bender, and Watt are now being complemented by neuroimaging and genetic studies to prove the neurodevelopmental hypothesis. At the same time, neuropathological and longitudinal studies of schizophrenia often support a neurodegenerative hypothesis. To provide a theoretical basis to the available evidence, another hypothesis called the progressive neurodevelopmental model has also emerged. This review presents some key evidence supporting each of these theories followed by a critical analysis of each. PMID:20174514

  9. Human alcohol-related neuropathology

    PubMed Central

    Kril, Jillian J.

    2015-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  10. Human alcohol-related neuropathology.

    PubMed

    de la Monte, Suzanne M; Kril, Jillian J

    2014-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  11. [Alcohol-related dementia].

    PubMed

    Matsui, Toshifumi; Yokoyama, Akira; Matsushita, Sachio; Kozaki, Koichi; Higuchi, Susumu

    2014-04-01

    Excessive alcohol use is associated with health problems for the elderly in combination with their chronic conditions. One such complication, alcohol-related dementia (ARD) is brought about by direct or indirect ethanol intoxication, and coexisting nutritional deficiency, liver disease, cerebrovascular disease and traumatic brain injury. The elderly people with ARD have been underestimated and underdiagnosed. In these older alcoholics, atrophic changes, lacunar infarcts and deep white matter lesions of the brain are evident and are associated not only with their cognitive decline, but also with their frailty, leading to high morbidity and mortality ratio. Although lifelong abstinence can recover patients with ARD to temporally lull, aging, the severity of alcohol dependence, and the concomitant nutritional, physical and environmental factors can all impact negatively their outcome. Therefore, a comprehensive approach to lifestyle factors is recommended so that they can minimize preventable risks and maintain health status. Nursing home placement may be an appropriate treatment option for some refractory, long-term patients with ARD. PMID:24796110

  12. Recurrent copy number variations as risk factors for neurodevelopmental disorders: critical overview and analysis of clinical implications.

    PubMed

    Torres, Fátima; Barbosa, Mafalda; Maciel, Patrícia

    2016-02-01

    Neurodevelopmental disorders (NDs) encompass a spectrum of neuropsychiatric manifestations. Chromosomal regions 1q21.1, 3q29, 15q11.2, 15q13.3, 16p11.2, 16p13.1 and 22q11 harbour rare but recurrent CNVs that have been uncovered as being important risk factors for several of these disorders. These rearrangements may underlie a broad phenotypical spectrum, ranging from normal development, to learning problems, intellectual disability (ID), epilepsy and psychiatric diseases, such as autism spectrum disorders (ASDs) and schizophrenia (SZ). The highly increased risk of developing neurodevelopmental phenotypes associated with some of these CNVs makes them an unavoidable element in the clinical context in paediatrics, neurology and psychiatry. However, and although finding these risk loci has been the goal of neuropsychiatric genetics for many years, the translation of this recent knowledge into clinical practice has not been trivial. In this article, we will: (1) review the state of the art on recurrent CNVs associated with NDs, namely ASD, ID, epilepsy and SZ; (2) discuss the models used to dissect the underlying neurobiology of disease, (3) discuss how this knowledge can be used in clinical practice. PMID:26502893

  13. Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females.

    PubMed

    Bain, Jennifer M; Cho, Megan T; Telegrafi, Aida; Wilson, Ashley; Brooks, Susan; Botti, Christina; Gowans, Gordon; Autullo, Leigh Anne; Krishnamurthy, Vidya; Willing, Marcia C; Toler, Tomi L; Ben-Zev, Bruria; Elpeleg, Orly; Shen, Yufeng; Retterer, Kyle; Monaghan, Kristin G; Chung, Wendy K

    2016-09-01

    Via whole-exome sequencing, we identified six females from independent families with a common neurodevelopmental phenotype including developmental delay, intellectual disability, autism, hypotonia, and seizures, all with de novo predicted deleterious variants in the nuclear localization signal of Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2, a gene located on the X chromosome. Many of the females also have seizures, psychiatric co-morbidities, and orthopedic, gastrointestinal, and growth problems as well as common dysmorphic facial features. HNRNPs are a large group of ubiquitous proteins that associate with pre-mRNAs in eukaryotic cells to produce a multitude of alternatively spliced mRNA products during development and play an important role in controlling gene expression. The failure to identify affected males, the severity of the neurodevelopmental phenotype in females, and the essential role of this gene suggests that male conceptuses with these variants may not be viable. PMID:27545675

  14. The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders

    PubMed Central

    Marques, Andrea Horvath; O'Connor, Thomas G.; Roth, Christine; Susser, Ezra; Bjørke-Monsen, Anne-Lise

    2013-01-01

    The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of maternal prenatal and infant nutritional status (from conception until early childhood) as well as maternal prenatal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early interventions. PMID:23914151

  15. Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders

    PubMed Central

    Barnes, SA; Pinto-Duarte, A; Kappe, A; Zembrzycki, A; Metzler, A; Mukamel, EA; Lucero, J; Wang, X; Sejnowski, TJ; Markou, A; Behrens, MM

    2015-01-01

    Alterations in glutamatergic transmission onto developing GABAergic systems, in particular onto parvalbumin-positive (Pv+) fast-spiking interneurons, have been proposed as underlying causes of several neurodevelopmental disorders, including schizophrenia and autism. Excitatory glutamatergic transmission, through ionotropic and metabotropic glutamate receptors, is necessary for the correct postnatal development of the Pv+ GABAergic network. We generated mutant mice in which the metabotropic glutamate receptor 5 (mGluR5) was specifically ablated from Pv+ interneurons postnatally, and investigated the consequences of such a manipulation at the cellular, network and systems levels. Deletion of mGluR5 from Pv+ interneurons resulted in reduced numbers of Pv+ neurons and decreased inhibitory currents, as well as alterations in event-related potentials and brain oscillatory activity. These cellular and sensory changes translated into domain-specific memory deficits and increased compulsive-like behaviors, abnormal sensorimotor gating and altered responsiveness to stimulant agents. Our findings suggest a fundamental role for mGluR5 in the development of Pv+ neurons and show that alterations in this system can produce broad-spectrum alterations in brain network activity and behavior that are relevant to neurodevelopmental disorders. PMID:26260494

  16. A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders

    PubMed Central

    Geier, David A.; Hooker, Brian S.; Kern, Janet K.; King, Paul G.; Sykes, Lisa K.; Geier, Mark R.

    2014-01-01

    A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000) in the Vaccine Safety Datalink (VSD) project. ND cases were diagnosed with pervasive developmental disorder (PDD), specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV) administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR) = 1.054), specific developmental delay (OR = 1.035), tic disorder (OR = 1.034) and hyperkinetic syndrome of childhood (OR = 1.05) cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis. PMID:25198681

  17. A dose-response relationship between organic mercury exposure from thimerosal-containing vaccines and neurodevelopmental disorders.

    PubMed

    Geier, David A; Hooker, Brian S; Kern, Janet K; King, Paul G; Sykes, Lisa K; Geier, Mark R

    2014-09-01

    A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991-2000) in the Vaccine Safety Datalink (VSD) project. ND cases were diagnosed with pervasive developmental disorder (PDD), specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV) administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR) = 1.054), specific developmental delay (OR = 1.035), tic disorder (OR = 1.034) and hyperkinetic syndrome of childhood (OR = 1.05) cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis. PMID:25198681

  18. Responding to Requests of Families for Unproven Interventions in Neurodevelopmental Disorders: Hyperbaric Oxygen "Treatment" and Stem Cell "Therapy" in Cerebral Palsy

    ERIC Educational Resources Information Center

    Bell, Emily; Wallace, Tessa; Chouinard, Isabelle; Shevell, Michael; Racine, Eric

    2011-01-01

    Faced with the limitations of currently available mainstream medical treatments and interventions, parents of children with neurodevelopmental disorders often seek information about unproven interventions. These interventions frequently have undetermined efficacy and uncertain safety profiles. In this article, we present a general background and…

  19. The European Prader-Willi Syndrome Clinical Research Database: An Aid in the Investigation of a Rare Genetically Determined Neurodevelopmental Disorder

    ERIC Educational Resources Information Center

    Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.

    2009-01-01

    Background: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research…

  20. Targeted next-generation sequencing in the diagnosis of neurodevelopmental disorders.

    PubMed

    Okamoto, N; Miya, F; Tsunoda, T; Kato, M; Saitoh, S; Yamasaki, M; Shimizu, A; Torii, C; Kanemura, Y; Kosaki, K

    2015-09-01

    We developed a next-generation sequencing (NGS) based mutation screening strategy for neurodevelopmental diseases. Using this system, we screened 284 genes in 40 patients. Several novel mutations were discovered. Patient 1 had a novel mutation in ACTB. Her dysmorphic feature was mild for Baraitser-Winter syndrome. Patient 2 had a truncating mutation of DYRK1A. She lacked microcephaly, which was previously assumed to be a constant feature of DYRK1A loss of function. Patient 3 had a novel mutation in GABRD gene. She showed Rett syndrome like features. Patient 4 was diagnosed with Noonan syndrome with PTPN11 mutation. He showed complete agenesis of corpus callosum. We have discussed these novel findings. PMID:25156961

  1. Ethics in neurodevelopmental disability.

    PubMed

    Racine, Eric; Bell, Emily; Shevell, Michael

    2013-01-01

    Neurodevelopmental disabilities, like autism spectrum disorders and cerebral palsy are a common health problem in children. Given the impact of these conditions on children, families, and healthcare and social systems, the care of developmentally challenged children raises questions related to values and ethical principles. We review the common features of neurodevelopmental disorders that help understand the associated ethical questions. We focus on three major areas where ethical questions arise for clinicians and those involved in making decisions for or caring for these children: (1) the principles of decision-making and autonomy as they relate to developmental disability; (2) the issues related to quality of life that have long intersected with developmental disability; and (3) the use of unproven therapies and diagnostics that are particularly controversial given the extent that neurodevelopmental disabilities impact children and their families, yet active treatments options are limited. PMID:24182383

  2. Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part II: Palócs from Mátraderecske.

    PubMed

    Agarwal, D P; Benkmann, H G; Goedde, H W; Püschel, K; Béres, J; Czeizel, A E; Dobos, I; Métneki, J; Szekér, E; Sahegyi, J

    1995-03-01

    An epidemiological study on alcohol drinking habits, alcohol metabolism rate, alcohol-related acute physiological symptoms, and alcohol misuse among Palócs, an ethnic minority in Hungary, was conducted. The demographic and sociocultural correlates revealed their ethnic identity: low to moderate education, relatively low number of children per family and higher percentage of skilled workers among males. Alcohol use survey revealed that frequency of alcohol consumption among Palóc male population is considerably high. While about 41% of the Palóc males reported to drink daily between 30 ml and 90 ml pure alcohol, only 5% of the females reported to consume this amount regularly. 53% of males and less than 1% of females were classified as heavy drinkers (consuming more than 60 ml absolute alcohol per day). While all kinds of alcoholic beverage was reported to be consumed by the males, Pálinka (a kind of brandy) drinking was more common among females. About 45% of the Palócs reported to experience acute reactions after drinking a moderate dose of alcohol. The physical and physiological reactions include facial flushing, higher pulse rate, tachycardia and euphoria. While there was no distinct gender difference in facial flushing response to alcohol drinking, a higher percentage of males (70%) reported symptoms such as sleepiness, euphoria and aggressiveness as compared to about only 36% females reporting such reactions. Distribution of clinical chemical markers, in particular GGT values confirmed a heavier alcohol consumption among males than among females. High GGT value also correlated with a positive alcohol-related facial flushing reaction in males. PMID:7755376

  3. The Genetic Intersection of Neurodevelopmental Disorders and Shared Medical Comorbidities – Relations that Translate from Bench to Bedside

    PubMed Central

    Plummer, Jasmine T.; Gordon, Alexis J.; Levitt, Pat

    2016-01-01

    Most psychiatric disorders are considered neurodevelopmental, and the associated genes often are expressed in tissues outside of the brain. This suggests a biological relatedness with medical co-occurrences that could have broad clinical implications for diagnosis and patient management over a lifetime. A qualitative integration of public data from genetic consortia of psychiatric disorders and medical comorbidities explores the question of whether genetically associated psychiatric illnesses present with co-occurring disturbances can be used to define specific mental–physical health relations. Novel patterns of gene-disorder relations appear with approximately one-third of conservatively defined, consortia-generated candidate risk genes with multiple psychiatric diagnoses. Moreover, nearly as many genes overlap with non-psychiatric phenotypes, including cardiovascular, renal, respiratory, and metabolic disturbances. While the landscape of genetic risk will change as study populations are expanded and biological confirmations accrue, the current relationships suggest that a mostly siloed perspective of gene relatedness to one categorical psychiatric diagnosis is not clinically useful. The future holds the promise that once candidates are fully validated, genome screening and mutation identification will bring more precision for predicting the risk for complex health conditions. Our view is that as genetic data are refined, continuing to decipher a shared pattern of genetic risk for brain and peripheral organ pathophysiology is not simply an academic exercise. Rather, determining relatedness will impact predictions of multifaceted health risks, patient treatment, and management. PMID:27597832

  4. The Genetic Intersection of Neurodevelopmental Disorders and Shared Medical Comorbidities - Relations that Translate from Bench to Bedside.

    PubMed

    Plummer, Jasmine T; Gordon, Alexis J; Levitt, Pat

    2016-01-01

    Most psychiatric disorders are considered neurodevelopmental, and the associated genes often are expressed in tissues outside of the brain. This suggests a biological relatedness with medical co-occurrences that could have broad clinical implications for diagnosis and patient management over a lifetime. A qualitative integration of public data from genetic consortia of psychiatric disorders and medical comorbidities explores the question of whether genetically associated psychiatric illnesses present with co-occurring disturbances can be used to define specific mental-physical health relations. Novel patterns of gene-disorder relations appear with approximately one-third of conservatively defined, consortia-generated candidate risk genes with multiple psychiatric diagnoses. Moreover, nearly as many genes overlap with non-psychiatric phenotypes, including cardiovascular, renal, respiratory, and metabolic disturbances. While the landscape of genetic risk will change as study populations are expanded and biological confirmations accrue, the current relationships suggest that a mostly siloed perspective of gene relatedness to one categorical psychiatric diagnosis is not clinically useful. The future holds the promise that once candidates are fully validated, genome screening and mutation identification will bring more precision for predicting the risk for complex health conditions. Our view is that as genetic data are refined, continuing to decipher a shared pattern of genetic risk for brain and peripheral organ pathophysiology is not simply an academic exercise. Rather, determining relatedness will impact predictions of multifaceted health risks, patient treatment, and management. PMID:27597832

  5. Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder.

    PubMed

    Millan, Francisca; Cho, Megan T; Retterer, Kyle; Monaghan, Kristin G; Bai, Renkui; Vitazka, Patrik; Everman, David B; Smith, Brooke; Angle, Brad; Roberts, Victoria; Immken, LaDonna; Nagakura, Honey; DiFazio, Marc; Sherr, Elliott; Haverfield, Eden; Friedman, Bethany; Telegrafi, Aida; Juusola, Jane; Chung, Wendy K; Bale, Sherri

    2016-07-01

    Neurodevelopmental disorders (NDD) are common, with 1-3% of general population being affected, but the etiology is unknown in most individuals. Clinical whole-exome sequencing (WES) has proven to be a powerful tool for the identification of pathogenic variants leading to Mendelian disorders, among which NDD represent a significant percentage. Performing WES with a trio-approach has proven to be extremely effective in identifying de novo pathogenic variants as a common cause of NDD. Here we report six unrelated individuals with a common phenotype consisting of NDD with severe speech delay, hypotonia, and facial dysmorphism. These patients underwent WES with a trio approach and de novo heterozygous predicted pathogenic novel variants in the KAT6A gene were identified. The KAT6A gene encodes a histone acetyltransfrease protein and it has long been known for its structural involvement in acute myeloid leukemia; however, it has not previously been associated with any congenital disorder. In animal models the KAT6A ortholog is involved in transcriptional regulation during development. Given the similar findings in animal models and our patient's phenotypes, we hypothesize that KAT6A could play a role in development of the brain, face, and heart in humans. © 2016 Wiley Periodicals, Inc. PMID:27133397

  6. Editorial: Early detection of mental health and neurodevelopmental disorders: the ethical challenges of a field in its infancy.

    PubMed

    Ozonoff, Sally

    2015-09-01

    The signs of many mental health and neurodevelopmental conditions first appear in childhood and diagnosis can reliably be made by school age for most. Such conditions can be chronically disabling and confer significant long-term impairment. Determining early risk signs and first emerging symptoms of disorder is imperative to enhance early detection and to identify targets and ideal time points for prevention and intervention efforts. This Special Issue of JCPP focuses on the prospect of earlier identification of conditions that are traditionally diagnosed later in childhood. Ten invited empirical articles cover topics related to the science of early detection. Several are focused on prediction of later diagnosis, of functional impairment, and of future service utilization, while others cover instrument development and topics related to screening. The papers span the conditions of ADHD, ASD, dyslexia, mood dysregulation, disruptive behavior disorders, and anxiety disorders. This Editorial provides an overview of the invited contributions and the perspectives they provide on the ethical challenges and choices of a field still in its infancy. PMID:26257104

  7. Epigenetic factors in intellectual disability: the Rubinstein-Taybi syndrome as a paradigm of neurodevelopmental disorder with epigenetic origin.

    PubMed

    Lopez-Atalaya, Jose P; Valor, Luis M; Barco, Angel

    2014-01-01

    The number of genetic syndromes associated with intellectual disability that are caused by mutations in genes encoding chromatin-modifying enzymes has sharply risen in the last decade. We discuss here a neurodevelopmental disorder, the Rubinstein-Taybi syndrome (RSTS), originated by mutations in the genes encoding the lysine acetyltransferases CBP and p300. We first describe clinical and genetic aspects of the syndrome to later focus on the insight provided by the research in animal models of this disease. These studies have not only clarified the molecular etiology of RSTS and helped to dissect the developmental and adult components of the syndrome but also contributed to outline some important connections between epigenetics and cognition. We finally discuss how this body of research has opened new venues for the therapeutic intervention of this currently untreatable disease and present some of the outstanding questions in the field. We believe that the progress in the understanding of this rare disorder also has important implications for other intellectual disability disorders that share an epigenetic origin. PMID:25410544

  8. A neurodevelopmental framework for the development of interventions for children with fetal alcohol spectrum disorders

    PubMed Central

    Kodituwakku, Piyadasa W.

    2009-01-01

    Despite considerable data published on cognitive and behavioral disabilities in children with FASD, relatively little information is available on behavioral or pharmacological interventions for alcohol affected children. The main goals of this paper, therefore, are to summarize published intervention studies of FASD and to present a neurodevelopmental framework, based on recent findings from a number of disciplines, for designing new therapies for alcohol affected children. This framework assumes a neuroconstructionist view, which posits that reciprocal interactions between neural activity and the brain's hardware lead to the progressive formation of intra and inter-regional neural connections. In this view, behavioral interventions can be conceptualized as a series of guided experiences that are designed to produce neural activation. Based on evidence from cognitive neuroscience, it is hypothesized that specific interventions targeting executive attention and self-regulation may produce greater generalizable results than those aimed at domain specific skills in children with FASD. In view of reciprocal interactions between environmental effects and neural structures, the proposed framework suggests that the maximum effects of interventions can eventually be achieved by optimally combining behavioral methods and cognition enhancing drugs. PMID:20036485

  9. Novel neurodevelopmental disorder in the case of a giant occipitoparietal meningoencephalocele.

    PubMed

    Vogel, Timothy W; Manjila, Sunil; Cohen, Alan R

    2012-07-01

    Giant occipitoparietal encephaloceles are rare forms of neurodevelopmental defects whose etiologies remain uncertain. Their occurrence can lead to variable neurological outcomes depending on the extent of cerebral cortex involved and the ability to repair the defect. In addition, encephaloceles may be associated with various genetic syndromes and familial inheritance. Here, the authors describe a unique constellation of malformations associated with the case of a giant occipitoparietal meningoencephalocele with herniation of cortical tissue and continuity with the ventricular system. The patient had a cleft lip and palate, hemivertebrae of the thoracic spine, a patent ductus arteriosus, a ventricular septal defect, and coarctation of the aorta. To identify the genetic underpinnings of these malformations, fluorescence in situ hybridization and microarray analysis were performed and revealed an 80.65-kb gain within chromosome band 2p11.2. Duplications of this region involving RMND5A, whose product contains a C-terminal to lis homology (LisH) domain, have not previously been associated with a defined phenotype but may present insight into encephalocele formation. Surgical repair and follow-up for the neurological malformations are also discussed. PMID:22681319

  10. Adopting and Fostering Children with Fetal Alcohol Spectrum Disorders

    MedlinePlus

    ... clinical diagnosis. It refers to conditions such as fetal alcohol syndrome (FAS), alcohol- related neurodevelopmental disorder (ARND), and alcohol- ... Gossage, J.P. 2001. Estimating the prevalence of fetal alcohol syndrome: A summary. Alcohol Research & Health 25(3):159– ...

  11. Annual Research Review: Development of the Cerebral Cortex--Implications for Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Rubenstein, John L. R.

    2011-01-01

    The cerebral cortex has a central role in cognitive and emotional processing. As such, understanding the mechanisms that govern its development and function will be central to understanding the bases of severe neuropsychiatric disorders, particularly those that first appear in childhood. In this review, I highlight recent progress in elucidating…

  12. Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

    PubMed Central

    Arango, Celso

    2014-01-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  13. Differential neurodevelopmental trajectories in patients with early-onset bipolar and schizophrenia disorders.

    PubMed

    Arango, Celso; Fraguas, David; Parellada, Mara

    2014-03-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  14. Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders.

    PubMed

    Gillet, Virginie; Hunting, Darel John; Takser, Larissa

    2016-09-01

    The prevention of neurodevelopmental disorders (NDD) of prenatal origin suffers from the lack of objective tools for early detection of susceptible individuals and the long time lag, usually in years, between the neurotoxic exposure and the diagnosis of mental dysfunction. Human data on the effects of alcohol, lead, and mercury and experimental data from animals on developmental neurotoxins and their long-term behavioral effects have achieved a critical mass, leading to the concept of the Developmental Origin of Health and Disease (DOHaD). However, there is currently no way to evaluate the degree of brain damage early after birth. We propose that extracellular vesicles (EVs) and particularly exosomes, released by brain cells into the fetal blood, may offer us a non-invasive means of assessing brain damage by neurotoxins. We are inspired by the strategy applied by Alan Turing (a cryptanalyst working for the British government), who created a first computer to decrypt German intelligence communications during World War II. Given the growing evidence that microRNAs (miRNAs), which are among the molecules carried by EVs, are involved in cell-cell communication, we propose that decrypting messages from EVs can allow us to detect damage thus offering an opportunity to cure, reverse, or prevent the development of NDD. This review summarizes recent findings on miRNAs associated with selected environmental toxicants known to be involved in the pathophysiology of NDD. PMID:27301443

  15. Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders

    PubMed Central

    Suvisaari, Jaana; Brosi, Cornelia; Hennah, William; Leppä, Virpi; Torniainen, Minna; Ripatti, Samuli; Ala-Mello, Sirpa; Plöttner, Oliver; Rehnström, Karola; Tuulio-Henriksson, Annamari; Varilo, Teppo; Tallila, Jonna; Kristiansson, Kati; Isohanni, Matti; Kaprio, Jaakko; Eriksson, Johan G.; Raitakari, Olli T.; Lehtimäki, Terho; Jarvelin, Marjo-Riitta; Salomaa, Veikko; Hurles, Matthew; Stefansson, Hreinn; Peltonen, Leena; Sullivan, Patrick F.; Paunio, Tiina; Lönnqvist, Jouko; Daly, Mark J.; Fischer, Utz; Freimer, Nelson B.; Palotie, Aarno

    2014-01-01

    Implicating particular genes in the generation of complex brain and behavior phenotypes requires multiple lines of evidence. The rarity of most high impact genetic variants typically precludes the possibility of accruing statistical evidence that they are associated with a given trait. We show here that the enrichment of a rare Chromosome 22q11.22 deletion in a recently expanded Northern Finnish sub-isolate enables the detection of association between TOP3β and both schizophrenia and cognitive impairment. Biochemical analysis of TOP3β revealed that this topoisomerase is a component of cytosolic messenger ribonucleoproteins (mRNPs) and is catalytically active on RNA. The recruitment of TOP3β to mRNPs was independent of RNA cis-elements and was coupled to the co-recruitment of FMRP, the disease gene product in fragile X mental retardation syndrome (FXS). Thus, we uncover a novel role for TOP3β in mRNA metabolism and provide several lines of evidence implicating it in neurodevelopmental disorders. PMID:23912948

  16. Narrative retelling in children with neurodevelopmental disorders: is there a role for nonverbal temporal-sequencing skills?

    PubMed

    Johnels, Jakob Åsberg; Hagberg, Bibbi; Gillberg, Christopher; Miniscalco, Carmela

    2013-10-01

    Oral narrative retelling is often problematic for children with communicative and neurodevelopmental disorders. However, beyond a suggested role of language level, little is known about the basis of narrative performance. In this study we examine whether oral narrative retelling might be associated not just with language level but also with skills related to nonverbal narrative temporal sequencing. A diagnostically heterogeneous sample of Swedish-speaking children with a full scale IQ >70 was included in the study (N = 55; age 6-9 years). Narrative retelling skills were measured using the three subscores from the bus story test (BST). Independent predictors included (1) temporal sequencing skills according to a picture arrangement test and (2) a language skills factor consisting of definitional vocabulary and receptive grammar. Regression analyses show that language skills predicted BST Sentence Length and Subordinate Clauses subscores, while both temporal sequencing and language were independently linked with the BST Information subscore. When subdividing the sample based on nonverbal temporal sequencing level, a significant subgroup difference was found only for BST Information. Finally, a principal component analysis shows that temporal sequencing and BST Information loaded on a common factor, separately from the language measures. It is concluded that language level is an important correlate of narrative performance more generally in this diagnostically heterogeneous sample, and that nonverbal temporal sequencing functions are important especially for conveying story information. Theoretical and clinical implications are discussed. PMID:23855443

  17. Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives

    PubMed Central

    Deidda, Gabriele; Bozarth, Ignacio F.; Cancedda, Laura

    2014-01-01

    During mammalian ontogenesis, the neurotransmitter GABA is a fundamental regulator of neuronal networks. In neuronal development, GABAergic signaling regulates neural proliferation, migration, differentiation, and neuronal-network wiring. In the adult, GABA orchestrates the activity of different neuronal cell-types largely interconnected, by powerfully modulating synaptic activity. GABA exerts these functions by binding to chloride-permeable ionotropic GABAA receptors and metabotropic GABAB receptors. According to its functional importance during development, GABA is implicated in a number of neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis. The strength and polarity of GABAergic transmission is continuously modulated during physiological, but also pathological conditions. For GABAergic transmission through GABAA receptors, strength regulation is achieved by different mechanisms such as modulation of GABAA receptors themselves, variation of intracellular chloride concentration, and alteration in GABA metabolism. In the never-ending effort to find possible treatments for GABA-related neurological diseases, of great importance would be modulating GABAergic transmission in a safe and possibly physiological way, without the dangers of either silencing network activity or causing epileptic seizures. In this review, we will discuss the different ways to modulate GABAergic transmission normally at work both during physiological and pathological conditions. Our aim is to highlight new research perspectives for therapeutic treatments that reinstate natural and physiological brain functions in neuro-pathological conditions. PMID:24904277

  18. Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers

    PubMed Central

    Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby

    2013-01-01

    Background The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. Objective The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. Methods The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. Results A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome

  19. Perinatal Asphyxia Affects Rat Auditory Processing: Implications for Auditory Perceptual Impairments in Neurodevelopmental Disorders

    PubMed Central

    Strata, Fabrizio; Stoianov, Ivilin P.; de Villers-Sidani, Etienne; Bonham, Ben; Martone, Tiziana; Kenet, Tal; Chang, Edward F.; Vincenti, Vincenzo; Merzenich, Michael M.

    2010-01-01

    Perinatal asphyxia, a naturally and commonly occurring risk factor in birthing, represents one of the major causes of neonatal encephalopathy with long term consequences for infants. Here, degraded spectral and temporal responses to sounds were recorded from neurons in the primary auditory cortex (A1) of adult rats exposed to asphyxia at birth. Response onset latencies and durations were increased. Response amplitudes were reduced. Tuning curves were broader. Degraded successive-stimulus masking inhibitory mechanisms were associated with a reduced capability of neurons to follow higher-rate repetitive stimuli. The architecture of peripheral inner ear sensory epithelium was preserved, suggesting that recorded abnormalities can be of central origin. Some implications of these findings for the genesis of language perception deficits or for impaired language expression recorded in developmental disorders, such as autism spectrum disorders, contributed to by perinatal asphyxia, are discussed. PMID:21203459

  20. Targeting Glia with N-Acetylcysteine Modulates Brain Glutamate and Behaviors Relevant to Neurodevelopmental Disorders in C57BL/6J Mice

    PubMed Central

    Durieux, Alice M. S.; Fernandes, Cathy; Murphy, Declan; Labouesse, Marie Anais; Giovanoli, Sandra; Meyer, Urs; Li, Qi; So, Po-Wah; McAlonan, Grainne

    2015-01-01

    An imbalance between excitatory (E) glutamate and inhibitory (I) GABA transmission may underlie neurodevelopmental conditions such as autism spectrum disorder (ASD) and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here, we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC), which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviors relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span. PMID:26696857

  1. Genetic Risk for Attention-Deficit/Hyperactivity Disorder Contributes to Neurodevelopmental Traits in the General Population

    PubMed Central

    Martin, Joanna; Hamshere, Marian L.; Stergiakouli, Evangelia; O’Donovan, Michael C.; Thapar, Anita

    2014-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD) and ASD-related traits. The aims of this study were to determine whether a composite of common molecular genetic variants, previously found to be associated with clinically diagnosed ADHD, predicts ADHD and ASD-related traits in the general population. Methods Polygenic risk scores were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC) population sample (N = 8229) based on a discovery case-control genome-wide association study of childhood ADHD. Regression analyses were used to assess whether polygenic scores predicted ADHD traits and ASD-related measures (pragmatic language abilities and social cognition) in the ALSPAC sample. Polygenic scores were also compared in boys and girls endorsing any (rating ≥1) ADHD item (n = 3623). Results Polygenic risk for ADHD showed a positive association with ADHD traits (hyperactive-impulsive, p = .0039; inattentive, p = .037). Polygenic risk for ADHD was also negatively associated with pragmatic language abilities (p = .037) but not with social cognition (p = .43). In children with a rating ≥1 for ADHD traits, girls had a higher polygenic score than boys (p = .003). Conclusions These findings provide molecular genetic evidence that risk alleles for the categorical disorder of ADHD influence hyperactive-impulsive and attentional traits in the general population. The results further suggest that common genetic variation that contributes to ADHD diagnosis may also influence ASD-related traits, which at their extreme are a characteristic feature of ASD. PMID:24673882

  2. Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith-Magenis and Potocki-Lupski Syndromes.

    PubMed

    Neira-Fresneda, Juanita; Potocki, Lorraine

    2015-09-01

    Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are reciprocal contiguous gene syndromes within the well-characterized 17p11.2 region. Approximately 3.6 Mb microduplication of 17p11.2, known as PTLS, represents the mechanistically predicted homologous recombination reciprocal of the SMS microdeletion, both resulting in multiple congenital anomalies. Mouse model studies have revealed that the retinoic acid-inducible 1 gene (RAI1) within the SMS and PTLS critical genomic interval is the dosage-sensitive gene responsible for the major phenotypic features in these disorders. Even though PTLS and SMS share the same genomic region, clinical manifestations and behavioral issues are distinct and in fact some mirror traits may be on opposite ends of a given phenotypic spectrum. We describe the neurobehavioral phenotypes of SMS and PTLS patients during different life phases as well as clinical guidelines for diagnosis and a multidisciplinary approach once diagnosis is confirmed by array comparative genomic hybridization or RAI1 gene sequencing. The main goal is to increase awareness of these rare disorders because an earlier diagnosis will lead to more timely developmental intervention and medical management which will improve clinical outcome. PMID:27617127

  3. A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum Disorders, Including a Comparison with Other Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Atladóttir, H. Ó.; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.

    2015-01-01

    The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all…

  4. Conducting actigraphy research in children with neurodevelopmental disorders--a practical approach.

    PubMed

    Fawkes, Diane B; Malow, Beth A; Weiss, Shelly K; Reynolds, Ann M; Loh, Alvin; Adkins, Karen W; Wofford, Deborah D; Wyatt, Amanda D; Goldman, Suzanne E

    2015-01-01

    The literature has been highly informative for when to use actigraphy and its validity in pediatric research. However, minimal literature exists on how to perform actigraphy, especially in special populations. We determined whether providing actigraphy training to parents and coordinators increased the nights of actigraphy data that could be scored. We compared two studies in children with autism spectrum disorders, one of which provided a basic level of training in a single-site trial and the other of which provided more detailed training to parents and coordinators in a multisite trial. There was an increase in scorable nights in the multisite trial containing a one-hour structured parent training session. Our results support the use of educational tools in clinical trials that use actigraphy. PMID:24669845

  5. Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development.

    PubMed

    Hanamsagar, Richa; Bilbo, Staci D

    2016-06-01

    Several neurological conditions are associated with sex differences in prevalence or outcome. For example, autism predominantly affects boys, depression is more common in women, Parkinson's disease more common in men, and multiple sclerosis in women. In the case of stroke, women have a less favorable outcome and suffer from a more precipitous drop in health status compared to men. As a result, treatment of such diseases is difficult and yields variable results. Despite this, sex is rarely considered when making treatment decisions. The mechanisms underlying sex differences in disease progression are not well understood, however a strong link exists between different inflammation states of men and women and their propensity to develop certain diseases. As neuroinflammation is an important component of pathophysiology in many neurological conditions, it can be speculated that any changes in the state of inflammation in the brain during normal development can potentially lead to an increase in susceptibility to neurological and neurodegenerative diseases. Microglia play a crucial role in onset and modulation of inflammation and thus sex differences in microglial function could explain, at least in part, differences observed in susceptibilities and outcomes of neurological disorders in men and women. Understanding the mechanisms behind sex differences could help develop more targeted therapy with higher success rate, especially in diseases where sex differences are most prominent. PMID:26435451

  6. The Analysis of Genetic Aberrations in Children with Inherited Neurometabolic and Neurodevelopmental Disorders

    PubMed Central

    Szymańska, Krystyna; Ługowska, Agnieszka; Obersztyn, Ewa; Radkowski, Marek; Nowakowska, Beata A.; Kuśmierska, Katarzyna; Tryfon, Jolanta; Demkow, Urszula

    2014-01-01

    Inherited encephalopathies include a broad spectrum of heterogeneous disorders. To provide a correct diagnosis, an integrated approach including genetic testing is warranted. We report seven patients with difficult to diagnose inborn paediatric encephalopathies. The diagnosis could not be attained only by means of clinical and laboratory investigations and MRI. Additional genetic testing was required. Cytogenetics, PCR based tests, and array-based comparative genome hybridization were performed. In 4 patients with impaired language abilities we found the presence of microduplication in the region 16q23.1 affecting two dose-sensitive genes: WWOX (OMIM 605131) and MAF (OMIM 177075) (1 case), an interstitial deletion of the 17p11.2 region (2 patients further diagnosed as Smith-Magenis syndrome), and deletion encompassing first three exons of Myocyte Enhancer Factor gene 2MEF2C (1 case). The two other cases represented progressing dystonia. Characteristic GAG deletion in DYT1 consistently with the diagnosis of torsion dystonia was confirmed in 1 case. Last enrolled patient presented with clinical picture consistent with Krabbe disease confirmed by finding of two pathogenic variants of GALC gene and the absence of mutations in PSAP. The integrated diagnostic approach including genetic testing in selected examples of complicated hereditary diseases of the brain is largely discussed in this paper. PMID:24949445

  7. Visual sensorial impairments in neurodevelopmental disorders: evidence for a retinal phenotype in Fragile X Syndrome.

    PubMed

    Rossignol, Rafaëlle; Ranchon-Cole, Isabelle; Pâris, Arnaud; Herzine, Ameziane; Perche, Astrid; Laurenceau, David; Bertrand, Pauline; Cercy, Christine; Pichon, Jacques; Mortaud, Stéphane; Briault, Sylvain; Menuet, Arnaud; Perche, Olivier

    2014-01-01

    Visual sensory impairments are common in Mental Deficiency (MD) and Autism Spectrum Disorder (ASD). These defects are linked to cerebral dysfunction in the visual cortical area characterized by the deregulation of axon growth/guidance and dendrite spine immaturity of neurons. However, visual perception had not been addressed, although the retina is part of the central nervous system with a common embryonic origin. Therefore, we investigated retinal perception, the first event of vision, in a murine model of MD with autistic features. We document that retinal function is altered in Fmr1 KO mice, a model of human Fragile X Syndrome. Indeed, In Fmr1 KO mice had a lower retinal function characterized by a decreased photoreceptors neuron response, due to a 40% decrease in Rhodopsin content and to Rod Outer Segment destabilization. In addition, we observed an alteration of the visual signal transmission between photoreceptors and the inner retina which could be attributed to deregulations of pre- and post- synaptic proteins resulting in retinal neurons synaptic destabilization and to retinal neurons immaturity. Thus, for the first time, we demonstrated that retinal perception is altered in a murine model of MD with autistic features and that there are strong similarities between cerebral and retinal cellular and molecular defects. Our results suggest that both visual perception and integration must be taken into account in assessing visual sensory impairments in MD and ASD. PMID:25153086

  8. Mastication dyspraxia: a neurodevelopmental disorder reflecting disruption of the cerebellocerebral network involved in planned actions.

    PubMed

    Mariën, Peter; Vidts, Annelies; Van Hecke, Wim; De Surgeloose, Didier; De Belder, Frank; Parizel, Paul M; Engelborghs, Sebastiaan; De Deyn, Peter P; Verhoeven, Jo

    2013-04-01

    This paper reports the longitudinal clinical, neurocognitive, and neuroradiological findings in an adolescent patient with nonprogressive motor and cognitive disturbances consistent with a diagnosis of developmental coordination disorder (DCD). In addition to prototypical DCD, the development of mastication was severely impaired, while no evidence of swallowing apraxia, dysphagia, sensorimotor disturbances, abnormal tone, or impaired general cognition was found. He suffered from bronchopulmonary dysplasia and was ventilated as a newborn for 1.5 months. At the age of 3 months, a ventriculoperitoneal shunt was surgically installed because of obstructive hydrocephalus secondary to perinatal intraventricular bleeding. At the age of 5 years, the patient's attempts to masticate were characterized by rough, effortful, and laborious biting movements confined to the vertical plane. Solid food particles had a tendency to get struck in his mouth and there was constant spillage. As a substitute for mastication, he moved the unground food with his fingers in a lateral direction to the mandibular and maxillary vestibule to externally manipulate and squeeze the food between cheek and teeth with the palm of his hand. Once the food was sufficiently soft, the bolus was correctly transported by the tongue in posterior direction and normal deglutition took place. Repeat magnetic resonance imaging (MRI) during follow-up disclosed mild structural abnormalities as the sequelae of the perinatal intraventricular bleeding, but this could not explain impaired mastication behavior. Quantified Tc-99m-ethylcysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT), however, revealed decreased perfusion in the left cerebellar hemisphere, as well as in both inferior lateral frontal regions, both motor cortices, and the right anterior and lateral temporal areas. Anatomoclinical findings in this patient with DCD not only indicate that the functional integrity of the

  9. Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other neurodevelopmental syndromes associated with autism spectrum disorder.

    PubMed

    Mullegama, Sureni V; Alaimo, Joseph T; Chen, Li; Elsea, Sarah H

    2015-01-01

    Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5) is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention. PMID:25853262

  10. Neurodevelopmental and behavioural paediatrics.

    PubMed

    McDowell, Michael

    2015-01-01

    One of the notable shifts in Paediatrics across the last 50 years has been towards disorders that are chronic and qualitative in nature. In addition to physical health, these impact on childhood development, behaviour and wellbeing. Understanding and management of these problems extends the traditional biological toolkit of paediatrics into the complexities of uncertainties of psychological and social context. In Australasia, the profession has responded with the development of Community Paediatrics as a recognised sub-specialty, of which Neurodevelopmental and Behavioural Paediatrics is an important component. These developments are reviewed along with consideration of future challenges for this field of health care. PMID:25586854

  11. Alcohol-Related Problems of Older Persons.

    ERIC Educational Resources Information Center

    Staples, Pamela A.

    The study of older adults is relatively new for the social sciences. There is a growing awareness of the alcohol-related problems in this population. Between 2 and 10 percent of older social drinkers present severe alcohol-related problems of different kinds. Three terms describe the major consequences of "too much" alcohol: intoxication,…

  12. Chain reaction or time bomb: a neuropsychiatric-developmental/neurodevelopmental formulation of tourettisms, pervasive developmental disorder, and schizophreniform symptomatology associated with PANDAS.

    PubMed

    Kerbeshian, Jacob; Burd, Larry; Tait, Alison

    2007-01-01

    We present the case of a boy who over time sequentially exhibited symptoms consistent with a pervasive developmental disorder, schizophreniform symptomatology, multiple motor and vocal tics, and myoclonus. During this period he experienced multiple episodes of group A beta-haemolytic streptococcal (strep) infection confirmed by culture and serological studies. We speculate that paediatric autoimmune neuropsychiatric disorder associated with strep (PANDAS) may have served as an element in a complex chain of causation influencing the expression of his symptoms. Our main emphasis is to utilize our case study as an example of the application in case formulation of the neuropsychiatric developmental model and of the neurodevelopmental model on symptom ontogenesis and clinical outcome. PMID:17654411

  13. A novel maternally inherited 8q24.3 and a rare paternally inherited 14q23.3 CNVs in a family with neurodevelopmental disorders.

    PubMed

    Hu, Jie; Sathanoori, Malini; Kochmar, Sally; Azage, Meron; Mann, Susan; Madan-Khetarpal, Suneeta; Goldstein, Amy; Surti, Urvashi

    2015-08-01

    A 7-year-old female with developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), and seizures was referred to our laboratory for oligomicroarray analysis. The analysis revealed a 540 kb microdeletion in the chromosome 8q24.3 region (143,610,058-144,150,241) encompassing multiple genes. Two siblings of the proband were also analyzed. The proband's older sister with DD, seizures, and ASD has a 438 kb intragenic microdeletion of the GPHN gene in the chromosome 14q23.3 region (67,105,512-67,543,291) containing multiple exons, while the proband's older brother with DD, ASD, ID, and ADHD has both the 8q24.3 and the 14q23.3 deletions. All three siblings have a normal karyotype at the 650 G-band level of resolution. Parental FISH analysis indicates that the mother is a carrier for the 8q24.3 deletion and the father is a carrier for the 14q23.3 deletion. The 8q24.3 deletion seen in our patients has not been reported in the literature, while the small deletions of the 14q23.3 region involving multiple exons of the GPHN gene have been reported in a handful of patients in a recent study. The size of the 8q24.3 deletion and its genomic content, as well as the maternal family history, strongly suggest the association between the deletion and the neurodevelopmental disorders. Our study also provides more evidence in support of the association between GPHN deletion and neurodevelopmental disorders. PMID:25866352

  14. Alcohol-related dementia: an update of the evidence

    PubMed Central

    2013-01-01

    The characteristics of dementia relating to excessive alcohol use have received increased research interest in recent times. In this paper, the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and alcohol-induced persisting amnestic syndrome (Wernicke-Korsakoff syndrome, or WKS) are reviewed. Neuropathological and imaging studies suggest that excessive and prolonged use of alcohol may lead to structural and functional damage that is permanent in nature; however, there is debate about the relative contributions of the direct toxic effect of alcohol (neurotoxicity hypothesis), and the impact of thiamine deficiency, to lasting damage. Investigation of alcohol-related cognitive impairment has been further complicated by differing definitions of patterns of alcohol use and associated lifestyle factors related to the abuse of alcohol. Present diagnostic systems identify two main syndromes of alcohol-related cognitive impairment: ARD and WKS. However, 'alcohol-related brain damage' is increasingly used as an umbrella term to encompass the heterogeneity of these disorders. It is unclear what level of drinking may pose a risk for the development of brain damage or, in fact, whether lower levels of alcohol may protect against other forms of dementia. Epidemiological studies suggest that individuals with ARD typically have a younger age of onset than those with other forms of dementia, are more likely to be male, and often are socially isolated. The cognitive profile of ARD appears to involve both cortical and subcortical pathology, and deficits are most frequently observed on tasks of visuospatial function as well as memory and higher-order (executive) tasks. The WKS appears more heterogeneous in nature than originally documented, and deficits on executive tasks commonly are reported in conjunction with characteristic memory deficits. Individuals with alcohol-related disorders have the potential to at least

  15. Alcohol-related dementia: an update of the evidence.

    PubMed

    Ridley, Nicole J; Draper, Brian; Withall, Adrienne

    2013-01-01

    The characteristics of dementia relating to excessive alcohol use have received increased research interest in recent times. In this paper, the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and alcohol-induced persisting amnestic syndrome (Wernicke-Korsakoff syndrome, or WKS) are reviewed. Neuropathological and imaging studies suggest that excessive and prolonged use of alcohol may lead to structural and functional damage that is permanent in nature; however, there is debate about the relative contributions of the direct toxic effect of alcohol (neurotoxicity hypothesis), and the impact of thiamine deficiency, to lasting damage. Investigation of alcohol-related cognitive impairment has been further complicated by differing definitions of patterns of alcohol use and associated lifestyle factors related to the abuse of alcohol. Present diagnostic systems identify two main syndromes of alcohol-related cognitive impairment: ARD and WKS. However, 'alcohol-related brain damage' is increasingly used as an umbrella term to encompass the heterogeneity of these disorders. It is unclear what level of drinking may pose a risk for the development of brain damage or, in fact, whether lower levels of alcohol may protect against other forms of dementia. Epidemiological studies suggest that individuals with ARD typically have a younger age of onset than those with other forms of dementia, are more likely to be male, and often are socially isolated. The cognitive profile of ARD appears to involve both cortical and subcortical pathology, and deficits are most frequently observed on tasks of visuospatial function as well as memory and higher-order (executive) tasks. The WKS appears more heterogeneous in nature than originally documented, and deficits on executive tasks commonly are reported in conjunction with characteristic memory deficits. Individuals with alcohol-related disorders have the potential to at least

  16. [Alcohol-related problems in Cantabria].

    PubMed

    Gutiérrez Pérez, A M; Díez Manrique, J F; Peña Martín, C; García Usieto, E

    1995-01-01

    It is a cross sectorial epidemiological community survey into a random sample of 1,816 adult people. The objetivo of our work is to test the existence of some social-demographic variables that can be accumulated to the existence of alcohol related problems. We found that the men, the young people, with low socioeconomic level, and semiurban style of life have the highest risk of alcohol related problems. 48% of the sample men have recognized any alcohol related problems during the previous year to our study. The highest problem prevalence is associated to increased alcohol consumption. After all, there are many people with low alcohol consumption who have alcohol related problems. PMID:7717148

  17. Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, impaired adult social behavior and activity patterns

    PubMed Central

    Wise, Alexandra; Tenezaca, Luis; Fernandez, Robert W.; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F.; Venkatesh, Tadmiri

    2016-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions and hyperactivity. ASD exhibits a strong genetic component with underlying multi-gene interactions. Candidate gene studies have shown that the neurobeachin gene is disrupted in human patients with idiopathic autism (Castermans et al., 2003). The gene for neurobeachin (NBEA) spans the common fragile site FRA 13A and encodes a signal scaffold protein (Savelyeva et al., 2006). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. (Medrihan et al., 2009; Savelyeva, Sagulenko, Schmitt, & Schwab, 2006). rugose (rg) is the Drosophila homologue of the mammalian and human neurobeachin. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the EGFR and Notch mediated signaling pathways, facilitating cross-talk between these and other pathways (Shamloula et al., 2002). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion and hyperactivity. These results demonstrate that Drosophila neurobeachin (rugose) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying autism spectrum disorders. PMID:26100104

  18. Mental Health Disorders among Children within Child Welfare who have Prenatal Substance Exposure: Rural vs. Urban Populations.

    PubMed

    Chasnoff, Ira J; Telford, Erin; Wells, Anne M; King, Lauren

    2015-01-01

    This study analyzed differences in mental health diagnoses among Illinois child welfare-involved youth who have had prenatal substance exposure. Results indicate that youth from the rural area had a significantly higher rate of co-occurring mental health disorders. A multiple regression analysis revealed five significant predictors: living in a rural area, a history of neglect, having Fetal Alcohol Syndrome or an alcohol-related neurodevelopmental disorder, and age. These results have implications for adapting existing treatment models. PMID:26827476

  19. Cloning of the promoter of NDE1, a gene implicated in psychiatric and neurodevelopmental disorders through copy number variation.

    PubMed

    Bradshaw, N J

    2016-06-01

    Copy number variation at 16p13.11 has been associated with a range of neurodevelopmental and psychiatric conditions, with duplication of this region being more common in individuals with schizophrenia. A prominent candidate gene within this locus is NDE1 (Nuclear Distribution Element 1) given its known importance for neurodevelopment, previous associations with mental illness and its well characterized interaction with the Disrupted in Schizophrenia 1 (DISC1) protein. In order to accurately model the effect of NDE1 duplication, it is important to first gain an understanding of how the gene is expressed. The complex promoter system of NDE1, which produces three distinct transcripts, each encoding for the same full-length NDE1 protein (also known as NudE), was therefore cloned and tested in human cell lines. The promoter for the longest of these three NDE1 transcripts was found to be responsible for the majority of expression in these systems, with its extended 5' untranslated region (UTR) having a limiting effect on its expression. These results thus highlight and clone the promoter elements required to generate systems in which the NDE1 protein is exogenously expressed under its native promoter, providing a biologically relevant model of 16p13.11 duplication in major mental illness. PMID:26975893

  20. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin–Siris syndrome

    PubMed Central

    Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair

    2016-01-01

    Background SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin–Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. Methods We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. Results We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin–Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. Conclusions We thus propose that SOX11 deletion or mutation can present with a Coffin–Siris phenotype. PMID:26543203

  1. Alcohol Related Birth Defects: Implications for Education.

    ERIC Educational Resources Information Center

    Lamanna, Michael

    1982-01-01

    Discusses background and nature of alcohol-related birth defects. Describes a continuum of impairment to offspring of drinking mothers that is dose-related and produces serious behavioral/learning deficits. The continuum includes young people of normal intelligence who perform below expected levels and find school adjustment difficult. Offers…

  2. Simons Variation in Individuals Project (Simons VIP): a genetics-first approach to studying autism spectrum and related neurodevelopmental disorders.

    PubMed

    2012-03-22

    We describe a project aimed at studying a large number of individuals (>200) with specific recurrent genetic variations (deletion or duplication of segment 16p11.2) that increase the risk of developing autism spectrum (ASD) and other developmental disorders. The genetics-first approach augmented by web-based recruitment, multisite collaboration and calibration, and robust data-sharing policies could be adopted by other groups studying neuropsychiatric disorders to accelerate the pace of research. PMID:22445335

  3. Behavioral and Neurodevelopmental Precursors to Binge-Type Eating Disorders: Support for the Role of Negative Valence Systems

    PubMed Central

    Vannucci, Anna; Nelson, Eric E.; Bongiorno, Diana M.; Pine, Daniel S.; Yanovski, Jack A.; Tanofsky-Kraff, Marian

    2015-01-01

    Background Pediatric loss-of-control eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to loss-of-control eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions. Method We review evidence within constructs of the Negative Valence Systems (NVS)-domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating disorder risk. Results Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk-factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures. Conclusions We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of loss-of-control and binge-type eating disorders is required. PMID:26040923

  4. Clinical and pathological features of alcohol-related brain damage.

    PubMed

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD. PMID:21487421

  5. Effect of bisphenol A on Drosophila melanogaster behavior--a new model for the studies on neurodevelopmental disorders.

    PubMed

    Kaur, Kulbir; Simon, Anne F; Chauhan, Ved; Chauhan, Abha

    2015-05-01

    Developmental disorders such as autism and attention deficit hyperactivity disorder (ADHD) appear to have a complex etiology implicating both genetic and environmental factors. Bisphenol A (BPA), a widely used chemical in the plastic containers and in the linings of food and beverage cans, has been suggested to play a possible causative role in some developmental disorders. Here, we report behavioral modifications in Drosophila melanogaster following early exposure to BPA, which may suggest BPA as an environmental risk factor for the behavioral impairments that are the basis of diagnosis of autism and ADHD. In an open field assay with perinatally BPA-exposed and vehicle-treated control Drosophila, different parameters of locomotion (distance traveled, walking speed, spatial movement, mobility, turn angle, angular velocity and meander) were analyzed using the ethovision software. We also examined the repetitive and social interaction behaviors in these flies. In an open field assay, we identified disturbances in the locomotion patterns of BPA-exposed Drosophila that may relate to the decision-making and the motivational state of the animal. An increase in repetitive behavior was observed as an increase in the grooming behavior of Drosophila following BPA exposure. Furthermore, we also observed abnormal social interaction by the BPA-exposed flies in a social setting. These results demonstrate the effect of the environmentally prevalent risk agent BPA on the behavior of Drosophila, and suggest the practicability and the ease of using Drosophila as a model in the studies of neurobehavioral developmental disorders. PMID:25660202

  6. 14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders

    PubMed Central

    Xu, Xiangjun; Jaehne, Emily J.; Greenberg, Zarina; McCarthy, Peter; Saleh, Eiman; Parish, Clare L.; Camera, Daria; Heng, Julian; Haas, Matilda; Baune, Bernhard T.; Ratnayake, Udani; Buuse, Maarten van den; Lopez, Angel F.; Ramshaw, Hayley S.; Schwarz, Quenten

    2015-01-01

    Sequencing and expression analyses implicate 14-3-3ζ as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3ζ−/− mice in the Sv/129 background display schizophrenia-like defects. As epistatic interactions play a significant role in disease pathogenesis we generated a new congenic strain in the BALB/c background to determine the impact of genetic interactions on the 14-3-3ζ−/− phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3ζ−/− BALB/c mice identified enlarged lateral ventricles, reduced synaptic density and ectopically positioned pyramidal neurons in all subfields of the hippocampus. In contrast to our previous analyses, 14-3-3ζ−/− BALB/c mice lacked locomotor hyperactivity that was underscored by normal levels of the dopamine transporter (DAT) and dopamine signalling. Taken together, our results demonstrate that dysfunction of 14-3-3ζ gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3ζ-deficient BALB/c mice therefore provide a novel model to address the underlying biology of structural defects affecting the hippocampus and ventricle, and cognitive defects such as hippocampal-dependent learning and memory. PMID:26207352

  7. Countermeasures for Reducing Alcohol-Related Crashes.

    PubMed

    Voas, R B

    2000-01-01

    Programs to prevent alcohol-related crashes occur at several levels. Although most of the public thinks of drunk-driving prevention only in terms of the criminal justice system, much can be done to prevent alcohol-related highway deaths before the drinking-and-driving offender gets on the road. In recent years, the field of alcohol safety has merged with the area of public health concerned with preventing alcohol- and drug-related traumatic injury and death. This paper provides an overview of the status of road safety programs directed at reducing impaired driving. It covers ten topics falling into the three levels of prevention: primary programs to reduce alcohol consumption; secondary programs to prevent driving after drinking; and tertiary programs to prevent recidivism among convicted drinking drivers. PMID:26256029

  8. Translational Approaches for Studying Neurodevelopmental Disorders Utilizing in Vivo Proton (+H) Magnetic Resonance Spectroscopic Imaging in Rats

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2014-01-01

    Intrauterine complications have been implicated in the etiology of neuripsychiatric disorders including schizophrenia, autism and ADHD. This presentation will describe new translational studies derived from in vivo magnetic resonance imaging of developing and adult brain following perinatal asphyxia (PA). Our findings reveal significant effects of PA on neurometabolic profiles at one week of age, and significant relationships between early metabolites and later life phenotypes including behavior and brain morphometry

  9. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways

    PubMed Central

    Cappi, C; Brentani, H; Lima, L; Sanders, S J; Zai, G; Diniz, B J; Reis, V N S; Hounie, A G; Conceição do Rosário, M; Mariani, D; Requena, G L; Puga, R; Souza-Duran, F L; Shavitt, R G; Pauls, D L; Miguel, E C; Fernandez, T V

    2016-01-01

    Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular

  10. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways.

    PubMed

    Cappi, C; Brentani, H; Lima, L; Sanders, S J; Zai, G; Diniz, B J; Reis, V N S; Hounie, A G; Conceição do Rosário, M; Mariani, D; Requena, G L; Puga, R; Souza-Duran, F L; Shavitt, R G; Pauls, D L; Miguel, E C; Fernandez, T V

    2016-01-01

    Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein-protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10(-8) per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular

  11. Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.

    PubMed

    Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D' Amato, Francesca R; Battaglia, Marco

    2016-01-01

    Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice's respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders. PMID:27121911

  12. Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes

    PubMed Central

    Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D’ Amato, Francesca R.; Battaglia, Marco

    2016-01-01

    Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice’s respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders. PMID:27121911

  13. Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders.

    PubMed

    Moey, Ching; Hinze, Susan J; Brueton, Louise; Morton, Jenny; McMullan, Dominic J; Kamien, Benjamin; Barnett, Christopher P; Brunetti-Pierri, Nicola; Nicholl, Jillian; Gecz, Jozef; Shoubridge, Cheryl

    2016-03-01

    Copy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males. PMID:26059843

  14. Asian American Women and Alcohol-Related Problems: The Role of Multidimensional Feminine Norms.

    PubMed

    Iwamoto, Derek Kenji; Grivel, Margaux; Cheng, Alice; Clinton, Lauren; Kaya, Aylin

    2016-04-01

    Increasing rates of heavy episodic drinking (HED; four or more drinks in one sitting) and alcohol use disorders among young adult Asian American women signify the need to identify the risk and protective factors for HED and alcohol-related problems in this demographic. Multidimensional feminine norms, or the beliefs and expectations of what it means to be a woman, are theoretically relevant factors that may help elucidate within-group variability in HED and alcohol-related problems. The present study examined associations between nine salient feminine norms, HED, and alcohol-related problems among 398 second-generation Asian American college women. Our findings reveal that certain feminine norms are protective of HED and alcohol-related problems, while others are risk factors, even when controlling for well-established correlates of HED and alcohol-related problems, such as perceived peer drinking norms. The results elucidate the importance of multidimensional feminine norms and their relationship to HED and alcohol-related problems among the increasingly at-risk group, Asian American college women. PMID:25634626

  15. A neurodevelopmental approach to understanding memory processes among intellectually gifted youth with attention-deficit hyperactivity disorder.

    PubMed

    Whitaker, Ashley M; Bell, Terece S; Houskamp, Beth M; O'Callaghan, Erin T

    2015-01-01

    Intellectual giftedness is associated with strong strategic verbal memory while attention-deficit hyperactivity disorder (ADHD) is associated with strategic verbal memory deficits; however, no previous research has explored how this contradiction manifests in gifted populations with diagnoses of ADHD. The purpose of this study was to explore strategic verbal memory processes among intellectually gifted youth with and without ADHD to provide clarification regarding this specific aspect of neuropsychological functioning within this population. One hundred twenty-five youth completed neuropsychological evaluations including the Wechsler Intelligence Scale for Children-Fourth Edition and California Verbal Learning Test-Children's Version (CVLT-C). Results revealed significant differences between groups, with intellectually gifted youth with ADHD achieving lower T scores on CVLT-C Trials 1 through 5 compared with intellectually gifted youth without ADHD, and intellectually gifted youth with ADHD achieving higher T scores than youth of average intellectual abilities with ADHD. Additionally, repeated-measures analysis of variance revealed a main effect improvement among gifted youth with ADHD in short-delay recall when provided with organizational cues. Findings revealed new evidence about the role of twice exceptionality (specifically intellectual giftedness and ADHD) in strategic verbal memory and have important implications for parents, educators, psychologists and neuropsychologists, and other mental health professionals working with this population. PMID:24191777

  16. A Dichotomy of Information-Seeking and Information-Trusting: Stem Cell Interventions and Children with Neurodevelopmental Disorders.

    PubMed

    Sharpe, Kimberly; Di Pietro, Nina; Jacob, Karen J; Illes, Judy

    2016-08-01

    Parents and primary caregivers of children with Cerebral Palsy (CP) and Autism Spectrum Disorder (ASD) are faced with difficult treatment choices and management options for their children. The potential of stem cell technologies as an interventional strategy for CP and ASD has gained attention in the last decade. Information about these interventions varies in quality, resulting in a complex landscape for parent decision making for a child's care. Further complicating this landscape are clinics that advertise these interventions as a legitimate treatment for a fee. In this study, we surveyed individuals who considered taking their child with ASD or CP abroad for stem cell interventions on their use of different sources of stem cell related health information and their level of trust in these sources. Participants reported that while the Internet was their most frequent source of information, it was not well-trusted. Rather, information sources trusted most were researchers and the science journals in which they publish, other parents of children with CP and ASD, and healthcare providers. These findings highlight a dichotomy between information-seeking preferences and information-trusted sources. We discuss the challenges of health science communication and present innovative opportunities to increase communication with trusted and reliable sources as part of an integrated multi-pronged approach. PMID:27286955

  17. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    PubMed Central

    Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

  18. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

    PubMed

    Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea; Walters, James; Gawlick, Micha; Stöber, Gerald; Rees, Elliott; Martin, Joanna; Little, Rosie B; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Aleksic, Branko; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F; Gejman, Pablo V; Shi, Jianxin; Sanders, Alan R; Duan, Jubao; Willis, Joseph; Sisodiya, Sanjay; Costain, Gregory; Werge, Thomas M; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Girirajan, Santhosh D; Stefansson, Hreinn; Stefansson, Kari; O'Donovan, Michael C; Owen, Michael J; Bassett, Anne; Kirov, George

    2016-05-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

  19. Mortality from alcohol related disease in Italy.

    PubMed Central

    La Vecchia, C; Decarli, A; Mezzanotte, G; Cislaghi, C

    1986-01-01

    Trends in death certification rates from the five major alcohol related causes of death in Italy (cancers of the mouth or pharynx, oesophagus, larynx, liver and cirrhosis of the liver) were analysed over a period (1955-79) in which per capita alcohol consumption almost trebled. Age standardised mortality from liver cirrhosis almost doubled in males and increased over 70% in females. In males, mortality from cancers of the upper digestive or respiratory tract showed increases of between 27% and 44%, and liver cancer increased by over 100%. In the late 1970s, the four alcohol related cancer sites accounted for about 12% of all cancer deaths in males and 4.5% in females. Mortality from liver cirrhosis alone accounted for 4.8% of all deaths in males (9.2% of manpower years lost) and 2.3% in females (6.3% manpower years lost) in females. These figures were even higher in selected areas of north eastern Italy, where alcohol consumption is greater. In absolute terms, the upward trends observed correspond to about 10,000 excess deaths per year in the late 1970s compared with rates observed two decades earlier and are thus second only to the increase in tobacco related causes of death over the same calendar period. PMID:3772284

  20. Pediatric gliomas as neurodevelopmental disorders.

    PubMed

    Baker, Suzanne J; Ellison, David W; Gutmann, David H

    2016-06-01

    Brain tumors represent the most common solid tumor of childhood, with gliomas comprising the largest fraction of these cancers. Several features distinguish them from their adult counterparts, including their natural history, causative genetic mutations, and brain locations. These unique properties suggest that the cellular and molecular etiologies that underlie their development and maintenance might be different from those that govern adult gliomagenesis and growth. In this review, we discuss the genetic basis for pediatric low-grade and high-grade glioma in the context of developmental neurobiology, and highlight the differences between histologically-similar tumors arising in children and adults. GLIA 2016;64:879-895. PMID:26638183

  1. Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders.

    PubMed

    Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

    2015-04-01

    Neurodevelopmental impairment in the serotonergic system may be involved in autism spectrum disorder. Yokukansan is a traditional herbal remedy for restlessness and agitation in children, and mother-infant co-administration (MICA) to both the child and the nursing mother is one of the recommended treatment approaches. Recent studies have revealed the neuropharmacological properties of Yokukansan (YKS), including its 5-HT1A (serotonin) receptor agonistic effects. We investigated the influence of YKS treatment on behavior in a novel environment and on brain monoamine metabolism during the nursing period in an animal model of neurodevelopmental disorders, prenatally BrdU (5-bromo-2'-deoxyuridine)-treated rats (BrdU-rats). YKS treatment did not influence locomotor activity in BrdU-rats but reduced grooming in open-field tests. YKS treatment without MICA disrupted the correlation between locomotor behaviors and rearing and altered levels of serotonin and its metabolite in the cerebellum. These effects were not observed in the group receiving YKS treatment with MICA. These data indicate a direct pharmacological effect of YKS on the development of grooming behavior and profound effects on cerebellar serotonin metabolism, which is thought to be influenced by nursing conditions. PMID:25315739

  2. Alcohol-Related Brain Damage in Humans

    PubMed Central

    Erdozain, Amaia M.; Morentin, Benito; Bedford, Lynn; King, Emma; Tooth, David; Brewer, Charlotte; Wayne, Declan; Johnson, Laura; Gerdes, Henry K.; Wigmore, Peter; Callado, Luis F.; Carter, Wayne G.

    2014-01-01

    Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics. PMID:24699688

  3. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  4. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  5. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  6. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  7. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  8. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  9. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  10. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  11. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  12. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  13. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  14. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  15. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  16. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  17. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  18. Normative perceptions of alcohol-related consequences among college students.

    PubMed

    Brett, Emma I; Leavens, Eleanor L; Miller, Mary Beth; Lombardi, Nathaniel; Leffingwell, Thad R

    2016-07-01

    College students in the U.S. continue to drink in hazardous ways and experience a range of alcohol-related consequences. Personalized feedback interventions (PFIs), which often include normative components comparing personal drinking to that of similar peers, have been effective in reducing alcohol outcomes among college students. Though normative perceptions of the quantity and frequency of alcohol use have been examined in many studies, norms for alcohol-related consequences have received less attention. The current study examined self-other discrepancies (SODs) for alcohol-related consequences among college students. Participants overestimated how often alcohol-related consequences are experienced by other same-sex students on campus and rated consequences as more acceptable for others to experience than themselves. No differences in SODs were found between those who did and did not report alcohol use. Future studies should examine the efficacy of PFIs that incorporate normative feedback on alcohol-related consequences. PMID:26896561

  19. [Clinical application of neuroimaging to alcohol-related dementia].

    PubMed

    Matsui, Toshifumi; Sakurai, Hideki; Toyama, Tomomi; Yoshimura, Atsushi; Matsushita, Sachio; Higuchi, Susumu

    2012-06-01

    Alcohol-related dementia (ARD) is one of the most common dementing disorders in middle-aged people and occurs in heavy drinkers who are estimated to be 10 - 15 % of the adult men in a community. While the concept of ARD is multifactorial and includes all cognitive deficits in alcoholics, the central clinical manifestations are exemplified by Korsakoff's syndrome (KS), a persistent neuropsychiatric syndrome, characterized by amnesia and disorientation that is caused by thiamine deficiency along with excessive alcohol consumption. Antemortem detection of intracranial changes has been made possible by MRI and many studies have revealed that alcoholics have atrophic changes in frontal lobe, cerebellum, medial temporal lobe and hippocampus. However, these brain regions are vulnerable to excessive alcohol and seem to be independent of cognitive deficits in alcoholics. This review shows the regional differences in gray matter volumes between cognitively normal alcoholics and patients with KS. By employing a 3-dimensional MRI method for voxel-based morphometry that enables an automated, unbiased, comprehensive assessment, we demonstrate that parahippocampal/hippocampal atrophy is specific to KS and thalamic atrophy and the third ventricle enlargement are more severe in patients with KS than in cognitively normal alcoholics. PMID:22894053

  20. Protective Behavioral Strategies, Social Norms, and Alcohol-Related Outcomes

    PubMed Central

    Arterberry, Brooke J.; Smith, Ashley E.; Martens, Matthew P.; Cadigan, Jennifer M.; Murphy, James G.

    2014-01-01

    The present study examined the unique contributions of protective behavioral strategies and social norms in predicting alcohol-related outcomes. Participants were 363 students from a large public university in the Midwest who reported at least one binge-drinking episode (5+/4+ drinks for men/women in one sitting) in the past 30 days. Data were collected 1/2010–3/2011. We used SEM to test models where protective behavioral strategies (PBS) and social norms were predictors of both alcohol use and alcohol-related problems, after controlling for the effects of gender. Both PBS and descriptive norms had relationships with alcohol use. PBS also had a relationship with alcohol-related problems. Overall, the findings suggest that PBS and social norms have unique associations with distinct alcohol-related outcomes. PMID:25419202

  1. PTSD Symptoms, Emotion Dysregulation, and Alcohol-Related Consequences Among College Students with a Trauma History

    PubMed Central

    Tripp, Jessica C.; McDevitt-Murphy, Meghan E.; Avery, Megan L.; Bracken, Katherine L.

    2015-01-01

    Objective Posttraumatic stress disorder (PTSD), alcohol use, and alcohol-related consequences have been linked to emotion dysregulation. Sex differences exist in both emotion regulation dimensions and alcohol use patterns. This investigation examined facets of emotion dysregulation as potential mediators of the relationship between PTSD symptoms and alcohol-related consequences and whether differences may exist across sexes. Methods Participants included 240 college students with a trauma history who reported using alcohol within the past three months and completed measures of PTSD symptoms, emotion dysregulation, alcohol consumption, alcohol-related consequences, and negative affect. The six facets of emotion dysregulation were examined as mediators of the relationship between PTSD symptoms and alcohol-related consequences in the full sample and by sex. Results There were differences in sexes on several variables, with women reporting higher PTSD scores and Lack of Emotional Awareness. Men reported significantly higher drinks per week in a typical week and a heavy week. There were significant associations between the variables for the full sample, with PTSD showing associations with five facets of emotion dysregulation subscales: Impulse Control Difficulties when Upset, Difficulties Engaging in Goal-Directed Behavior, Nonacceptance of Emotional Responses, Lack of Emotional Clarity, and Limited Access to Emotion Regulation Strategies. Alcohol-related consequences were associated with four aspects of emotion dysregulation: Impulse Control Difficulties when Upset, Difficulties Engaging in Goal-Direct Behavior, Nonacceptance of Emotional Reponses, and Limited Access to Emotion Regulation Strategies. Two aspects of emotion regulation, Impulse Control Difficulties and Difficulties Engaging in Goal Directed Behavior, mediated the relationship between PTSD symptoms and alcohol-related consequences in the full sample, even after adjusting for the effects of negative affect

  2. Different Neurodevelopmental Symptoms Have a Common Genetic Etiology

    ERIC Educational Resources Information Center

    Pettersson, Erik; Anckarsäter, Henrik; Gillberg, Christopher; Lichtenstein, Paul

    2013-01-01

    Background: Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed…

  3. Sleep in children with neurodevelopmental disabilities.

    PubMed

    Angriman, Marco; Caravale, Barbara; Novelli, Luana; Ferri, Raffaele; Bruni, Oliviero

    2015-06-01

    This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families. PMID:25918987

  4. Alcohol and alcohol-related harm in China: policy changes needed.

    PubMed

    Tang, Yi-lang; Xiang, Xiao-jun; Wang, Xu-yi; Cubells, Joseph F; Babor, Thomas F; Hao, Wei

    2013-04-01

    In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China's policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China's current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization's global strategy to reduce the harmful use of alcohol. PMID:23599550

  5. Affordability of alcohol and alcohol-related mortality in Belarus.

    PubMed

    Razvodovsky, Yury E

    2013-01-01

    Alcohol abuse has numerous adverse health and social consequences. The consumer response to changes in alcohol affordability is an important issue on alcohol policy debates. Studies from many countries have shown an inverse relationship between alcohol prices and alcohol consumption in the population. There are, however, suggestions that increasing the price of alcohol by rising taxes may have limited effect on alcohol-related problems, associated with long-term heavy drinking. The aim of the present study was to evaluate the relationship between alcohol affordability and alcohol-related mortality rates in post-Soviet Belarus. For this purpose trends in alcohol-related mortality rates (mortality from liver cirrhosis, pancreatitis, alcoholism and alcohol psychoses) and affordability of vodka between 1990 and 2010 were compared. The time series analysis revealed that 1% increase in vodka affordability is associated with an increase in liver cirrhosis mortality of 0,77%, an increase in pancreatitis mortality of 0.53%, an increase in mortality from alcoholism and alcohol psychoses of 0,70%. The major conclusion emerging from this study is that affordability of alcohol is one of the most important predictor of alcohol-related problems in a population. These findings provide additional evidence that decreasing in affordability of alcohol is an effective strategy for reducing alcohol consumption and alcohol-related harm. PMID:23748944

  6. Neurodevelopmental model of schizophrenia: update 2012

    PubMed Central

    Rapoport, JL; Giedd, JN; Gogtay, N

    2012-01-01

    The neurodevelopmental model of schizophrenia, which posits that the illness is the end state of abnormal neurodevelopmental processes that started years before the illness onset, is widely accepted, and has long been dominant for childhood-onset neuropsychiatric disorders. This selective review updates our 2005 review of recent studies that have impacted, or have the greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis. New studies suggest that placental pathology could be a key measure in future prenatal high-risk studies. Both common and rare genetic variants have proved surprisingly diagnostically nonspecific, and copy number variants (CNVs) associated with schizophrenia are often also associated with autism, epilepsy and intellectual deficiency. Large post-mortem gene expression studies and prospective developmental multi-modal brain imaging studies are providing critical data for future clinical and high-risk developmental brain studies. Whether there can be greater molecular specificity for phenotypic characterization is a subject of current intense study and debate, as is the possibility of neuronal phenotyping using human pluripotent-inducible stem cells. Biological nonspecificity, such as in timing or nature of early brain development, carries the possibility of new targets for broad preventive treatments. PMID:22488257

  7. Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes.

    PubMed

    Lionel, Anath C; Tammimies, Kristiina; Vaags, Andrea K; Rosenfeld, Jill A; Ahn, Joo Wook; Merico, Daniele; Noor, Abdul; Runke, Cassandra K; Pillalamarri, Vamsee K; Carter, Melissa T; Gazzellone, Matthew J; Thiruvahindrapuram, Bhooma; Fagerberg, Christina; Laulund, Lone W; Pellecchia, Giovanna; Lamoureux, Sylvia; Deshpande, Charu; Clayton-Smith, Jill; White, Ann C; Leather, Susan; Trounce, John; Melanie Bedford, H; Hatchwell, Eli; Eis, Peggy S; Yuen, Ryan K C; Walker, Susan; Uddin, Mohammed; Geraghty, Michael T; Nikkel, Sarah M; Tomiak, Eva M; Fernandez, Bridget A; Soreni, Noam; Crosbie, Jennifer; Arnold, Paul D; Schachar, Russell J; Roberts, Wendy; Paterson, Andrew D; So, Joyce; Szatmari, Peter; Chrysler, Christina; Woodbury-Smith, Marc; Brian Lowry, R; Zwaigenbaum, Lonnie; Mandyam, Divya; Wei, John; Macdonald, Jeffrey R; Howe, Jennifer L; Nalpathamkalam, Thomas; Wang, Zhuozhi; Tolson, Daniel; Cobb, David S; Wilks, Timothy M; Sorensen, Mark J; Bader, Patricia I; An, Yu; Wu, Bai-Lin; Musumeci, Sebastiano Antonino; Romano, Corrado; Postorivo, Diana; Nardone, Anna M; Monica, Matteo Della; Scarano, Gioacchino; Zoccante, Leonardo; Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto; Antona, Vincenzo; Carella, Massimo; Zelante, Leopoldo; Cavalli, Pietro; Poggiani, Carlo; Cavallari, Ugo; Argiropoulos, Bob; Chernos, Judy; Brasch-Andersen, Charlotte; Speevak, Marsha; Fichera, Marco; Ogilvie, Caroline Mackie; Shen, Yiping; Hodge, Jennelle C; Talkowski, Michael E; Stavropoulos, Dimitri J; Marshall, Christian R; Scherer, Stephen W

    2014-05-15

    Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment. PMID:24381304

  8. Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes

    PubMed Central

    Lionel, Anath C.; Tammimies, Kristiina; Vaags, Andrea K.; Rosenfeld, Jill A.; Ahn, Joo Wook; Merico, Daniele; Noor, Abdul; Runke, Cassandra K.; Pillalamarri, Vamsee K.; Carter, Melissa T.; Gazzellone, Matthew J.; Thiruvahindrapuram, Bhooma; Fagerberg, Christina; Laulund, Lone W.; Pellecchia, Giovanna; Lamoureux, Sylvia; Deshpande, Charu; Clayton-Smith, Jill; White, Ann C.; Leather, Susan; Trounce, John; Melanie Bedford, H.; Hatchwell, Eli; Eis, Peggy S.; Yuen, Ryan K.C.; Walker, Susan; Uddin, Mohammed; Geraghty, Michael T.; Nikkel, Sarah M.; Tomiak, Eva M.; Fernandez, Bridget A.; Soreni, Noam; Crosbie, Jennifer; Arnold, Paul D.; Schachar, Russell J.; Roberts, Wendy; Paterson, Andrew D.; So, Joyce; Szatmari, Peter; Chrysler, Christina; Woodbury-Smith, Marc; Brian Lowry, R.; Zwaigenbaum, Lonnie; Mandyam, Divya; Wei, John; MacDonald, Jeffrey R.; Howe, Jennifer L.; Nalpathamkalam, Thomas; Wang, Zhuozhi; Tolson, Daniel; Cobb, David S.; Wilks, Timothy M.; Sorensen, Mark J.; Bader, Patricia I.; An, Yu; Wu, Bai-Lin; Musumeci, Sebastiano Antonino; Romano, Corrado; Postorivo, Diana; Nardone, Anna M.; Monica, Matteo Della; Scarano, Gioacchino; Zoccante, Leonardo; Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto; Antona, Vincenzo; Carella, Massimo; Zelante, Leopoldo; Cavalli, Pietro; Poggiani, Carlo; Cavallari, Ugo; Argiropoulos, Bob; Chernos, Judy; Brasch-Andersen, Charlotte; Speevak, Marsha; Fichera, Marco; Ogilvie, Caroline Mackie; Shen, Yiping; Hodge, Jennelle C.; Talkowski, Michael E.; Stavropoulos, Dimitri J.; Marshall, Christian R.; Scherer, Stephen W.

    2014-01-01

    Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3′-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment. PMID:24381304

  9. Alcohol-related advertisements in a college newspaper.

    PubMed

    Walfish, S; Stenmark, D E; Wentz, D; Myers, C; Linares, D

    1981-07-01

    The college newspaper is a powerful socializing force on the university campus. Within the general context of a university-based Alcohol Abuse Prevention Project, the present investigation examined alcohol related advertising in a college newspaper at one southern university. Ads were categorized into those: (1) promoting the responsible use of alcohol, (2) promoting the irresponsible use of alcohol, and (3) having a neutral content. Results indicated that a great deal of alcohol-related advertising was presented in this publication, and the majority of advertising did not promote responsible use of the beverage. The potential role of the community-oriented professional as an intervention strategist is discussed. PMID:7327776

  10. Use of Novel Technology-Based Techniques to Improve Alcohol-Related Outcomes in Clinical Trials

    PubMed Central

    Gurvich, Eugenia M.; Kenna, George A.; Leggio, Lorenzo

    2013-01-01

    With a better understanding of the biologic basis of alcohol dependence and the considerable financial burden of alcohol abuse and dependence, the number of alcohol-related clinical pharmacotherapy trials has been on the rise. Subsequently, the potential to find efficacious treatments is more promising. Unfortunately, alcohol-related trials face a number of challenges, as a result of the difficulties that arise from traditional and outdated methods to collect data and ensure medication adherence. Novel technology-based assessments, such as ecological momentary assessment, interactive voice response, transdermal sensor and medication-event monitoring system provide a prospective solution—albeit not without possible concerns—to the difficulties faced in alcohol-related clinical trials. Clinical trials are meant to define the efficacy of the treatment and to determine an effective and safe dosage. However, due to lack of adherence a drug could inappropriately or mistakenly be judged as ineffective for treating a specific disorder. The described technologies may be important tools to prevent false negatives in validating drug efficacy, to provide consistency in clinical trials and to improve available data regarding the study of pharmacotherapies for alcohol dependence. PMID:23955872

  11. Missouri Curriculum Guide for Alcohol-Related Traffic Offenders' Program.

    ERIC Educational Resources Information Center

    Pierce, Don; McClain, Robert

    This document contains the second edition of the Alcohol or Drug Related Traffic Offenders' Program (ARTOP) curriculum guide developed by the Missouri Department of Mental Health to reduce alcohol-related traffic offenses by presenting factual information about the physical effects of alcohol on the body and on driving skills. The materials…

  12. Alcohol-Related Content of Animated Cartoons: A Historical Perspective

    PubMed Central

    Klein, Hugh; Shiffman, Kenneth S.

    2013-01-01

    This study, based on a stratified (by decade of production) random sample of 1,221 animated cartoons and 4,201 characters appearing in those cartoons, seeks to determine the prevalence of alcohol-related content; how, if at all, the prevalence changed between 1930 and 1996 (the years spanned by this research); and the types of messages that animated cartoons convey about beverage alcohol and drinking in terms of the characteristics that are associated with alcohol use, the contexts in which alcohol is used in cartoons, and the reasons why cartoon characters purportedly consume alcohol. Approximately 1 cartoon in 11 was found to contain alcohol-related content, indicating that the average child or adolescent viewer is exposed to approximately 24 alcohol-related messages each week just from the cartoons that he/she watches. Data indicated that the prevalence of alcohol-related content declined significantly over the years. Quite often, alcohol consumption was shown to result in no effects whatsoever for the drinker, and alcohol use often occurred when characters were alone. Overall, mixed, ambivalent messages were provided about drinking and the types of characters that did/not consume alcoholic beverages. PMID:24350176

  13. Family Supports for Children Who Have Alcohol-Related Disabilities

    ERIC Educational Resources Information Center

    Brown, James D.

    2004-01-01

    Since the first publication on fetal alcohol syndrome appeared in the scientific literature over 30 years ago, there has been a great deal of research interest in the topic. This paper reviews findings within the past 10 years related to causes, frequency, and diagnosis of alcohol-related disabilities, before turning to the impact these…

  14. [ENT emergency treatment and alcohol related head and neck injuries].

    PubMed

    Teudt, I; Grundmann, T; Pueschel, K; Hogan, B; Leventli, B

    2013-08-01

    The spectrum of ENT-diseases can differ widely among emergency departments (ED) of different geographic regions. Especially in terms of head and neck trauma a higher number of injuries can be expected in large cities due to alcohol related violence.The ED of a large hospital situated in the center of Hamburg Germany was analysed for ENT-emergency treatments in 2011 retrospectively. Beside usual patient statistics, the study focused on alcohol related injuries with an ENT-surgeon involved. All data were compared to reports by other EDs in Germany and alcohol related costs were approximated for initiation of prevention programs in the future.2 339 ENT-patients were admitted to the ED. 19% of all patients used an ambulance whereas 80% reached the ED by private transportation. The majority of patients were between 21 and 30 years of age. For 143 of all trauma cases alcohol involvement was documented. Subanalysis revealed male dominance and a high use of ambulance transportation.The high number of traumata differs considerably from other ENT studies. One reason is the hospital's close proximity to all time party districts like "Reeperbahn" and the "Port of Hamburg". In those areas high amounts of alcohol ingestion takes place leading to more injuries at the head- and neck region. Theoretically financial resources would be plenty after the initiation of those programs as the severe costs for alcohol related medical treatment would decline. PMID:23568584

  15. Alcohol-related harm among university students in Hanoi, Vietnam

    PubMed Central

    Diep, Pham Bich; Knibbe, Ronald A.; Giang, Kim Bao; De Vries, Nanne

    2013-01-01

    Introduction and Aim This study examines the prevalence of and risk factors for alcohol-related harm and types of harm among medical students from Hanoi Medical University (Vietnam). Risk factors include aspects of drinking patterns and relevant socio-demographic variables. Study Design and Methods A cross-sectional study involving 1st to 6th year students (N=1216; response rate 96.5%). Of these, 210 students from each academic year were randomly selected from a sampling frame covering all students from each academic year. Data were collected using a questionnaire distributed in class by researchers. Drinkers completed 23 questions on alcohol-related harm categorized into: 1) ‘negative influence on daily activities’; 2) ‘social conflict’; 3) ‘loss of control, acute consequences, and withdrawal’; 4) ‘mental health conditions’; and 5) ‘physical and medical health problems’. Logistic and Poisson regression models were used to identify the predictors of alcohol-related harm and the amount of harm, respectively. Results The prevalence of alcohol use associated with at least one or more of the five types of harm was higher in men (81.8%) than in women (60.4%). In female and male students, the most common harm category was ‘loss of control, acute consequences, and withdrawal’ (51.8 and 75.6%, respectively), followed by ‘negative influence on daily activities’ (29.4 and 55.8%, respectively). Age, living away from home, and average number of standard drinks per occasion among male drinkers, and age and frequency of drinking per week among female drinkers were associated with alcohol-related harm. Conclusions These data suggest that alcohol-related harm represents a serious public health problem among young educated individuals in Vietnam. The risk factors indicate that prevention should be aimed at aspects of drinking patterns and specific subpopulations defined by gender, age, and (for men only) type of living situation. PMID:23374703

  16. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    ERIC Educational Resources Information Center

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  17. Perinatal Pitocin as an Early ADHD Biomarker: Neurodevelopmental Risk?

    ERIC Educational Resources Information Center

    Kurth, Lisa; Haussmann, Robert

    2011-01-01

    Objective: To investigate a potential relationship between coincidental increases in perinatal Pitocin usage and subsequent childhood ADHD onset in an attempt to isolate a specific risk factor as an early biomarker of this neurodevelopmental disorder. Method: Maternal labor/delivery and corresponding childbirth records of 172 regionally diverse,…

  18. Research Note: Patterns of Alcohol-Related Mortality in Russia

    PubMed Central

    Pridemore, William Alex; Kim, Sang-Weon

    2006-01-01

    The level of alcohol consumption in Russia is among the highest in the world and is often associated with a variety of problems in the country. Until recently, however, it was impossible to examine the health and social burdens associated with consumption in Russia due to Soviet secrecy surrounding vital statistics and health data related to alcohol and other topics. This study employed newly available mortality data to describe the demographic, temporal, and spatial patterns of mortality resulting directly from chronic and acute alcohol consumption in the country. The data reveal that in spite of high overall rates of alcohol-related mortality in Russia, levels of mortality vary considerably along these dimensions. Although descriptive in nature, the patterns of alcohol-related mortality in Russia presented here should provide initial observations with which to generate and test hypotheses concerning the causes and consequences of these patterns. PMID:16900263

  19. Neurodevelopmental sequelae associated with gray and white matter changes and their cellular basis: A comparison between Autism Spectrum Disorder, ADHD and dyslexia.

    PubMed

    Bennett, M R; Lagopoulos, J

    2015-11-01

    Many psychiatric diseases, such as major depression and schizophrenia, are accompanied by patterns of gray matter and white matter changes in the cortex that may be due to structural pathologies of synapses and their dendrites in the gray matter on the one hand and to pathologies in myelinating oligodendrocytes on the other. Here the possibility has been briefly examined that such a generalization might also hold for Autistic Spectrum Disorders (ASD). Evidence is presented that gray matter changes that accompany ASD may in fact reflect changes in synapses and subsequently of their dendrites, whereas those in the white matter reflect changes in myelination due to pathologies of oligodendrocytes. It is proposed that such structural pathologies during development provide a coherent biological model not only for the onset and course of ASD but also provide the basis for development and systematic evaluation of new treatment strategies. PMID:26456538

  20. Health and social consequences of an alcohol-related admission to critical care: a qualitative study

    PubMed Central

    McPeake, Joanne; Forrest, Ewan; Quasim, Tara; Kinsella, John; O'Neill, Anna

    2016-01-01

    Objective To examine the impact of critical care on future alcohol-related behaviour. Further, it aimed to explore patterns of recovery for patients with and without alcohol use disorders beyond the hospital environment. Design In-depth, semistructured interviews with participants (patients) 3–7 months post intensive care discharge. Setting The setting for this study was a 20-bedded mixed intensive care unit (ICU), in a large teaching hospital in Scotland. On admission, patients were allocated to one of the three alcohol groups: low risk, harmful/hazardous and alcohol dependency. Participants 21 participants who received mechanical ventilation for greater than 3 days were interviewed between March 2013 and June 2014. Interventions None. Measurements and main results Four themes which impacted on recovery from ICU were identified in this patient group: psychological resilience, support for activities of daily living, social support and cohesion and the impact of alcohol use disorders on recovery. Participants also discussed the importance of personalised goal setting and appropriate and timely rehabilitation for alcohol-related behaviours during the critical care recovery period. Conclusions There is a significant interplay between alcohol misuse and recovery from critical illness. This study has demonstrated that at present, there is a haphazard approach to rehabilitation for patients after ICU. A more targeted rehabilitation pathway for patients leaving critical care, with specific emphasis on alcohol misuse if appropriate, requires to be generated. PMID:27048633

  1. NEURODEVELOPMENTAL EFFECTS OF ENVIRONMENTAL EXPOSURES

    EPA Science Inventory

    Neurodevelopmental Effects of Environmental Exposures
    Sherry G. Selevan, Pauline Mendola, Deborah C. Rice (US EPA, Washington,
    DC)

    The nervous system starts development early in gestation and continues to develop through adolescence. Thus, critical windows of vuln...

  2. Neurodevelopmental care in the NICU.

    PubMed

    Aucott, Susan; Donohue, Pamela K; Atkins, Eileen; Allen, Marilee C

    2002-01-01

    Neurodevelopmental care, which is any NICU intervention undertaken to improve neurodevelopmental outcome, includes NICU design, nursing routines, nursing care plans, management of pain, feeding methods and, most importantly, encouraging parental involvement with their NICU infant. Recognition that sensory stimulation can overwhelm preterm infants and increase physiologic signs of stress led to attempts to reduce sensory input. More recent approaches judiciously add back soothing sensory input (e.g., therapeutic touch, soft music). Circadian light/dark cycles and physical activity improve preterm growth. Attention to infant positioning and handling affects physiologic variables and joint mobility, if not functional motor abilities. A highly organized system of care for NICU infants is Als' NIDCAP (i.e., Neonatal Individualized Developmental Care and Assessment Program). Although NIDCAP may reduce need for respiratory support and hospital length of stay, it does not significantly influence neurodevelopmental outcome at 2-3 years. Pain management includes benign interventions (e.g., nonnutritive sucking, oral glucose), but the prolonged use of narcotics must be balanced against the consequences of sedation and dependency. The foremost challenge for NICUs remains parent disenfranchisement. Kangaroo care, which involves parent/infant skin-to-skin contact, improves preterm growth, decreases nosocomial infections and may shorten hospital length of stay. A great deal of work needs to be done to identify and demonstrate efficacy of specific interventions and changes that humanize the NICU, encourage parental involvement, support infant development and optimize preterm neurodevelopmental outcomes. PMID:12454906

  3. Neurodevelopmental outcomes of infants born prematurely.

    PubMed

    Aylward, Glen P

    2014-01-01

    Long-term follow-up of infants born prematurely is necessary to determine neurodevelopmental outcomes, particularly with the expansion of interest from major disabilities to high prevalence/low severity dysfunctions. Models of pathogenesis include changes due to developmental disruptions and to injury, the magnitude and type of change influenced by the infant's age, and central nervous system recovery and reorganization. Alterations in neurogenesis, migration, myelination, cell death, and synaptogenesis occur even in the absence of insult. Despite increased knowledge regarding these processes, the functional significance of brain abnormalities is unclear. Because of methodologic problems in follow-up studies, it is difficult to characterize outcome definitively. Nonetheless, an acceptable degree of agreement across studies is found with regard to specific neurodevelopmental outcomes: motor/neurologic function, visuomotor integrative skills, IQ, academic achievement, language, executive function, and attention-deficit hyperactivity disorder/behavioral issues. In general, children born prematurely have more problems in these areas than do their normal birth weight counterparts. Suggestions for improved analyses and clarification of outcomes include use of cluster analysis, structural equation modeling, growth curve analysis, developmental epidemiologic approaches, and better control of background variables using risk indexes and factor scores. Better assessment techniques measuring functions documented to be at higher risk of problems are discussed. PMID:25007063

  4. Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders.

    PubMed

    Ayhan, Y; Abazyan, B; Nomura, J; Kim, R; Ladenheim, B; Krasnova, I N; Sawa, A; Margolis, R L; Cadet, J L; Mori, S; Vogel, M W; Ross, C A; Pletnikov, M V

    2011-03-01

    Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases. PMID:20048751

  5. Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms.

    PubMed

    Gamsiz, Ece D; Sciarra, Laura N; Maguire, Abbie M; Pescosolido, Matthew F; van Dyck, Laura I; Morrow, Eric M

    2015-07-01

    Autism spectrum disorder (ASD) is a group of highly genetic neurodevelopmental disorders characterized by language, social, cognitive, and behavioral abnormalities. ASD is a complex disorder with a heterogeneous etiology. The genetic architecture of autism is such that a variety of different rare mutations have been discovered, including rare monogenic conditions that involve autistic symptoms. Also, de novo copy number variants and single nucleotide variants contribute to disease susceptibility. Finally, autosomal recessive loci are contributing to our understanding of inherited factors. We will review the progress that the field has made in the discovery of these rare genetic variants in autism. We argue that mutation discovery of this sort offers an important opportunity to identify neurodevelopmental mechanisms in disease. The hope is that these mechanisms will show some degree of convergence that may be amenable to treatment intervention. PMID:26105128

  6. Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes.

    PubMed

    Nedic, Gordana; Perkovic, Matea Nikolac; Sviglin, Korona Nenadic; Muck-Seler, Dorotea; Borovecki, Fran; Pivac, Nela

    2013-01-10

    Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence. PMID:23023098

  7. Dysregulation of BDNF-TrkB signaling in developing hippocampal neurons by Pb(2+): implications for an environmental basis of neurodevelopmental disorders.

    PubMed

    Stansfield, Kirstie H; Pilsner, J Richard; Lu, Quan; Wright, Robert O; Guilarte, Tomás R

    2012-05-01

    Dysregulation of synaptic development and function has been implicated in the pathophysiology of neurodegenerative disorders and mental disease. A neurotrophin that has an important function in neuronal and synaptic development is brain-derived neurotrophic factor (BDNF). In this communication, we examined the effects of lead (Pb(2+)) exposure on BDNF-tropomyosin-related kinase B (TrkB) signaling during the period of synaptogenesis in cultured neurons derived from embryonic rat hippocampi. We show that Pb(2+) exposure decreases BDNF gene and protein expression, and it may also alter the transport of BDNF vesicles to sites of release by altering Huntingtin phosphorylation and protein levels. Combined, these effects of Pb(2+) resulted in decreased concentrations of extracellular mature BDNF. The effect of Pb(2+) on BDNF gene expression was associated with a specific decrease in calcium-sensitive exon IV transcript levels and reduced phosphorylation and protein expression of the transcriptional repressor methyl-CpG-binding protein (MeCP2). TrkB protein levels and autophosphorylation at tyrosine 816 were significantly decreased by Pb(2+) exposure with a concomitant increase in p75 neurotrophin receptor (p75(NTR)) levels and altered TrkB-p75(NTR) colocalization. Finally, phosphorylation of Synapsin I, a presynaptic target of BDNF-TrkB signaling, was significantly decreased by Pb(2+) exposure with no effect on total Synapsin I protein levels. This effect of Pb(2+) exposure on Synapsin I phosphorylation may help explain the impairment in vesicular release documented by us previously (Neal, A. P., Stansfield, K. H., Worley, P. F., Thompson, R. E., and Guilarte, T. R. (2010). Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: Potential role of N-Methyl-D-aspartate receptor (NMDAR) dependent BDNF signaling. Toxicol. Sci. 116, 249-263) because it controls vesicle movement from the reserve pool to the readily releasable pool. In

  8. Neurodevelopmental Problems in Non-Syndromic Craniosynostosis.

    PubMed

    Shim, Kyu-Won; Park, Eun-Kyung; Kim, Ju-Seong; Kim, Yong-Oock; Kim, Dong-Seok

    2016-05-01

    Craniosynostosis is the premature fusion of calvarial sutures, resulting in deformed craniofacial appearance. Hence, for a long time, it has been considered an aesthetic disorder. Fused sutures restrict growth adjacent to the suture, but compensatory skull growth occurs to accommodate the growing brain. The primary goal for the management of this craniofacial deformity has been to release the constricted skull and reform the distorted shape of the skull vault. However, the intellectual and behavioral prognosis of affected children has also been taken into consideration since the beginning of the modern era of surgical management of craniosynostosis. A growing body of literature indicates that extensive surgery, such as the whole-vault cranioplasty approach, would result in better outcomes. In addition, the age at treatment is becoming a major concern for optimal outcome in terms of cosmetic results as well as neurodevelopment. This review will discuss major concerns regarding neurodevelopmental issues and related factors. PMID:27226855

  9. Neurodevelopmental Problems in Non-Syndromic Craniosynostosis

    PubMed Central

    Shim, Kyu-Won; Park, Eun-Kyung; Kim, Ju-Seong; Kim, Yong-Oock

    2016-01-01

    Craniosynostosis is the premature fusion of calvarial sutures, resulting in deformed craniofacial appearance. Hence, for a long time, it has been considered an aesthetic disorder. Fused sutures restrict growth adjacent to the suture, but compensatory skull growth occurs to accommodate the growing brain. The primary goal for the management of this craniofacial deformity has been to release the constricted skull and reform the distorted shape of the skull vault. However, the intellectual and behavioral prognosis of affected children has also been taken into consideration since the beginning of the modern era of surgical management of craniosynostosis. A growing body of literature indicates that extensive surgery, such as the whole-vault cranioplasty approach, would result in better outcomes. In addition, the age at treatment is becoming a major concern for optimal outcome in terms of cosmetic results as well as neurodevelopment. This review will discuss major concerns regarding neurodevelopmental issues and related factors. PMID:27226855

  10. Immunologic and Neurodevelopmental Susceptibilities of Autism

    PubMed Central

    Pessah, Isaac N.; Seegal, Richard F.; Lein, Pamela J.; LaSalle, Janine; Yee, Benjamin K.; Van De Water, Judy; Berman, Robert F.

    2008-01-01

    Symposium 5 focused on research approaches that are aimed at understanding common patterns of immunological and neurological dysfunction contributing to neurodevelopmental disorders such as autism and ADHD. The session focused on genetic, epigenetic, and environmental factors that might act in concert to influence autism risk, severity and co-morbidities, and immunological and neurobiological targets as etiologic contributors. The immune system of children at risk of autism may be therefore especially susceptible to psychological stressors, exposure to chemical triggers, and infectious agents. Identifying early biomarkers of risk provides tangible approaches toward designing studies in animals and humans that yield a better understanding of environmental risk factors, and can help identify rational intervention strategies to mitigate these risks. PMID:18394707

  11. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

    PubMed Central

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

  12. Alcohol and alcohol-related harm in China: policy changes needed

    PubMed Central

    Tang, Yi-lang; Xiang, Xiao-jun; Wang, Xu-yi; Cubells, Joseph F; Babor, Thomas F

    2013-01-01

    Abstract In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China’s policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China’s current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization’s global strategy to reduce the harmful use of alcohol. PMID:23599550

  13. The Japanese society of alcohol-related problems.

    PubMed

    Maruyama, Katsuya; Higuchi, Susumu

    2004-04-01

    This paper presents an outline of the Japanese Society of Alcohol-Related Problems. The precursor of the Society was the Japan Alcoholism Treatment Research Group, inaugurated in 1979, by merging two local research groups in the Tokyo and Osaka areas, both of which were exclusive gatherings of psychiatrists associated with alcoholism clinics. The Research Group developed into the Society in 1992, as the number of participants including those from other medical professions increased yearly, and the subjects of the group widened to include all addictive behaviours. In reflecting the process of establishment, it is unique in many aspects as a scientific society. The Society is not a science-orientated body for presentation of new research findings. The main programme of the annual meeting is therefore a set of symposia in which members participate and discuss clinical and/or social problems arising from dependency on alcohol or drugs. Perhaps because of its content, the annual meeting is attended each year by the largest number of participants among all the societies in Japan concerned with alcohol and drugs. For the next several years, the Society's activities will be directed at (1) establishment of guidelines for early identification of and intervention in alcohol-related problems; (2) expansion of its membership to include those in related fields of medicine and non-medical professions; (3) improvement of the system of journal publication; and (4) creation of a system for timely adequate response to social problems associated with drugs and alcohol. PMID:15049741

  14. “I Will Take a Shot for Every ‘Like’ I Get on This Status”: Posting Alcohol-Related Facebook Content Is Linked to Drinking Outcomes

    PubMed Central

    Westgate, Erin C; Neighbors, Clayton; Heppner, Hannes; Jahn, Susanna; Lindgren, Kristen P

    2014-01-01

    Objective: This study investigated whether self-reports of alcohol-related postings on Facebook by oneself or one’s Facebook friends were related to common motives for drinking and were uniquely predictive of self-reported alcohol outcomes (alcohol consumption, problems, and cravings). Method: Pacific Northwest undergraduates completed a survey of alcohol outcomes, drinking motives, and alcoholrelated Facebook postings. Participants completed the survey online as part of a larger study on alcohol use and cognitive associations. Participants were randomly selected through the university registrar’s office and consisted of 1,106 undergraduates (449 men, 654 women, 2 transgender, 1 declined to answer) between the ages of 18 and 25 years (M = 20.40, SD = 1.60) at a large university in the Pacific Northwest. Seven participants were excluded from analyses because of missing or suspect data. Results: Alcohol-related postings on Facebook were significantly correlated with social, enhancement, conformity, and coping motives for drinking (all ps < .001). After drinking motives were controlled for, self–alcohol-related postings independently and positively predicted the number of drinks per week, alcohol-related problems, risk of alcohol use disorders, and alcohol cravings (all ps < .001). In contrast, friends’ alcohol-related postings only predicted the risk of alcohol use disorders (p < .05) and marginally predicted alcohol-related problems (p = .07). Conclusions: Posting alcohol-related content on social media platforms such as Facebook is associated with common motivations for drinking and is, in itself, a strong predictive indicator of drinking outcomes independent of drinking motives. Moreover, self-related posting activity appears to be more predictive than Facebook friends’ activity. These findings suggest that social media platforms may be a useful target for future preventative and intervention efforts. PMID:24766750

  15. Alcohol-related Cues Promote Automatic Racial Bias.

    PubMed

    Stepanova, Elena V; Bartholow, Bruce D; Saults, J Scott; Friedman, Ronald S

    2012-07-01

    Previous research has shown that alcohol consumption can increase the expression of race bias by impairing control-related processes. The current study tested whether simple exposure to alcohol-related images can also increase bias, but via a different mechanism. Participants viewed magazine ads for either alcoholic or nonalcoholic beverages prior to completing Payne's (2001) Weapons Identification Task (WIT). As predicted, participants primed with alcohol ads exhibited greater race bias in the WIT than participants primed with neutral beverages. Process dissociation analyses indicated that these effects were due to automatic (relative to controlled) processes having a larger influence on behavior among alcohol-primed relative to neutral-primed participants. Structural equation modeling further showed that the alcohol-priming effect was mediated by increases in the influence of automatic associations on behavior. These data suggest an additional pathway by which alcohol can potentially harm inter-racial interactions, even when no beverage is consumed. PMID:22798699

  16. Modeling neurodevelopmental cognitive deficits in tasks with cross-species translational validity.

    PubMed

    Cope, Z A; Powell, S B; Young, J W

    2016-01-01

    Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to 'develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures' in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross-species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains. PMID:26667374

  17. [What are the physician's role and responsibility in the law named "Basic Act on Measures against Alcohol-related Health Harm"?].

    PubMed

    Io, Aro; Yoshimoto, Hisashi

    2015-09-01

    Japan passed the national law "Basic Act on Measures against Alcohol-related Health Harm" on December 2013. This law is expected to prevent inappropriate drinking that leads to alcohol-related problems such as physical and mental disorder, drunk driving, suicide, domestic violence, child abuse, and poor work performance. The physician's responsibilities under this law are described as follows: i) to provide high quality and appropriate medical care concerning alcohol-related health harm; ii) to reduce or eliminate the consumption of alcohol, thus preventing the progression of alcohol-related health harm; and iii) to coordinate these efforts amongst medical institutions. Based on this law, we believe that Japanese physicians will have essential roles in achieving the goals of this law and that we can fulfill our responsibilities by observing the following aspects: a) changing our message to the patients from "drink sensibly and moderately" to "low-risk drinking; but any drinking has a risk of harm and low-risk drinking is not risk-free"; b) encouraging the spread and use of Screening, Brief Intervention, and Referral to Treatment (SBIRT); and c) establishing community healthcare systems for alcohol-related problems, including dementia in the elderly and during alcohol emergencies. PMID:26394525

  18. A human neurodevelopmental model for Williams syndrome.

    PubMed

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain. PMID:27509850

  19. Neurodevelopmental delay among children under the age of three years at immunization clinics in Lagos State, Nigeria – Preliminary report

    PubMed Central

    Bakare, Muideen O.; Bello-Mojeed, Mashudat A.; Munir, Kerim M.; Ogun, Oluwayemi C.; Eaton, Julian

    2016-01-01

    Late diagnosis and interventions characterize childhood neurodevelopmental disorders in Sub-Saharan Africa. This has negatively impacted on the prognosis of the children with neurodevelopmental disorders. This study examined the prevalence and pattern of neurodevelopmental delays among children under the age of 3 years attending immunization clinics in Lagos State, Nigeria and also affords opportunity of early follow-up and interventions, which had been documented to improve prognosis. The study involved two stage assessments; which consisted of first phase screening of the children for neurodevelopmental delays in immunization clinics at primary healthcare centers Lagos State, Nigeria and second phase which consists of definitive clinical evaluation and follow-up interventions for children screened positive for neurodevelopmental delays. Twenty seven (0.9%) of a total of 3,011 children under the age of 3 years were screened positive for neurodevelopmental delays and subsequently undergoing clinical evaluation and follow-up interventions. Preliminary working diagnoses among these children include cerebral palsy, autism spectrum disorder trait, nutritional deficiency, Down syndrome and Non-specific neurodevelopmental delay with co-morbid seizure disorder accounting for 33.3%, 14.8%, 18.5%, 7.4% and 25.9% respectively. This is a preliminary report that would be followed up with information on medium and long term intervention phase. PMID:27125631

  20. Neurodevelopmental delay among children under the age of three years at immunization clinics in Lagos State, Nigeria - Preliminary report.

    PubMed

    Bakare, Muideen O; Bello-Mojeed, Mashudat A; Munir, Kerim M; Ogun, Oluwayemi C; Eaton, Julian

    2016-01-01

    Late diagnosis and interventions characterize childhood neurodevelopmental disorders in Sub-Saharan Africa. This has negatively impacted on the prognosis of the children with neurodevelopmental disorders. This study examined the prevalence and pattern of neurodevelopmental delays among children under the age of 3 years attending immunization clinics in Lagos State, Nigeria and also affords opportunity of early follow-up and interventions, which had been documented to improve prognosis. The study involved two stage assessments; which consisted of first phase screening of the children for neurodevelopmental delays in immunization clinics at primary healthcare centers Lagos State, Nigeria and second phase which consists of definitive clinical evaluation and follow-up interventions for children screened positive for neurodevelopmental delays. Twenty seven (0.9%) of a total of 3,011 children under the age of 3 years were screened positive for neurodevelopmental delays and subsequently undergoing clinical evaluation and follow-up interventions. Preliminary working diagnoses among these children include cerebral palsy, autism spectrum disorder trait, nutritional deficiency, Down syndrome and Non-specific neurodevelopmental delay with co-morbid seizure disorder accounting for 33.3%, 14.8%, 18.5%, 7.4% and 25.9% respectively. This is a preliminary report that would be followed up with information on medium and long term intervention phase. PMID:27125631

  1. Latent class analysis of alcohol treatment utilization patterns and 3-year alcohol related outcomes.

    PubMed

    Mowbray, Orion; Glass, Joseph E; Grinnell-Davis, Claudette L

    2015-07-01

    People who obtain treatment for alcohol use problems often utilize multiple sources of help. While prior studies have classified treatment use patterns for alcohol use, an empirical classification of these patterns is lacking. For the current study, we created an empirically derived classification of treatment use and described how these classifications were prospectively associated with alcohol-related outcomes. Our sample included 257 participants of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who first received alcohol treatment in the 3-year period prior to their baseline interview. We used latent class analysis to identify classes of treatment users based on their patterns of treatment use of 13 types of alcohol treatment. Regression models examined how classes of treatment use at baseline were associated with alcohol-related outcomes assessed at a 3-year follow-up interview. Outcomes included a continuous measure of the quantity and frequency of alcohol use and DSM-IV alcohol use disorder status. Four classes of treatment users were identified: (1) multiservice users (8.7%), (2) private professional service users (32.8%), (3) alcoholics anonymous (AA) paired with specialty addiction service users (22.0%), and (4) users of AA alone (36.5%). Those who utilized AA paired with specialty addiction services had better outcomes compared to those who used AA alone. In addition to elucidating the most common treatment utilization patterns executed by people seeking help for their alcohol problems, the results from this study suggest that increased efforts may be needed to refer individuals across sectors of care to improve treatment outcomes. PMID:25744651

  2. Detecting alcohol-related problems in developing countries: A comparison of two screening measures in India

    PubMed Central

    Nayak, Madhabika B.; Bond, Jason C.; Cherpitel, Cheryl; Patel, Vikram; Greenfield, Thomas K.

    2009-01-01

    Background There is inadequate recognition of alcohol misuse as a public health issue in India. Information on screening measures is critical for prevention and early intervention efforts. This study critically evaluated the full and shorter versions of the AUDIT and RAPS4-QF as screening measures for alcohol use disorders (AUDs) in a community sample of male drinkers in Goa, India. Methods Data from male drinking respondents in a population study on alcohol use patterns and sexual risk behaviors in randomly selected rural and urban areas of North Goa are reported. Overall, 39% (n=743) of the 1899 screened men, age 18 to 49, reported consuming alcohol in the last 12 months. These current drinkers were administered the screening measures as part of detailed interviews on drinking patterns and AUD symptoms. Receiver Operating Characteristic (ROC) analysis was conducted for each combination of screening measure and criterion (alcohol dependence or any AUD). Reliability and correlations among the 4 measures were also examined. Results All four measures performed well with area under the curves (AUCs) of at least .79. The full screeners that included both drinking patterns and problem items (the AUDIT and the RAP4-QF) performed better than their shorter versions (the AUDIT-C and the RAPS4) in detecting AUDs. Performance of the AUDIT and RAPS4-QF improved with lowered and raised thresholds, respectively, and alternate cut-off scores are suggested. Scores on the full measures were significantly correlated (.80). Reliability estimates for the AUDIT measures were higher than those for the RAPS4 measures. Conclusions All measures were efficient at detecting AUDs. When screening for alcohol-related problems among males in the general population in India, cut-off scores for screeners may need to be adjusted. Selecting an appropriate screening measure and cut-off score necessitates careful consideration of the screening context and resources available to confirm alcohol-related

  3. Exposure to Alcohol Advertisements and Teenage Alcohol-Related Problems

    PubMed Central

    Dent, Clyde W.; Stacy, Alan W.

    2013-01-01

    OBJECTIVE: This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. METHODS: A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents’ jobs, and parents’ education. RESULTS: Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. CONCLUSIONS: Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence. PMID:23359585

  4. Long-term neurodevelopmental follow-up of children with congenital muscular torticollis.

    PubMed

    Schertz, Mitchell; Zuk, Luba; Green, Dido

    2013-10-01

    Congenital muscular torticollis is a common condition, but long-term neurodevelopmental follow-up is lacking. This study reports on neurodevelopmental outcome of 68 children, aged 7 to 9 years, with a history of congenital muscular torticollis, excluding children with torticollis due to other conditions. Thirty-eight children were examined for presence of neurodevelopmental disorders. Telephone interview data were available for an additional 30 children. Of those examined, 22/38 (57.9%) had or were at risk for a developmental disorder (attention-deficit hyperactivity disorder (ADHD), developmental coordination disorder, language impairment, autistic spectrum disorder) on at least 1 of the assessments administered, 23/38 (60.5%) had received developmental treatment during childhood. One child, based on a telephone interview, had a history of developmental treatment. Therefore, 30/68 (44.1%) children of the total sample demonstrated a developmental delay/disorder, currently (22/68) or previously (8/68). Our findings suggest congenital muscular torticollis to be a significant risk factor for later neurodevelopmental conditions with disorders presenting at different stages of development. PMID:22952314

  5. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    PubMed Central

    Brand, Rhonda M.; Stottlemyer, John Mark; Cline, Rachel A.; Donahue, Cara; Behari, Jaideep; Falo, Louis D.

    2015-01-01

    Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. PMID:26561838

  6. Seasonality of alcohol-related phenomena in Estonia

    NASA Astrophysics Data System (ADS)

    Silm, Siiri; Ahas, Rein

    2005-03-01

    We studied alcohol consumption and its consequences as a seasonal phenomenon in Estonia and analysed the social and environmental factors that may cause its seasonal rhythm. There are two important questions when researching the seasonality of human activities: (1) whether it is caused by natural or social factors, and (2) whether the impact of the factors is direct or indirect. Often the seasonality of social phenomena is caused by social factors, but the triggering mechanisms are related to environmental factors like temperature, precipitation, and radiation via the circannual calendar. The indicators of alcohol consumption in the current paper are grouped as: (1) pre-consumption phenomena, i.e. production, tax and excise, sales (beer, wine and vodka are analysed separately), and (2) post-consumption phenomena, i.e. alcohol-related crime and traffic accidents and the number of people detained in lockups and admitted to alcohol treatment clinics. In addition, seasonal variability in the amount of alcohol advertising has been studied, and a survey has been carried out among 87 students of Tartu University. The analysis shows that different phenomena related to alcohol have a clear seasonal rhythm in Estonia. The peak period of phenomena related to beer is in the summer, from June to August and the low point is during the first months of the year. Beer consumption correlates well with air temperature. The consumption of vodka increases sharply at the end of the year and in June; the production of vodka does not have a significant correlation with negative temperatures. The consumption of wine increases during summer and in December. The consequences of alcohol consumption, expressed as the rate of traffic accidents or the frequency of medical treatment, also show seasonal variability. Seasonal variability of alcohol consumption in Estonia is influenced by natural factors (temperature, humidity, etc.) and by social factors (celebrations, vacations, etc.). However

  7. Social anxiety and alcohol-related impairment: The mediational impact of solitary drinking.

    PubMed

    Buckner, Julia D; Terlecki, Meredith A

    2016-07-01

    Social anxiety disorder more than quadruples the risk of developing an alcohol use disorder, yet it is inconsistently linked to drinking frequency. Inconsistent findings may be at least partially due to lack of attention to drinking context - it may be that socially anxious individuals are especially vulnerable to drinking more often in specific contexts that increase their risk for alcohol-related problems. For instance, socially anxious persons may drink more often while alone, before social situations for "liquid courage" and/or after social situations to manage negative thoughts about their performance. Among current (past-month) drinkers (N=776), social anxiety was significantly, positively related to solitary drinking frequency and was negatively related to social drinking frequency. Social anxiety was indirectly (via solitary drinking frequency) related to greater past-month drinking frequency and more drinking-related problems. Social anxiety was also indirectly (via social drinking frequency) negatively related to past-month drinking frequency and drinking-related problems. Findings suggest that socially anxious persons may be vulnerable to more frequent drinking in particular contexts (in this case alone) and that this context-specific drinking may play an important role in drinking problems among these high-risk individuals. PMID:26894561

  8. Disregulated Alcohol-Related Behavior among College Drinkers: Associations with Protective Behaviors, Personality, and Drinking Motives

    ERIC Educational Resources Information Center

    Isaak, Matthew I.; Perkins, David R.; Labatut, Tiffany R.

    2011-01-01

    Objective: This study investigated the psychometric properties of the Disregulated Alcohol-Related Behaviors Inventory (DARBI), a measure of harmful alcohol-related behavior, and the relationship between protective behavior use and scores on the DARBI and several other measures. Participants: Participants were 281 undergraduate volunteers (60%…

  9. Alcohol-Related Consequences among Intercollegiate Student Athletes: The Role of Drinking Motives

    ERIC Educational Resources Information Center

    Doumas, Diana M.

    2013-01-01

    This study examined drinking motives as predictors of alcohol-related consequences among student athletes and nonathletes. Results indicated that the highest level of alcohol-related consequences was reported by student athletes with high levels of both coping and conformity motives. (Contains 2 tables and 2 figures.)

  10. Demographic and Academic Trends in Drinking Patterns and Alcohol-Related Problems on Dry College Campuses

    ERIC Educational Resources Information Center

    Taylor, Dexter M.; Johnson, Mark B.; Voas, Robert B.; Turrisi, Robert

    2006-01-01

    Restricting alcohol consumption on campus is a measure often used by college administrators to prevent alcohol abuse and-alcohol-related problems. The effect of dry campus policies on alcohol consumption and alcohol-related problems, however, remains poorly understood. This report will compare characteristics of two dry campuses with descriptions…

  11. Neurodevelopmental problems in maltreated children referred with indiscriminate friendliness.

    PubMed

    Kočovská, Eva; Puckering, Christine; Follan, Michael; Smillie, Maureen; Gorski, Charlotta; Barnes, James; Wilson, Philip; Young, David; Lidstone, Emma; Pritchett, Rachel; Hockaday, Harriet; Minnis, Helen

    2012-01-01

    We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological families. All 66 children, aged 5-12 years, underwent a detailed neuropsychiatric assessment. The overwhelming majority of the adopted/indiscriminately friendly group had a range of psychiatric diagnoses, including Attention Deficit Hyperactivity Disorder (ADHD), Post-Traumatic Stress Disorder (PTSD) and Reactive Attachment Disorder (RAD) and one third exhibited the disorganised pattern of attachment. The mean IQ was 15 points lower than the comparison group and the majority of the adopted group had suspected language disorder and/or delay. Our findings show that school-aged adopted children with a history of severe maltreatment can have very complex and sometimes disabling neuropsychiatric problems. PMID:22522215

  12. Community off-sales provision and the presence of alcohol-related detritus in residential neighbourhoods.

    PubMed

    Forsyth, Alasdair J M; Davidson, Neil

    2010-03-01

    This paper investigates the relationship between community off-sales premises and alcohol-related detritus (litter/remains) in residential neighbourhoods. This was accomplished by photographing all brand-identifiable alcohol product detritus (glass, packaging, etc.) where they lay and mapping these against the presence of off-sales outlets (licensed convenience stores) in the community. It was hypothesised that alcohol-related detritus would be greatest near to such alcohol outlets. However, although there was some evidence of a "broken bottles effect", accumulations of alcohol-related detritus near some off-sales premises, it is concluded that local area deprivation is a better predictor of such alcohol-related incivility than is outlet provision. The implications of these findings are discussed in relation to current social responsibility policy developments which are designed to make the alcohol industry liable for alcohol-related incivilities. PMID:20004129

  13. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. PMID:26482673

  14. Alcohol craving and demand mediate the relation between posttraumatic stress symptoms and alcohol-related consequences.

    PubMed

    Tripp, Jessica C; Meshesha, Lidia Z; Teeters, Jenni B; Pickover, Alison M; McDevitt-Murphy, Meghan E; Murphy, James G

    2015-10-01

    Posttraumatic stress (PTS) symptoms are associated with alcohol-related consequences, but there is a need to understand mediators that may help explain the reasons for this relationship. Individuals with PTS may experience elevated craving and alcohol reward value (demand), which may contribute to risk for alcohol-related consequences. We examined relationships between PTS status, craving, alcohol demand, and alcohol-related consequences in PTS-positive (n = 64) and PTS-negative (n = 200) college students (M age = 21.7; 77% women; 54% Caucasian; 34% African American) who endorsed past-month alcohol use. We tested craving and alcohol demand as mediators of the relation between PTS status and alcohol-related consequences. Craving (B = .04, SE = .02, 95% CI [.01, .10]), demand intensity (B = .02, SE = .02, 95% CI [.001, .07]), and demand elasticity (B = .05, SE = .03, 95% CI [.006, .12]) significantly mediated the association between PTS symptoms and alcohol-related consequences. Craving remained a significant mediator in a multiple mediators model (B = .08, SE = .04, 95% CI [.03, .19]). Craving and alcohol demand may partially explain the relation between PTS status and alcohol-related consequences. Craving may be especially salient for individuals with PTS symptoms, as it may lead to more severe alcohol-related consequences even in the absence of elevated alcohol consumption. PMID:26375513

  15. Differential alcohol-related mortality among American Indian tribes in Oklahoma, 1968-1978.

    PubMed

    Christian, C M; Dufour, M; Bertolucci, D

    1989-01-01

    Tribal differences in alcohol-related mortality were examined among 11 Indian tribes living in Oklahoma. Data on alcohol-related deaths from 1968 to 1978 were compiled and assigned to various tribes on the basis of population distributions by county. Results showed significant differences in alcohol-related mortality among the various tribes. Of the 267,238 total deaths in Oklahoma during the study period, 9.3% of Indian deaths were alcohol-related while only 3.2% of those among blacks and 2.4% of those among whites were classified as such. Indian males and females are far more likely to die of alcohol-related deaths than their black and white counterparts. Cheyenne-Arapaho, Comanche and Kiowa areas (located in the western++ part of the state) have higher alcohol-related deaths than Cherokee, Choctaw, Creek, Seminole and Pawnee areas (located in eastern Oklahoma). Indian residents of the Seminole area have the lowest percentage of deaths identified as alcohol-related. The patterns which emerge may be due to different cultural and historical factors among the Indian tribes. PMID:2784011

  16. Genetic influences in emotional dysfunction and alcoholism-related brain damage

    PubMed Central

    Oscar-Berman, Marlene; Bowirrat, Abdalla

    2005-01-01

    Alcoholism is a complex, multifactorial disorder involving problematic ethanol ingestion; it results from the interplay between genetic and environmental factors. Personality, likewise, is formed from a combination of inherited and acquired influences. Because selected dimensions of emotional temperament are associated with distinct neurochemical substrates contributing to specific personality phenotypes, certain aspects of abnormal emotional traits in alcoholics may be inherited. Emotions involve complex subjective experiences engaging multiple brain regions, most notably the cortex, limbic system, and cerebellum. Results of in vivo magnetic resonance imaging and post-mortem neuropathological studies of alcoholics indicate that the greatest cortical loss occurs in the frontal lobes, with concurrent thinning of the corpus callosum. Additional damage has been documented for the amygdala and hippocampus, as well as in the white matter of the cerebellum. All of the critical areas of alcoholism-related brain damage are important for normal emotional functioning. When changes occur in these brain regions, either as a consequence of chronic ethanol abuse or from a genetic anomaly affecting temperament and/or a vulnerability to alcoholism, corresponding changes in emotional functions are to be expected. In alcoholics, such changes have been observed in their perception and evaluation of emotional facial expressions, interpretation of emotional intonations in vocal utterances, and appreciation of the meaning of emotional materials. PMID:18568071

  17. American Indian/Alaska Native Alcohol-Related Incarceration and Treatment

    PubMed Central

    Feldstein, Sarah W.; Venner, Kamilla L.; May, Philip A.

    2010-01-01

    American Indian/Alaska Natives have high rates of alcohol-related arrests and are overrepresented in justice systems. To understand the relationship between alcohol dependence, treatment, and alcohol-related incarceration, this study queried American Indian/Alaska Natives currently in remission from alcohol dependence. Participants reported receiving 0 to 43 treatment experiences. Moreover, participants had a significantly greater number of alcohol-related incarcerations than all other treatments combined. These findings underline the importance of making alcohol treatment available within criminal justice settings. PMID:17602406

  18. Measuring Functional Skills in Preschool Children at Risk for Neurodevelopmental Disabilities

    ERIC Educational Resources Information Center

    Msall, Michael E.

    2005-01-01

    Approximately 400,000 preschool children have a major neurodevelopmental disorder impacting on mobility, cognitive-adaptive, or communicative skills. As many as 1 in 3 children live at psychosocial disadvantage because of poverty, parental mental illness or substance misuse, or low parental educational (i.e. less than high school). In the past…

  19. Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities?

    PubMed Central

    Richardson, E.A.; Hill, S.E.; Mitchell, R.; Pearce, J.; Shortt, N.K.

    2015-01-01

    Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18–25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment. PMID:25840352

  20. Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities?

    PubMed

    Richardson, E A; Hill, S E; Mitchell, R; Pearce, J; Shortt, N K

    2015-05-01

    Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18-25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment. PMID:25840352

  1. Exploring College Students' Use of General and Alcohol-Related Social Media and Their Associations with Alcohol-Related Behaviors

    ERIC Educational Resources Information Center

    Hoffman, Eric W.; Pinkleton, Bruce E.; Weintraub Austin, Erica; Reyes-Velázquez, Wanda

    2014-01-01

    Objective: Alcohol marketers have increasingly moved their advertising efforts into digital and social media venues. As a result, the purpose of this study is to investigate associations between students' use of social media, their exposure to alcohol marketing messages through social media, and their alcohol-related beliefs and behaviors.…

  2. Brand preferences of underage drinkers who report alcohol-related fights and injuries

    PubMed Central

    Roberts, Sarah P.; Siegel, Michael B.; DeJong, William; Naimi, Timothy S.; Jernigan, David H.

    2014-01-01

    Background A significant body of research has demonstrated an association between adolescent alcohol consumption and subsequent fights and injuries. To date, however, no research has identified which brands are associated with alcohol-related fights and injuries among underage drinkers. Objectives We aimed to: 1) report the prevalence of alcohol-related fights and injuries among a national sample of underage drinkers in the U.S. and 2) describe the relationship between specific alcohol brand consumption and these alcohol-related negative consequences. Methods We recruited 1,031 self-reported drinkers (ages 13–20 years) via an internet panel maintained by Knowledge Networks to complete an online survey. Respondents reported their past-month overall and brand-specific alcohol consumption, risky drinking behavior, and past-year alcohol-related fights and injuries. Results Over one-quarter of the respondents (26.7%, N=232) reported at least one alcohol-related fight or injury in the past year. Heavy episodic drinkers were over six times more likely to report one of these negative alcohol-related consequences (AOR: 6.4, 95% CI: 4.1–9.9). Respondents of black race and those from higher-income households were also significantly more likely to report that experience (AOR: 2.2, 95% CI: 1.3–3.7; AOR: 1.8, 95% CI: 1.1–3.0 and 1.1–3.2, respectively). We identified eight alcohol brands that were significantly associated with alcohol-related fights and injuries. Conclusions/Importance Alcohol-related fights and injuries were frequently reported by adolescent respondents. Eight alcohol brands were significantly more popular among drinkers who experienced these adverse consequences. These results point to the need for further research on brand-specific correlates of underage drinking and negative health outcomes. PMID:25612075

  3. Alcohol-Related Visual Cues Impede the Ability to Process Auditory Information: Seeing but Not Hearing

    PubMed Central

    Monem, Ramey G.; Fillmore, Mark T.

    2015-01-01

    Studies of visual attention find that drinkers spend more time attending to images of alcohol-related stimuli compared to neutral images. It is believed that this attentional bias contributes to the maintenance of alcohol use. However, no research has examined the possibility that this bias of visual attention might actually impede the functioning of other modalities, such as the processing of accompanying auditory stimuli. This study aimed to determine if alcohol-related images engender greater sensory dominance than neutral images, such that processing accompanying information from another modality (audition) would be impeded. Drinkers who had an attentional bias to alcohol-related images performed a multisensory perception task that measured how alcohol-related versus neutral visual images affected their ability to detect and respond to simultaneously presented auditory signals. In accord with the hypothesis, compared with neutral images, the presentation of alcohol-related images impaired the ability to detect and respond to auditory signals. Increased dominance of the visual modality was demonstrated by more bimodal targets being misclassified as visual-only targets in the alcohol target condition compared with that of the neutral. Findings suggest that increased processing of alcohol-related stimuli may impede an individual’s ability to encode and interpret information obtained from other sensory modalities. PMID:26653149

  4. Reciprocal Effects of Internalizing and Oppositional Defiance Symptoms on Heavy Drinking and Alcohol-Related Harms in Young Adulthood

    PubMed Central

    Thompson, Kara D.; Leadbeater, Bonnie J.; Ames, Megan E.

    2015-01-01

    There is a need for longitudinal research to understand how psychopathology relates to the onset and maintenance of substance use from adolescence into young adulthood. Hence, we investigate the longitudinal, reciprocal influences of internalizing (anxiety and depression) and externalizing (oppositional defiance) symptoms on heavy episodic drinking (HED; ≥5 drinks per occasion) and alcohol-related harms in a community-based sample of youth aged 12–27 years. Participants were chosen from the Victoria Healthy Youth Survey, followed six times, biennially between 2003 and 2013 (N = 662). Analyses used cross-lagged panel models to examine reciprocal relations over time. Differences across age and sex were also tested. Defiance symptoms predicted increases in HED, which reciprocally predicted increases in defiance symptoms for females. Internalizing symptoms were related to HED within time for females. Alcohol-related harms had reciprocal positive associations with internalizing and defiance symptoms for both males and females. Associations were largely invariant across age groups, suggesting that the presence and strength of associations persisted across development. While psychopathology preceded the onset of HED and harms, the overall findings suggest that these risk processes are mutually reinforcing across development and that youth may become entrenched in an interdependent cycle that significantly increases their risk of comorbid disorders in adulthood. PMID:26819553

  5. Measuring illness insight in patients with alcohol-related cognitive dysfunction using the Q8 questionnaire: a validation study

    PubMed Central

    Walvoort, Serge JW; van der Heijden, Paul T; Kessels, Roy PC; Egger, Jos IM

    2016-01-01

    Aim Impaired illness insight may hamper treatment outcome in patients with alcohol-related cognitive deficits. In this study, a short questionnaire for the assessment of illness insight (eg, the Q8) was investigated in patients with Korsakoff’s syndrome (KS) and in alcohol use disorder (AUD) patients with mild neurocognitive deficits. Methods First, reliability coefficients were computed and internal structure was investigated. Then, comparisons were made between patients with KS and patients with AUD. Furthermore, correlations with the Dysexecutive Questionnaire (DEX) were investigated. Finally, Q8 total scores were correlated with neuropsychological tests for processing speed, memory, and executive function. Results Internal consistency of the Q8 was acceptable (ie, Cronbach’s α =0.73). The Q8 items represent one factor, and scores differ significantly between AUD and KS patients. The Q8 total score, related to the DEX discrepancy score and scores on neuropsychological tests as was hypothesized, indicates that a higher degree of illness insight is associated with a higher level of cognitive functioning. Conclusion The Q8 is a short, valid, and easy-to-administer questionnaire to reliably assess illness insight in patients with moderate-to-severe alcohol-related cognitive dysfunction. PMID:27445476

  6. Neurodevelopmental problems and extremes in BMI

    PubMed Central

    Tajnia, Armin; Lichtenstein, Paul; Lundström, Sebastian; Anckarsäter, Henrik; Nilsson, Thomas; Råstam, Maria

    2015-01-01

    Background. Over the last few decades, an increasing number of studies have suggested a connection between neurodevelopmental problems (NDPs) and body mass index (BMI). Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) both seem to carry an increased risk for developing extreme BMI. However, the results are inconsistent, and there have been only a few studies of the general population of children. Aims. We had three aims with the present study: (1) to define the prevalence of extreme (low or high) BMI in the group of children with ADHD and/or ASDs compared to the group of children without these NDPs; (2) to analyze whether extreme BMI is associated with the subdomains within the diagnostic categories of ADHD or ASD; and (3) to investigate the contribution of genetic and environmental factors to BMI in boys and girls at ages 9 and 12. Method. Parents of 9- or 12-year-old twins (n = 12,496) were interviewed using the Autism—Tics, ADHD and other Comorbidities (A-TAC) inventory as part of the Child and Adolescent Twin Study in Sweden (CATSS). Univariate and multivariate generalized estimated equation models were used to analyze associations between extremes in BMI and NDPs. Results. ADHD screen-positive cases followed BMI distributions similar to those of children without ADHD or ASD. Significant association was found between ADHD and BMI only among 12-year-old girls, where the inattention subdomain of ADHD was significantly associated with the high extreme BMI. ASD scores were associated with both the low and the high extremes of BMI. Compared to children without ADHD or ASD, the prevalence of ASD screen-positive cases was three times greater in the high extreme BMI group and double as much in the low extreme BMI group. Stereotyped and repetitive behaviors were significantly associated with high extreme BMIs. Conclusion. Children with ASD, with or without coexisting ADHD, are more prone to have low or high extreme BMIs than children

  7. The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.

    PubMed

    Bromley, R

    2016-09-01

    A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research. PMID:27312074

  8. Transketolase: observations in alcohol-related brain damage research.

    PubMed

    Alexander-Kaufman, Kimberley; Harper, Clive

    2009-04-01

    Thiamin, or vitamin B1, is crucial for brain function. In its active form, thiamin pyrophosphate (TPP), it is a co-enzyme for several enzymes, including transketolase. Transketolase is an important enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), a pathway responsible for generating reducing equivalents, which is essential for energy transduction and for generating ribose for nucleic acid synthesis. Transketolase also links the PPP to glycolysis, allowing a cell to adapt to a variety of energy needs, depending on its environment. Abnormal transketolase expression and/or activity have been implicated in a number of diseases where thiamin availability is low, including Wernicke-Korsakoff's Syndrome and alcoholism. Yet, the precise mechanism by which this enzyme is involved in the pathophysiology of these disorders remains controversial. PMID:18490188

  9. [Neurodevelopmental outcome of very premature infants].

    PubMed

    Bickle Graz, M; Newman, C J; Borradori-Tolsa, C

    2014-02-19

    Very preterm infants are at risk of neurodevelopmental impairments, which may affect motor development, intelligence and behavior. Neurodevelopmental follow-up is offered to these children who represent 1% of Swiss births, and may show abnormal motor tone, which sometimes resolves spontaneously or evolves in cerebral palsy. Standardized tests explore intellectual functioning and may allow the diagnosis of specific learning impediments. Finally, behavior is assessed with standardized questionnaires which can reveal hyperactivity with or without attention deficit, impaired social relations, psychiatric troubles or autism, all more frequent amongst preterm children. PMID:24640281

  10. Neurobehavioural and neurodevelopmental effects of pesticide exposures

    PubMed Central

    London, Leslie; Beseler, Cheryl; Bouchard, Maryse F.; Bellinger, David C.; Colosio, Claudio; Grandjean, Philippe; Harari, Raul; Kootbodien, Tahira; Kromhout, Hans; Little, Francesca; Meijster, Tim; Moretto, Angelo; Rohlman, Diane S.; Stallones, Lorann

    2012-01-01

    The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes amongst occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or pre-natal exposure. PMID:22269431

  11. Behavioral Interventions for Children and Adolescents With Fetal Alcohol Spectrum Disorders

    PubMed Central

    Paley, Blair; O’Connor, Mary J.

    2011-01-01

    Exposure to alcohol in utero is considered to be a leading cause of developmental disabilities of known causation. The most severe consequence of such exposure, fetal alcohol syndrome (FAS), is characterized by a distinct constellation of facial anomalies, growth retardation, and central nervous system dysfunction. Both animal and human studies, however, suggest that there may be considerable variability in the manifestations of in utero alcohol exposure across individuals, and, consequently, the term fetal alcohol spectrum disorders (FASD) has come into usage to reflect the entire continuum of effects associated with such exposure. In addition to FAS, this term encompasses the conditions of partial FAS, alcohol-related neurodevelopmental disorder, and alcohol-related birth defects. Despite extensive evidence of significant cognitive, behavioral, and social deficits in people with FASD, research on behavioral interventions for FASD has lagged behind. However, in recent years there has been a marked increase in efforts to design and test interventions for this population. This article will review current empirically tested interventions, methodological challenges, and suggestions for future directions in research on the treatment of FASD. PMID:23580043

  12. Integrative Review of Genetic Factors Influencing Neurodevelopmental Outcomes in Preterm Infants.

    PubMed

    Blair, Lisa M; Pickler, Rita H; Anderson, Cindy

    2016-03-01

    Preterm infants are at elevated risk for a host of neurodevelopmental problems, including disorders that appear later in life. Gene-environment interactions and prematurity may combine to increase the risk for poor neurodevelopmental outcomes. Increasing evidence supports a genetic link to risk for atypical development; however, no genomic risk profiles are currently used for infants without apparent genetic disorders. The purpose of this review was to synthesize recent evidence of genetic associations with atypical neurodevelopmental outcomes that may affect preterm infants who do not have a rare genetic disease. Electronic and hand-search strategies were used to find relevant articles that were English-language, peer-reviewed primary research or meta-analysis reports published between July 2009 and July 2014, involving human participants. Articles included in the analysis (N = 29) used a wide range of study designs and methodologies, complicating the analysis. An integrative-review design was used to synthesize the data. Numerous genes (n = 43) and additional large deletion copy number variants were associated with neurodevelopmental outcomes, including cognition, attention, perception, psychiatric disease, autism spectrum disorder, cerebral palsy, infant behavior, and alterations in brain architecture. The creation of genetic risk profiles for complex disorders of neurodevelopment is presently hindered by inconsistent genetic-association evidence, methodological considerations, reporting problems, and lack of replication. However, several avenues of investigation offer promise, including large (>100 kb) copy number variants and the candidate genes MET, NRG3, and SLC6A4, each of which were reported to have associations with neurodevelopmental outcomes in multiple, high-quality studies. PMID:26374169

  13. Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.

    PubMed

    Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2016-09-01

    Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4-by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. PMID:27413119

  14. An Experience Sampling Study of PTSD and Alcohol Related Problems

    PubMed Central

    Gaher, Raluca M.; Simons, Jeffrey S.; Hahn, Nicole L; Hofman, Jamie Hansen; Hofman, Jamie Hansen; Buchkoski, Jerome

    2014-01-01

    Posttraumatic stress disorder (PTSD) represents a debilitating psychiatric condition that is affecting the lives of many returning veterans. PTSD and alcohol use and dependence are highly comorbid. The purpose of this study was to understand the functional mechanisms between PTSD and alcohol use and problems. Specifically, the role of negative urgency and emotional intelligence were investigated as vulnerability and resiliency factors, respectively. This study utilized experience sampling to test associations between PTSD symptoms and alcohol use and related problems in a sample of 90 OIF/OEF veterans. Participants completed eight brief questionnaires daily for two weeks on palmtop computers. Elevations in PTSD symptoms during the day were associated with subsequent increases in alcohol use and associated problems that night. PTSD symptoms were associated with greater problems above and beyond the effect of drinking level at both the within- and between- person level. Emotional intelligence was associated with lower negative urgency, fewer PTSD symptoms, and less alcohol use and associated problems. The effects of emotional intelligence were primarily indirect via negative urgency and the effects of negative urgency on alcohol use and problems were indirect via its positive association with PTSD symptoms. Hypothesized cross-level effects of emotional intelligence and negative urgency were not supported. The findings suggest a functional association between PTSD symptoms and alcohol consumption. The association between PTSD symptoms and alcohol consumption is consistent with a self-medication model. However, the significant associations between PTSD symptoms and alcohol problems, after controlling for use level, suggest a broader role of dysregulation. PMID:25134021

  15. Inequalities in Alcohol-Related Mortality in 17 European Countries: A Retrospective Analysis of Mortality Registers

    PubMed Central

    Mackenbach, Johan P.; Kulhánová, Ivana; Bopp, Matthias; Borrell, Carme; Deboosere, Patrick; Kovács, Katalin; Looman, Caspar W. N.; Leinsalu, Mall; Mäkelä, Pia; Martikainen, Pekka; Menvielle, Gwenn; Rodríguez-Sanz, Maica; Rychtaříková, Jitka; de Gelder, Rianne

    2015-01-01

    Background Socioeconomic inequalities in alcohol-related mortality have been documented in several European countries, but it is unknown whether the magnitude of these inequalities differs between countries and whether these inequalities increase or decrease over time. Methods and Findings We collected and harmonized data on mortality from four alcohol-related causes (alcoholic psychosis, dependence, and abuse; alcoholic cardiomyopathy; alcoholic liver cirrhosis; and accidental poisoning by alcohol) by age, sex, education level, and occupational class in 20 European populations from 17 different countries, both for a recent period and for previous points in time, using data from mortality registers. Mortality was age-standardized using the European Standard Population, and measures for both relative and absolute inequality between low and high socioeconomic groups (as measured by educational level and occupational class) were calculated. Rates of alcohol-related mortality are higher in lower educational and occupational groups in all countries. Both relative and absolute inequalities are largest in Eastern Europe, and Finland and Denmark also have very large absolute inequalities in alcohol-related mortality. For example, for educational inequality among Finnish men, the relative index of inequality is 3.6 (95% CI 3.3–4.0) and the slope index of inequality is 112.5 (95% CI 106.2–118.8) deaths per 100,000 person-years. Over time, the relative inequality in alcohol-related mortality has increased in many countries, but the main change is a strong rise of absolute inequality in several countries in Eastern Europe (Hungary, Lithuania, Estonia) and Northern Europe (Finland, Denmark) because of a rapid rise in alcohol-related mortality in lower socioeconomic groups. In some of these countries, alcohol-related causes now account for 10% or more of the socioeconomic inequality in total mortality. Because our study relies on routinely collected underlying causes of

  16. Prediction of Neurodevelopmental Sequelae in VLBW Infants.

    ERIC Educational Resources Information Center

    Wolke, Dieter; And Others

    The study examined pre-, peri-, and neonatal factors in 271 British infants (weighing less than 1500 grams at birth), 188 of whom survived to 2 years. The study represented an attempt to define those factors which predict normal neurodevelopmental outcome in very low birth weight (VLBW) infants. Surviving infants were seen at 3, 6, 9, 12, and 24…

  17. Neurodevelopmental outcome of transient neonatal intracerebral echodensities.

    PubMed

    Appleton, R E; Lee, R E; Hey, E N

    1990-01-01

    The later neurodevelopmental progress of 15 babies who had neonatal periventricular echodensities or flares in the absence of any intraventricular bleeding or subsequent cystic degeneration was studied. At follow up four infants had neurological abnormalities, including spastic diplegia (n = 2). These findings suggest that transient flares may represent mild periventricular leucomalacia with consequent mild neurological dysfunction. PMID:2407199

  18. HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome

    PubMed Central

    Hollstein, Ronja; Parry, David A; Nalbach, Lisa; Logan, Clare V; Strom, Tim M; Hartill, Verity L; Carr, Ian M; Korenke, Georg C; Uppal, Sandeep; Ahmed, Mushtaq; Wieland, Thomas; Markham, Alexander F; Bennett, Christopher P; Gillessen-Kaesbach, Gabriele; Sheridan, Eamonn G; Kaiser, Frank J; Bonthron, David T

    2015-01-01

    Background The genetic aetiology of neurodevelopmental defects is extremely diverse, and the lack of distinctive phenotypic features means that genetic criteria are often required for accurate diagnostic classification. We aimed to identify the causative genetic lesions in two families in which eight affected individuals displayed variable learning disability, spasticity and abnormal gait. Methods Autosomal recessive inheritance was suggested by consanguinity in one family and by sibling recurrences with normal parents in the second. Autozygosity mapping and exome sequencing, respectively, were used to identify the causative gene. Results In both families, biallelic loss-of-function mutations in HACE1 were identified. HACE1 is an E3 ubiquitin ligase that regulates the activity of cellular GTPases, including Rac1 and members of the Rab family. In the consanguineous family, a homozygous mutation p.R219* predicted a truncated protein entirely lacking its catalytic domain. In the other family, compound heterozygosity for nonsense mutation p.R748* and a 20-nt insertion interrupting the catalytic homologous to the E6-AP carboxyl terminus (HECT) domain was present; western blot analysis of patient cells revealed an absence of detectable HACE1 protein. Conclusion HACE1 mutations underlie a new autosomal recessive neurodevelopmental disorder. Previous studies have implicated HACE1 as a tumour suppressor gene; however, since cancer predisposition was not observed either in homozygous or heterozygous mutation carriers, this concept may require re-evaluation. PMID:26424145

  19. Subjective Experience of Episodic Memory and Metacognition: A Neurodevelopmental Approach

    PubMed Central

    Souchay, Céline; Guillery-Girard, Bérengère; Pauly-Takacs, Katalin; Wojcik, Dominika Zofia; Eustache, Francis

    2013-01-01

    Episodic retrieval is characterized by the subjective experience of remembering. This experience enables the co-ordination of memory retrieval processes and can be acted on metacognitively. In successful retrieval, the feeling of remembering may be accompanied by recall of important contextual information. On the other hand, when people fail (or struggle) to retrieve information, other feelings, thoughts, and information may come to mind. In this review, we examine the subjective and metacognitive basis of episodic memory function from a neurodevelopmental perspective, looking at recollection paradigms (such as source memory, and the report of recollective experience) and metacognitive paradigms such as the feeling of knowing). We start by considering healthy development, and provide a brief review of the development of episodic memory, with a particular focus on the ability of children to report first-person experiences of remembering. We then consider neurodevelopmental disorders (NDDs) such as amnesia acquired in infancy, autism, Williams syndrome, Down syndrome, or 22q11.2 deletion syndrome. This review shows that different episodic processes develop at different rates, and that across a broad set of different NDDs there are various types of episodic memory impairment, each with possibly a different character. This literature is in agreement with the idea that episodic memory is a multifaceted process. PMID:24399944

  20. Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

    PubMed

    Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

    2015-03-01

    In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. PMID:25654988

  1. Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders.

    PubMed

    Hoyme, H Eugene; Kalberg, Wendy O; Elliott, Amy J; Blankenship, Jason; Buckley, David; Marais, Anna-Susan; Manning, Melanie A; Robinson, Luther K; Adam, Margaret P; Abdul-Rahman, Omar; Jewett, Tamison; Coles, Claire D; Chambers, Christina; Jones, Kenneth L; Adnams, Colleen M; Shah, Prachi E; Riley, Edward P; Charness, Michael E; Warren, Kenneth R; May, Philip A

    2016-08-01

    The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol. PMID:27464676

  2. Optic nerve hypoplasia, encephalopathy, and neurodevelopmental handicap.

    PubMed Central

    Burke, J P; O'Keefe, M; Bowell, R

    1991-01-01

    Abnormalities of the central nervous system are frequently described in optic nerve hypoplasia. In a longitudinal study of 46 consecutive children (32 term, 14 preterm) with bilateral optic nerve hypoplasia 32 (69.5%) had associated neurodevelopmental handicap. Of these, 90% had structural central nervous system abnormalities on computed tomographic brain scans. Neurodevelopmental handicap occurred in 62.5% of the term and 86% of the preterm infants respectively. Term infants had a greater incidence of ventral developmental midline defects and proportionately fewer maternal and/or neonatal complications throughout pregnancy, while encephaloclastic lesions were commoner among the premature infants. An association of optic nerve hypoplasia with the twin transfusion syndrome and prenatal vascular encephalopathies is described. PMID:2021594

  3. Protective Behavioral Strategies and Negative Alcohol-Related Consequences in College Students

    ERIC Educational Resources Information Center

    Araas, Teresa E.; Adams, Troy B.

    2009-01-01

    Objective: Alcohol abuse among college students is associated with a quality of life burden. The current study replicated and extended previous research on protective behavioral strategies (PBS) by examining relationships between PBS use and negative alcohol-related consequences. Method: A national sample of 29,792 U. S. college students who…

  4. An Employee Assistance Model of Health Care Management for Employees with Alcohol-Related Problems.

    ERIC Educational Resources Information Center

    Carson, Kerry D.; Balkin, David B.

    1992-01-01

    Describes employee assistance model in which cost-effective, high-quality treatment can be offered for a complex range of alcohol-related problems. Notes that this system of care allows the employee to be treated in the least restrictive therapeutic environment, thus encouraging continued productivity at work. (Author/NB)

  5. The origin of alcohol-related social norms in the Saami minority.

    PubMed

    Larsen, S

    1993-04-01

    The present paper addressed the problem of the origin of alcohol-related social norms in the Saami minority in northern Norway. Based on data from studies of comparable ethnic minorities in Greenland, North America and Australia it could be expected that alcohol use- and abuse would be more prevalent in the Saami than in the Norwegian populations of northern Norway. No data to support this hypothesis exist. On the contrary, available data suggest that drinking problems in this group are similar to those of the majority in the area. The present paper developed the hypothesis that Saami alcohol-related social norms originated in the Laestadian religious revival. The paper investigated the impact of the Laestadian culture in the formation of alcohol-related social norms. It was concluded that the Laestadian sobriety norm, and the norm of abstinence from the use of adiafora, have influenced alcohol-related behaviour in the Saami group in such a way that this group does not conform to the drinking behaviour found in comparable minorities. PMID:8485427

  6. The Effects of Sleep Problems and Depression on Alcohol-Related Negative Consequences among College Students

    ERIC Educational Resources Information Center

    Wattenmaker McGann, Amanda

    2013-01-01

    Previous literature provides an overview of the multiple relationships between alcohol use, protective behavioral strategies (PBS), alcohol-related negative consequences, depression, and sleep problems among college students, as well as differences by individual level characteristics, such as age, gender, and race/ethnicity. The purpose of this…

  7. Truancy, Alcohol Use and Alcohol-Related Problems in Secondary School Pupils in Norway

    ERIC Educational Resources Information Center

    Mounteney, J.; Haugland, S.; Skutle, A.

    2010-01-01

    This study focuses on a vulnerable group of pupils often missed by mainstream school surveys. It explores alcohol use and alcohol-related problems for a sample of truants of secondary school age, comparing behaviours with a school-based sample from the same geographical area. Analyses are based on a survey among truants (n = 107) and a school…

  8. The moderating role of implicit alcohol-related cognitions in hazardous alcohol use

    PubMed Central

    Cavanagh, Lucia; Obasi, Ezemenari M.

    2015-01-01

    The present study applied the Go/No-Go Association Test (GNAT; Nosek & Banaji, 2001) to measure alcohol-related implicit cognitions. Additionally, it assessed the role of implicit cognitions as a potential moderator in the relationship between explicit predictors of alcohol use and hazardous drinking behavior. University undergraduate students (N = 214) completed self-report questionnaires assessing reasons for drinking and reported alcohol use. Participants also completed two GNATs assessing implicit-alcohol-related cognitions associated with attitude (good-bad) and perceived safety (safe-dangerous). As expected, participants held implicit appraisals of alcohol as ‘‘bad’’ and ‘‘dangerous’’ in the context of nonalcoholic drinks, and as ‘‘good’’ and ‘‘safe’’ in the context of licit and illicit drugs. Implicit alcohol-related cognitions moderated the relationship between drinking to cope with negative affect and hazardous drinking and drinking due to cues or craving and hazardous drinking. These findings highlight the multidimensional nature of implicit cognitions and the role of negative implicit alcohol-related associations in moderating relationships between explicit processes and subsequent alcohol use behaviors. PMID:26989352

  9. An Examination of College Students' Receptiveness to Alcohol-Related Information and Advice

    ERIC Educational Resources Information Center

    Leahy, Matthew M.; Jouriles, Ernest N.; Walters, Scott T.

    2013-01-01

    This project examined the reliability and validity of a newly developed measure of college students' receptiveness to alcohol related information and advice. Participants were 116 college students who reported having consumed alcohol at some point in their lifetime. Participants completed a measure of receptiveness to alcohol-related…

  10. Positive and Negative Alcohol-Related Consequences: Associations with Past Drinking

    ERIC Educational Resources Information Center

    Lee, Christine M.; Maggs, Jennifer L.; Neighbors, Clayton; Patrick, Megan E.

    2011-01-01

    While recent attention suggests that positive and negative alcohol-related expectancies are important determinants of alcohol use, less is known about what types of consequences young people report actually experiencing when drinking alcohol. The present study (N = 742, 54% women) examined positive (Fun/Social, Relaxation/Coping, Positive Image)…

  11. Alcohol-Related Vehicular Death Rates for College Students in the Commonwealth of Virginia

    ERIC Educational Resources Information Center

    Turner, James; Bauerle, Jennifer; Keller, Adrienne

    2011-01-01

    Objective: Determine rate of college student alcohol-related vehicular traffic fatalities in Virginia during 2007. Participants: Undergraduates at colleges and universities in Virginia. Methods: Institutions with membership in the American College Health Association were invited to participate in a survey. Data collected from institutional reports…

  12. Binge Drinking and Alcohol-Related Problems among Community College Students: Implications for Prevention Policy

    ERIC Educational Resources Information Center

    Sheffield, Felicia D.; Darkes, Jack; Del Boca, Frances K.; Goldman, Mark S.

    2005-01-01

    Binge drinking and alcohol-related problems among students at traditional 4-year universities have been well documented. However, little is known about the frequency of their such behaviors and its consequences among community college students, who comprise roughly 44% of all undergraduate students in the United States. The present study examined…

  13. Perfectionism, Perceived Stress, Drinking to Cope, and Alcohol-Related Problems among College Students

    ERIC Educational Resources Information Center

    Rice, Kenneth G.; Van Arsdale, Amy C.

    2010-01-01

    This study investigated the association between perfectionism (categorized by adaptive perfectionistic, maladaptive perfectionistic, or nonperfectionistic groups), perceived stress, drinking alcohol to cope, and alcohol-related problems in a large sample of college students (N = 354). Maladaptive perfectionists reported significantly higher levels…

  14. Alcohol-Related Incident Guardianship and Undergraduate College Parties: Enhancing the Social Norms Marketing Approach

    ERIC Educational Resources Information Center

    Gilbertson, Troy A.

    2006-01-01

    This randomized experiment examines the effects of contextual information on undergraduate college student's levels of alcohol-related incident guardianship at college parties. The research is conceptualized using routine activities theory and the theory of planned behavior. The experiment examines attitudinal variations about heavy drinking…

  15. Social and Environmental Predictors of Alcohol-Related Legal Infractions in College Students

    ERIC Educational Resources Information Center

    Juth, Vanessa; Smyth, Joshua M.; Thompson, Kevin; Nodes, Jennifer

    2010-01-01

    Research on alcohol consumption among college students is often limited by self-reported outcomes and a narrow focus of predictor factors. This study examined both traditional risk factors for alcohol use as well as broader factors (e.g., weather, seasons) in predicting objective negative outcomes of alcohol use--alcohol-related legal infractions…

  16. A Duty of Care: Non-Drinkers and Alcohol Related Harm among an Australian University Sample

    ERIC Educational Resources Information Center

    Mikhailovich, Katja; George, Amanda; Rickwood, Debra; Parker, Rhian

    2011-01-01

    Studies documenting the harm associated with excessive drinking amongst university students are numerous. Fewer studies have explored the experience of non-drinkers in the university setting. In 2008, 826 students aged 18-29 years responded to an online survey aiming to investigate alcohol use and alcohol related harm at an Australian university.…

  17. Genderedness of Bar Drinking Culture and Alcohol-Related Harms: A Multi-Country Study

    ERIC Educational Resources Information Center

    Roberts, Sarah C. M.; Bond, Jason; Korcha, Rachael; Greenfield, Thomas K.

    2013-01-01

    This study explores whether associations between consuming alcohol in bars and alcohol-related harms are consistent across countries and whether country-level characteristics modify associations. We hypothesized that genderedness of bar drinking modifies associations, such that odds of harms associated with bar drinking increase more rapidly in…

  18. Motivating Learning Disabled Offenders with Alcohol-Related Problems: A Pilot Study.

    ERIC Educational Resources Information Center

    Mendel, Elizabeth; Hipkins, Jane

    2002-01-01

    A study aimed to apply motivational interviewing techniques in assisting seven individuals with mental retardation and alcohol-related problems through the stages of change. The group met for one hour over three sessions and staff training was provided. Results demonstrated increases in motivation, self-efficacy, and determination to change their…

  19. American Indian/Alaska Native Alcohol-Related Incarceration and Treatment

    ERIC Educational Resources Information Center

    Feldstein, Sarah W.; Venner, Kamilla L.; May, Philip A.

    2006-01-01

    American Indian/Alaska Natives have high rates of alcohol-related arrests and are overrepresented in justice systems. To understand the relationship between alcohol dependence, treatment, and alcoholrelated incarceration, this study queried American Indian/Alaska Natives currently in remission from alcohol dependence. Participants reported…

  20. Prevalence and Psychosocial Correlates of Alcohol-Related Sexual Assault among University Students

    ERIC Educational Resources Information Center

    Howard, Donna E.; Griffin, Melinda A.; Boekeloo, Bradley O.

    2008-01-01

    This study examined the psychosocial correlates of alcohol-related sexual assault. Undergraduate students (N = 551) were recruited to complete a web-based survey. The outcome was a composite of 2 items: "experienced an unwanted sexual advance" or "was the victim of sexual assault or date rape" as a result of another's alcohol use. The predictors…

  1. Hospitalizations for Students with an Alcohol-Related Sanction: Gender and Pregaming as Risk Factors

    ERIC Educational Resources Information Center

    Ahmed, Rimsha; Hustad, John T. P.; LaSalle, Linda; Borsari, Brian

    2014-01-01

    Objective: The purpose of this study is to investigate whether pregaming (ie, drinking prior to a social event) is a risk factor for hospitalization. Participants: Participants (N = 516) were undergraduate students with an alcohol-related sanction. Methods: Participants completed a survey about alcohol use, as well as behaviors and experiences,…

  2. Harnessing the Power of Perception: Reducing Alcohol-Related Harm among Rural Teenagers

    ERIC Educational Resources Information Center

    Hughes, Clarissa; Julian, Roberta; Richman, Matthew; Mason, Ron; Long, Gillian

    2008-01-01

    This paper outlines early findings from the Tasmanian-based Social Norms Analysis Project (SNAP). The Social Norms model is presented as a theoretically informed, evidence-based model for reducing alcohol-related harm in youthful populations by utilising the complex and often positive contributions peer groups make to adolescent health and…

  3. Alcohol-Related Emergency Department Visits Associated with Collegiate Football Games

    ERIC Educational Resources Information Center

    Shook, Janice; Hiestand, Brian C.

    2011-01-01

    Objective: In 2003, after several post-college football game riots, multiple strategies including strict enforcement of open container laws were instituted by the authors' city and university. The authors compared alcohol-related visits to the on-campus emergency department (ED) associated with home football games in 2002 and 2006, hypothesizing…

  4. ErbB4 in Laminated Brain Structures: A Neurodevelopmental Approach to Schizophrenia

    PubMed Central

    Perez-Garcia, Carlos G.

    2015-01-01

    The susceptibility genes for schizophrenia Neuregulin-1 (NRG1) and ErbB4 have critical functions during brain development and in the adult. Alterations in the ErbB4 signaling pathway cause a variety of neurodevelopmental defects including deficiencies in neuronal migration, synaptic plasticity, and myelination. I have used the ErbB4-/- HER4heart KO mice to study the neurodevelopmental insults associated to deficiencies in the NRG1-ErbB4 signaling pathway and their potential implication with brain disorders such as schizophrenia, a chronic psychiatric disease affecting 1% of the population worldwide. ErbB4 deletion results in an array of neurodevelopmental deficits that are consistent with a schizophrenic model. First, similar defects appear in multiple brain structures, from the cortex to the cerebellum. Second, these defects affect multiple aspects of brain development, from deficits in neuronal migration to impairments in excitatory/inhibitory systems, including reductions in brain volume, cortical and cerebellar heterotopias, alterations in number and distribution of specific subpopulations of interneurons, deficiencies in the astrocytic and oligodendrocytic lineages, and additional insults in major brain structures. This suggests that alterations in specific neurodevelopmental genes that play similar functions in multiple neuroanatomical structures might account for some of the symptomatology observed in schizophrenic patients, such as defects in cognition. ErbB4 mutation uncovers flaws in brain development that are compatible with a neurodevelopmental model of schizophrenia, and it establishes a comprehensive model to study the basis of the disorder before symptoms are detected in the adult. PMID:26733804

  5. Neurodevelopmental effects of fetal antiepileptic drug exposure.

    PubMed

    Velez-Ruiz, Naymee J; Meador, Kimford J

    2015-03-01

    Many studies investigating cognitive outcomes in children of women with epilepsy report an increased risk of mental impairment. Verbal scores on neuropsychometric measures may be selectively more involved. While a variety of factors contribute to the cognitive problems of children of women with epilepsy, antiepileptic drugs (AEDs) appear to play a major role. The mechanisms by which AEDs affect neurodevelopmental outcomes remain poorly defined. Animal models suggest that AED-induced apoptosis, altered neurotransmitter environment, and impaired synaptogenesis are some of the mechanisms responsible for cognitive and behavioral teratogenesis. AEDs that are known to induce apoptosis, such as valproate, appear to affect children's neurodevelopment in a more severe fashion. Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains, and these appear to persist at least until the age of 6. Some studies have shown neurodevelopmental deficiencies associated with the use of phenobarbital and possibly phenytoin. So far, most of the investigations available suggest that fetal exposures to lamotrigine or levetiracetam are safer with regard to cognition when compared with other AEDs. Studies on carbamazepine show contradictory results, but most information available suggests that major poor cognitive outcomes should not be attributed to this medication. Overall, children exposed to polytherapy prenatally appear to have worse cognitive and behavioral outcomes compared with children exposed to monotherapy, and with the unexposed. There is an increase risk of neurodevelopmental deficits when polytherapy involves the use of valproate versus other agents. PMID:25693658

  6. Neurodevelopmental Outcomes in Children With Hemifacial Microsomia

    PubMed Central

    Collett, Brent R.; Speltz, Matthew L.; Cloonan, Yona Keich; Leroux, Brian G.; Kelly, Judith P.; Werler, Martha M.

    2011-01-01

    Objective To determine whether preadolescent children with hemifacial microsomia (HFM) have higher risk of neurodevelopmental delays than unaffected control individuals. Design Case-control follow-up study of neurodevelopment in children with and without HFM. Setting Case individuals were originally recruited from 26 craniofacial centers across the United States and Canada, and controls were recruited through community pediatricians. Participants One hundred thirty-six children with HFM (cases) and 568 unaffected children (controls). Main Exposure History of HFM. Main Outcome Measures The Peabody Picture Vocabulary Test–Third Edition, the Beery-Buktenica Developmental Test of Visual Motor Integration–Fifth Edition, and the Academic Competence scales from the Child Behavior Checklist and the Teacher Report Form. Results Children with HFM scored lower than controls on all measures (effect size = −0.27 to −0.45; P < .001 to P = .008). Compared with controls, cases were 2 to 3 times as likely to score in the at-risk range. Relative to controls, outcomes were worse for male cases and those whose mothers were 25 years or younger at the time of their birth. Cases with HFM plus other malformations had poorer outcomes, as did cases with hearing, vision, or speech impairments. Conclusions This is the first study, to our knowledge, to show that children with HFM have poorer neurodevelopmental outcomes than unaffected children, but further study using more detailed assessments is indicated. Clinically, the findings suggest that early neurodevelopmental screening is warranted for all children with HFM. PMID:21300653

  7. Differential trajectories of alcohol-related behaviors across the first year of college by parenting profiles

    PubMed Central

    Abar, Caitlin C.; Turrisi, Robert J.; Mallett, Kimberly A.

    2015-01-01

    This study examined the extent to which profiles of perceived parenting are associated with trajectories of alcohol-related behaviors across the first year of college. Method Participants were surveyed five times from the summer prior to college to the fall of the second year. A total 285 college students were enrolled from the incoming classes of consecutive cohorts of students at a large, public university in the Northeastern U.S. At baseline, participants provided information on their parents’ alcohol-related behaviors (e.g., parental modeling of use; perceived approval of underage use) and parenting characteristics (e.g., parental monitoring; parent-child relationship quality). Students also reported on their personal alcohol-related behaviors at each time point. Results Latent profile analysis was used to identify four subgroups based on the set of parenting characteristics: High Quality (14%) – highest parent-teen relationship quality; High Monitoring (31%) – highest parental monitoring and knowledge; Low Involvement (30%) – poor relationship quality, little monitoring and communication; and Pro-Alcohol (21%) – highest parental modeling and approval. Students were then assigned to profiles, and their alcohol-related behaviors were examined longitudinally using latent growth curve modeling. In general, students in the Pro-Alcohol profile displayed the highest baseline levels of typical weekend drinking, heavy episodic drinking, and peak BAC, in addition to showing steeper increases in typical weekend drinking across the first year of college. Discussion Results support the notion that parental behaviors remain relevant across the first year of college. Differential alcohol-related behaviors across parenting profiles highlight the potential for tailored college intervention. PMID:23915366

  8. Autism and related disorders.

    PubMed

    McPartland, James; Volkmar, Fred R

    2012-01-01

    The pervasive developmental disorders are a group of neurodevelopmental disorders that include autistic disorder, Asperger's disorder, pervasive developmental disorder - not otherwise specified (PDD-NOS), childhood disintegrative disorder (CDD), and Rett's disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (autistic disorder, Asperger's disorder, and PDD-NOS) are currently referred to as autism spectrum disorders, reflecting divergent phenotypic and etiological characteristics compared to Rett's disorder and CDD. This chapter reviews research and clinical information to appropriate medical diagnosis and treatment. PMID:22608634

  9. Autism and Related Disorders

    PubMed Central

    McPartland, James; Volkmar, Fred R.

    2012-01-01

    The Pervasive Developmental Disorders are a group of neurodevelopmental disorders that include Autistic Disorder, Asperger’s Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Childhood Disintegrative Disorder (CDD), and Rett’s Disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (Autistic Disorder, Asperger’s Disorder, and PDD-NOS) are currently referred to as Autism Spectrum Disorders, reflecting divergent phenotypic and etiologic characteristics compared to Rett’s Disorder and CDD. This chapter reviews relevant research and clinical information relevant to appropriate medical diagnosis and treatment. PMID:22608634

  10. Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes

    PubMed Central

    Oksenberg, N; Haliburton, G D E; Eckalbar, W L; Oren, I; Nishizaki, S; Murphy, K; Pollard, K S; Birnbaum, R Y; Ahituv, N

    2014-01-01

    The autism susceptibility candidate 2 gene (AUTS2) has been associated with multiple neurological diseases including autism spectrum disorders (ASDs). Previous studies showed that AUTS2 has an important neurodevelopmental function and is a suspected master regulator of genes implicated in ASD-related pathways. However, the regulatory role and targets of Auts2 are not well known. Here, by using ChIP-seq (chromatin immunoprecipitation followed by deep sequencing) and RNA-seq on mouse embryonic day 16.5 forebrains, we elucidated the gene regulatory networks of Auts2. We find that the majority of promoters bound by Auts2 belong to genes highly expressed in the developing forebrain, suggesting that Auts2 is involved in transcriptional activation. Auts2 non-promoter-bound regions significantly overlap developing brain-associated enhancer marks and are located near genes involved in neurodevelopment. Auts2-marked sequences are enriched for binding site motifs of neurodevelopmental transcription factors, including Pitx3 and TCF3. In addition, we characterized two functional brain enhancers marked by Auts2 near NRXN1 and ATP2B2, both ASD-implicated genes. Our results implicate Auts2 as an active regulator of important neurodevelopmental genes and pathways and identify novel genomic regions that could be associated with ASD and other neurodevelopmental diseases. PMID:25180570

  11. Alcohol-Related Problems in High-Risk Groups. EURO Reports and Studies 109. Report on a WHO Study.

    ERIC Educational Resources Information Center

    Plant, Martin, Ed.

    Alcohol consumption has risen dramatically in many countries since the Second World War. Accompanying this rise has been a rise in alcohol-related problems, including liver cirrhosis mortality, alcohol dependence, and alcohol-related crimes and accidents. Alcohol misuse presents huge health, social, and legal problems throughout most of Europe and…

  12. Alcohol-Related Problems and Risk of Suicide among College Students: The Mediating Roles of Belongingness and Burdensomeness

    ERIC Educational Resources Information Center

    Lamis, Dorian A.; Malone, Patrick S.

    2011-01-01

    The relationship among alcohol-related problems, perceived burdensomeness, thwarted belongingness, and suicide proneness in undergraduate college students (N = 996) was examined. As hypothesized, alcohol-related problems, perceived burdensomeness, and thwarted belongingness were all significantly and positively correlated with suicide proneness.…

  13. Neurodevelopmental Theories of Schizophernia : Application to Late-Onset Schizophernia

    PubMed Central

    Palmer, Barton W.; Jeste, Dilip V.

    1996-01-01

    A review of literature on the neurodevelopmental origins of schizophemia is presented, with particular attention to neurodevelopmental processes in late-onset schizophemia. Definitions of the term “neurodevelopmental” as used in schizophernia literature are first provided. Next, evidence for the developmental origins of the neuropathology in schizophemia is reviewed. This evidence includes studies of the associations between schizophemia and neurodevelopmental brain aberrations, minor physical anomalies, obstetric complications, prenatal viral exposure, childhood neuromotor abnormalities, and pandysmaturation. A brief discussion of the predominant theories about the neurodevelopmental origins of schizophemia is then provided. The concept and nature of “late-onset schizophenia ”is next defined and discussed. Finally, the neurodevelopmental literature is discussed in relation to the phenomenon of late-onset schizophemia. Based on this review, we conclude that there exists a strong likelihood that late-onset schizophrenia involves neurodevelopmental processes. PMID:21584112

  14. Opportunities for prevention of alcohol-related death in primary care: results from a population-based cross-sectional study.

    PubMed

    Morris, Margaret; Johnson, David; Morrison, David S

    2012-11-01

    The mortality rate from alcohol-related conditions has risen sharply in the United Kingdom and it is not known whether opportunities for preventive interventions could be improved. The purpose of our study was to identify opportunities to detect, assess, and manage alcohol problems in primary care according to evidence-based guidelines. We carried out a cross-sectional study on patients who died from alcohol-related conditions in the calendar year 2003 within National Health Service Greater Glasgow Health Board area, Scotland (population 920,000). We described patient characteristics and care recorded in health service records, comparing it with best evidence-based practice in Scottish Intercollegiate Guidelines Network and Health Technology Board for Scotland recommendations on the management of harmful drinking and alcohol dependence. 501 deaths occurred from an alcohol-related cause. The mean age at death was 57.5 years and 72% were male. The most common causes of death, recorded by the International Classification of Diseases, revision 10, excluding accidents, were alcoholic liver disease (290, 57.9%) and mental and behavioural disorders due to alcohol (70, 14.0%). Lifetime mean consultations at primary care general practitioner and hospital outpatient departments were 24 in males and 5 in females. All individuals who died from an alcohol-related cause had at least one biochemical or physical indicator suggestive of alcohol misuse. 21% (95% CI 13-33%) had no record of having been advised to abstain from alcohol and 23% (95% CI 15-35%) had received brief interventions. 58% (95% CI 46-70%) had been referred to specialist alcohol services but a third of them did not attend. The majority of patients (83%, 95% CI 72-90%) had no evidence of shared health service and social work care. We concluded that individuals who died from alcohol-related conditions were usually in contact with statutory and voluntary services but further efforts were required to use these

  15. The role of medical schools in the prevention of alcohol-related problems.

    PubMed Central

    Negrete, J C

    1990-01-01

    There is agreement that physicians can play a major role in the prevention of alcohol problems among their patients and that medical schools should prepare physicians for this role by teaching three major subject areas: knowledge, attitudes and clinical skills. Despite this agreement and the acknowledged high prevalence of alcohol problems in clinical populations, medical school coverage of these problems is not proportional to their importance. Barriers to adequate coverage of alcohol problems are traditional attitudes, confusion as to whether such problems are "medical" and lack of adequate faculty role models. These problems could be remedied by encouragement and training of interested faculty members, establishment of substance abuse centres in university medical schools, integration of alcohol-related material with relevant topics in all departments and inclusion of alcohol-related questions on medical qualifying exams. PMID:2224672

  16. Neurodevelopmental outcome after neonatal extracorporeal membrane oxygenation.

    PubMed Central

    Robertson, C M; Finer, N N; Sauve, R S; Whitfield, M F; Belgaumkar, T K; Synnes, A R; Grace, M G

    1995-01-01

    OBJECTIVE: To determine the neurodevelopmental outcome of neonates who underwent extracorporeal membrane oxygenation (ECMO group) and similarly critically ill newborns with a lower Oxygenation Index who underwent conventional treatment (comparison group), and to determine whether factors such as the underlying diagnosis and the distance transported from outlying areas affect outcome. DESIGN: Multicentre prospective longitudinal comparative outcome study. SETTING: An ECMO centre providing services to all of western Canada and four tertiary care neonatal follow-up clinics. SUBJECTS: All neonates who received treatment between February 1989 and January 1992 at the Western Canadian Regional ECMO Center and who were alive at 2 years of age; 38 (95%) of the 40 surviving ECMO-treated subjects and 26 (87%) of the 30 surviving comparison subjects were available for follow-up. INTERVENTIONS: ECMO or conventional therapy for respiratory failure. OUTCOME MEASURES: Neurodevelopmental disability (one or more of cerebral palsy, visual or hearing loss, seizures, severe cognitive disability), and mental and performance developmental indexes of the Bayley Scales of Infant Development. RESULTS: Six (16%) of the ECMO-treated children had neurodevelopmental disabilities at 2 years of age, as compared with 1 (4%) of the comparison subjects; the difference was not statistically significant. The mean mental developmental index (91.8 [standard deviation (SD) 19.5] v. 100.5 [SD 25.4]) and the mean performance developmental index (87.2 [SD 20.0] v. 96.4 [SD 20.9]) did not differ significantly between the ECMO group and the comparison group respectively. Among the ECMO-treated subjects those whose underlying diagnosis was sepsis had the lowest Bayley indexes, significantly lower than those whose underlying diagnosis was meconium aspiration syndrome. The distance transported did not affect outcome. CONCLUSIONS: Neurodevelopmental disability and delay occurred in both groups. The underlying

  17. Drinking, Driving, and Crashing: A Traffic-Flow Model of Alcohol-Related Motor Vehicle Accidents*

    PubMed Central

    Gruenewald, Paul J.; Johnson, Fred W.

    2010-01-01

    Objective: This study examined the influence of on-premise alcohol-outlet densities and of drinking-driver densities on rates of alcohol-related motor vehicle crashes. A traffic-flow model is developed to represent geographic relationships between residential locations of drinking drivers, alcohol outlets, and alcohol-related motor vehicle crashes. Method: Cross-sectional and time-series cross-sectional spatial analyses were performed using data collected from 144 geographic units over 4 years. Data were obtained from archival and survey sources in six communities. Archival data were obtained within community areas and measured activities of either the resident population or persons visiting these communities. These data included local and highway traffic flow, locations of alcohol outlets, population density, network density of the local roadway system, and single-vehicle nighttime (SVN) crashes. Telephone-survey data obtained from residents of the communities were used to estimate the size of the resident drinking and driving population. Results: Cross-sectional analyses showed that effects relating on-premise densities to alcohol-related crashes were moderated by highway traffic flow. Depending on levels of highway traffic flow, 10% greater densities were related to 0% to 150% greater rates of SVN crashes. Time-series cross-sectional analyses showed that changes in the population pool of drinking drivers and on-premise densities interacted to increase SVN crash rates. Conclusions: A simple traffic-flow model can assess the effects of on-premise alcohol-outlet densities and of drinking-driver densities as they vary across communities to produce alcohol-related crashes. Analyses based on these models can usefully guide policy decisions on the siting of on-premise alcohol outlets. PMID:20230721

  18. Alcohol-related cues potentiate alcohol impairment of behavioral control in drinkers.

    PubMed

    Weafer, Jessica; Fillmore, Mark T

    2015-06-01

    The acute impairing effects of alcohol on inhibitory control are well-established, and these disinhibiting effects are thought to play a role in its abuse potential. Alcohol impairment of inhibitory control is typically assessed in the context of arbitrary cues, yet drinking environments are comprised of an array of alcohol-related cues that are thought to influence drinking behavior. Recent evidence suggests that alcohol-related stimuli reduce behavioral control in sober drinkers, suggesting that alcohol impairment of inhibitory control might be potentiated in the context of alcohol cues. The current study tested this hypothesis by examining performance on the attentional-bias behavioral activation (ABBA) task that measures the degree to which alcohol-related stimuli can reduce inhibition of inappropriate responses in a between-subjects design. Social drinkers (N = 40) performed the task in a sober condition, and then again following placebo (0.0 g/kg) and a moderate dose of alcohol (0.65 g/kg) in counterbalanced order. Inhibitory failures were greater following alcohol images compared to neutral images in sober drinkers, replicating previous findings with the ABBA task. Moreover, alcohol-related cues exacerbated alcohol impairment of inhibitory control as evidenced by more pronounced alcohol-induced disinhibition following alcohol cues compared to neutral cues. Finally, regression analyses showed that greater alcohol-induced disinhibition following alcohol cues predicted greater self-reported alcohol consumption. These findings have important implications regarding factors contributing to binge or "loss of control" drinking. That is, the additive effect of disrupted control mechanisms via both alcohol cues and the pharmacological effects of the drug could compromise an individual's control over ongoing alcohol consumption. (PsycINFO Database Record PMID:25134023

  19. Prevalence of alcohol-related pathologies at autopsy: Estonian Forensic Study of Alcohol and Premature Death

    PubMed Central

    Tuusov, Jana; Lang, Katrin; Väli, Marika; Pärna, Kersti; Tõnisson, Mailis; Ringmets, Inge; McKee, Martin; Helander, Anders; Leon, David A

    2014-01-01

    Aims Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. Design, Setting and Participants Cross-sectional study included 554 men aged 25–54 in Estonia undergoing forensic autopsy in 2008–09. Measurements Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. Findings Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3–64.6] followed by the lungs (18.6%, 95% CI = 15.4–22.1), stomach (17.5%, 95% CI = 14.4–20.9), pancreas (14.1%, 95% CI = 11.3–17.3), heart (4.9%, 95% CI = 3.2–7.0) and oesophagus (1.4%, 95% CI = 0.6–2.8). Only a minority with liver pathology had a second pathology. The number of pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma-glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine). Despite the high prevalence of liver pathology, few deaths had alcoholic liver disease specified as the underlying cause. Conclusion The majority of 554 men aged 25–54 undergoing forensic autopsy in Estonia in 2008–09 showed evidence of alcohol-related pathology. However, the recording of deaths by underlying cause failed to capture the scale and nature of alcohol-induced pathologies found. PMID:25066373

  20. A Comparison of Victim, Offender, and Event Characteristics of Alcohol- and Non-Alcohol-Related Homicides

    PubMed Central

    Pridemore, William Alex; Eckhardt, Krista

    2009-01-01

    The authors used narrative data from court and police records of homicides in Russia to compare alcohol- and non-alcohol-related incidents on victim, offender, and event characteristics. Binary logistic regression models were estimated for neither participant drinking, offender drinking, victim drinking, and both drinking. Consistent differences were found between alcohol- and non-alcohol-related homicides across the models. Alcohol-related homicides were significantly more likely to occur overnight, to occur on weekends, and to result from acute arguments and significantly less likely to occur between strangers, to be profit motivated or premeditated, and to be carried out to hide other crimes. No significant differences between the drinking and nondrinking samples were found for victim’s gender, primary weapon used, or event location. The authors place these findings into the literature on the situational context of crime and create a tentative typology of homicide events, grounded in the results of their inductive approach, based on alcohol use by homicide offenders and victims. PMID:19802358

  1. Alcohol use and prior alcohol-related convictions as predictors of probation officer perceptions and sentencing.

    PubMed

    Harrell, W A

    1980-11-01

    Presentence reports for 740 offenders were content analyzed. Regression techniques were used to evaluate a number of predictors of sentencing, including the effects of number of prior alcohol-related convictions and whether the offender was intoxicated while committing the offense he was charged with. The two most prominent variables affecting the severity of sentence were the probation officer's assessment of the offender's probable success on probation and the legal seriousness of the offense. While failing to have any significant direct effects on sentencing, our measures of alcohol use had significant indirect effects which were mediated by the probation officer's assessment of success on probation and legal seriousness. An extensive criminal record of prior alcohol-related convictions resulted in a poorer prognosis for success on probation this, in turn, led to more severe sentences for these offenders. Intoxication while committing an offense was related to the commission of minor crimes which, subsequently, yielded more lenient treatment for alcohol-users compared to nonusers. Finally, native offenders were more likely than nonnatives to have many prior alcohol-related convictions and to have been intoxicated while committing an offense. PMID:7216566

  2. Alcohol-related expectancies in adults and adolescents: Similarities and disparities.

    PubMed

    Monk, Rebecca L; Heim, Derek

    2016-01-01

    This study aimed to contrast student and not student outcome expectancies, and explore the diversity of alcohol-related cognitions within a wider student sample. Participants (n=549) were college students (higher education-typically aged 15-18 years), university students (further education-typically aged 18-22 years) and business people (white collar professionals <50 years) who completed questionnaires in their place of work or education. Overall positive expectancies were higher in the college students than in the business or university samples. However, not all expectancy subcategories followed this pattern. Participant groups of similar age were therefore alike in some aspects of their alcohol-related cognitions but different in others. Similarly, participant groups whom are divergent in age appeared to be alike in some of their alcohol-related cognitions, such as tension reduction expectancies. Research often homogenises students as a specific sub-set of the population, this paper hi-lights that this may be an over-simplification. Furthermore, the largely exclusive focus on student groups within research in this area may also be an oversight, given the diversity of the findings demonstrated between these groups. PMID:26990388

  3. Drinking motives as moderators of the effect of ambivalence on drinking and alcohol-related problems

    PubMed Central

    Foster, Dawn W.; Neighbors, Clayton; Prokhorov, Alexander

    2014-01-01

    The current study seeks to evaluate relationships between drinking motives and alcohol-related ambivalence in the prediction of problem drinking. We expected that: 1) main effects would emerge such that alcohol-related ambivalence would be positively associated with peak drinking and problems; drinking motives would be positively associated with drinking and problems, and 2) interactions would emerge between motives and ambivalence in predicting problematic drinking such that drinking motives would be positively associated with peak drinking and problems, especially among those high in ambivalence over drinking. Six hundred sixty-nine undergraduate students (mean age = 22.95, SD = 5.47, 82.22% female) completed study materials. Results showed that consistent with expectations, ambivalence was positively associated with peak drinking and problems. Further, consistent with expectations, drinking motives were positively associated with peak drinking and problems. Additionally, ambivalence was positively associated with drinking motives. Significant interactions emerged between drinking motives (social and coping) and ambivalence when predicting peak drinking and alcohol-related problems. These findings highlight the importance of considering motives in the relationship between ambivalence and drinking. Clinical implications include the need for tailoring interventions to target individual difference factors that increase risk for heavy drinking and associated problems. This is especially important among college students who may be at risk for problematic behavior. PMID:24094922

  4. Drinking norms and alcohol-related problems in the United States.

    PubMed

    Linsky, A S; Colby, J P; Straus, M A

    1986-09-01

    One of Bales's three related hypotheses concerning how cultures or social structures influence the level of alcoholism in a population--that culturally determined attitudes toward drinking and intoxication determine whether alcohol will be used to relieve the stress generated in a society--is examined in the first systematic test of that hypothesis based on American data. A proscriptive norm index was computed for each of the 50 states based on percentage population residing in legally dry areas, the degree of legal restrictions on the sale or consumption of alcoholic beverages and the percentage population of Mormons and Fundamentalists. The most proscriptive states are located in the southern region of the United States. Proscriptive norms are significantly correlated with all of the indicators of alcohol-related problems studied. Most of the correlations remain significant when five other variables are controlled. Proscriptive norms are negatively correlated with the indicators of heavy drinking, but positively correlated with the "social disruptiveness" of alcohol (arrest data). Thus driving while intoxicated and other alcohol-related arrests do not appear to arise as a response to the total amount of drinking. Instead, such alcohol-related problems appear to be a response to the strong cultural disapproval of drinking, with the proscriptively oriented states experiencing the highest rates of disruptive behaviors related to alcohol. The findings are consistent with a social control explanation for this link. PMID:3762162

  5. Valproate-induced neurodevelopmental deficits in Xenopus laevis tadpoles.

    PubMed

    James, Eric J; Gu, Jenny; Ramirez-Vizcarrondo, Carolina M; Hasan, Mashfiq; Truszkowski, Torrey L S; Tan, Yuqi; Oupravanh, Phouangmaly M; Khakhalin, Arseny S; Aizenman, Carlos D

    2015-02-18

    Autism spectrum disorder (ASD) is increasingly thought to result from low-level deficits in synaptic development and neural circuit formation that cascade into more complex cognitive symptoms. However, the link between synaptic dysfunction and behavior is not well understood. By comparing the effects of abnormal circuit formation and behavioral outcomes across different species, it should be possible to pinpoint the conserved fundamental processes that result in disease. Here we use a novel model for neurodevelopmental disorders in which we expose Xenopus laevis tadpoles to valproic acid (VPA) during a critical time point in brain development at which neurogenesis and neural circuit formation required for sensory processing are occurring. VPA is a commonly prescribed antiepileptic drug with known teratogenic effects. In utero exposure to VPA in humans or rodents results in a higher incidence of ASD or ASD-like behavior later in life. We find that tadpoles exposed to VPA have abnormal sensorimotor and schooling behavior that is accompanied by hyperconnected neural networks in the optic tectum, increased excitatory and inhibitory synaptic drive, elevated levels of spontaneous synaptic activity, and decreased neuronal intrinsic excitability. Consistent with these findings, VPA-treated tadpoles also have increased seizure susceptibility and decreased acoustic startle habituation. These findings indicate that the effects of VPA are remarkably conserved across vertebrate species and that changes in neural circuitry resulting from abnormal developmental pruning can cascade into higher-level behavioral deficits. PMID:25698756

  6. Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

    PubMed

    Li, Qi; Chan, Siu Yuen; Wong, Kwun K; Wei, Ran; Leung, Yu On; Ding, Abby Y; Hui, Tomy C K; Cheung, Charlton; Chua, Siew E; Sham, Pak C; Wu, Ed X; McAlonan, Grainne M

    2016-07-01

    Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. PMID:26826030

  7. Expression of Human Gaucher Disease Gene GBA Generates Neurodevelopmental Defects and ER Stress in Drosophila Eye

    PubMed Central

    Ito, Kumpei; Hanai, Shuji; Aizawa, Hidenobu; Kato, Tomoki; Kawasaki, Kazunori; Yamaguchi, Terumi; Ryoo, Hyung Don; Goto-Inoue, Naoko; Setou, Mitsutoshi; Tsuji, Shoji; Ishida, Norio

    2013-01-01

    Gaucher disease (GD) is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase (GlcCerase). The accumulation of its substrate, glucocylceramide (GlcCer) is considered the main cause of GD. We found here that the expression of human mutated GlcCerase gene (hGBA) that is associated with neuronopathy in GD patients causes neurodevelopmental defects in Drosophila eyes. The data indicate that endoplasmic reticulum (ER) stress was elevated in Drosophila eye carrying mutated hGBAs by using of the ER stress markers dXBP1 and dBiP. We also found that Ambroxol, a potential pharmacological chaperone for mutated hGBAs, can alleviate the neuronopathic phenotype through reducing ER stress. We demonstrate a novel mechanism of neurodevelopmental defects mediated by ER stress through expression of mutants of human GBA gene in the eye of Drosophila. PMID:23936319

  8. Sex Differences and Neurodevelopmental Variables: A Vector Model

    ERIC Educational Resources Information Center

    Languis, Marlin; Naour, Paul

    For the individual, gender difference falls along the feminine-masculine continuum with strong neurodevelopmental influences at various points throughout the lifespan. Neurodevelopmental influences are conceptualized in a vector model of sex difference. Vector attributes, direction and magnitude, are influenced initially by differences in levels…

  9. Screening for Fetal Alcohol Spectrum Disorders by Nonmedical Community Workers

    PubMed Central

    O’Connor, Mary J.; Rotheram-Borus, Mary Jane; Tomlinson, Mark; Bill, Claudine; LeRoux, Ingrid M.; Stewart, Jackie

    2015-01-01

    Background South Africa has the highest prevalence of Fetal Alcohol Spectrum Disorders (FASD) in the world yet many women have no access to clinic care or to physicians in their communities. The shortage of physicians trained in the diagnosis of FASD is even more severe. Thus there is a need to train community workers to assist in the delivery of health care. Objectives This study reports on the effectiveness of training community workers to screen for a possible diagnosis of a FASD. Methods Community workers in Cape Town, South Africa were trained to screen for FASD in 139, 18-month-old toddlers with prenatal alcohol exposure (PAE). Children were assessed according to the salient characteristics of individuals with PAE using height, weight, head circumference (OFC), philtrum, and lip measurements according to criteria set forth by the Institute of Medicine. Screen-positive children were referred for diagnostic assessment to a pediatrician reliably trained in the diagnosis of FASD. Results Of the screen-positive children, 93% received an FASD diagnosis suggesting that the screening procedure was highly sensitive. Diagnoses included 15% with fetal alcohol syndrome (FAS), 23% with Partial FAS, and 62% with Alcohol Related Neurodevelopmental Disorder (ARND, provisional). Conclusion The use of community workers to screen for FASD represents a promising approach to effective diagnosis of children affected by PAE in areas lacking adequate medical resources. PMID:25658901

  10. Neuroimaging of the Philadelphia Neurodevelopmental Cohort

    PubMed Central

    Satterthwaite, Theodore D.; Elliott, Mark A.; Ruparel, Kosha; Loughead, James; Prabhakaran, Karthik; Calkins, Monica E.; Hopson, Ryan; Jackson, Chad; Keefe, Jack; Riley, Marisa; Mensh, Frank D.; Sleiman, Patrick; Verma, Ragini; Davatzikos, Christos; Hakonarson, Hakon; Gur, Ruben C.; Gur, Raquel E.

    2013-01-01

    The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1,445 adolescents ages 8–21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development. PMID:23921101

  11. Social Inequalities and Gender Differences in the Experience of Alcohol-Related Problems

    PubMed Central

    Grittner, Ulrike; Kuntsche, Sandra; Graham, Kathryn; Bloomfield, Kim

    2012-01-01

    Aims: To examine the influence of country-level characteristics and individual socio-economic status (SES) on individual alcohol-related consequences. Methods: Data from 42,655 men and women collected by cross-sectional surveys in 25 countries of the Gender, Alcohol and Culture: An International Study study were used. The individual SES was measured by the highest attained educational level. Alcohol-related consequences were defined as the self-report of at least one internal or one external consequence in the last year. The relationship between individuals’ education and alcohol-related consequences was examined by meta-analysis. In a second step, the individual level data and country data were combined in multilevel models. As country-level indicators, we used the purchasing power parity of the gross national income (GNI), the Gini coefficient and the Gender Gap Index. Results: Lower educated men and women were more likely to report consequences than higher educated men and women even after controlling for drinking patterns. For men, this relation was significant for both internal and external problems. For women, it was only significant for external problems. The GNI was significantly associated with reporting external consequences for men such that in lower income countries men were more likely to report social problems. Conclusion: The fact that problems accrue more quickly for lower educated persons even if they drink in the same manner can be linked to the social or environmental dimension surrounding problems. That is, those of fewer resources are less protected from the experience of a problem or the impact of a stressful life event. PMID:22542707

  12. Help-seeking for alcohol-related problems in college students: correlates and preferred resources.

    PubMed

    Buscemi, Joanna; Murphy, James G; Martens, Matthew P; McDevitt-Murphy, Meghan E; Dennhardt, Ashley A; Skidmore, Jessica R

    2010-12-01

    Despite the development of a variety of efficacious alcohol intervention approaches for college students, few student drinkers seek help. The present study assessed students' history of help-seeking for alcohol problems, as well as their estimates of how likely they would be to use various help-seeking resources, should they wish to change their drinking. Participants were 197 college students who reported recent heavy drinking (46% male, 68.5% White, 27.4% African-American). Participants completed measures related to their drinking and their use (both past use and likelihood of future use) of 14 different alcohol help-seeking options. Repeated-measures analyses of variance revealed that students preferred informal help-seeking (e.g., talking to friends and family) over formal (e.g., talking with a counselor or medical provider) and anonymous resources (e.g., internet- or computer-based programs). Higher self-ideal discrepancy, greater depressive symptoms, and more alcohol-related consequences were positively associated with actual past help-seeking. Alcohol-related problems and normative discrepancy were negatively associated with hypothetical likelihood of utilizing all three help-seeking resources. These results suggest that heavy drinking college students prefer low-threshold intervention options including peer, family, computerized, and brief motivational interventions. Only 36 participants (18.3% of the sample) reported that they had utilized any of the help-seeking options queried, suggesting that campus prevention efforts should include both promoting low-threshold interventions and attempting to increase the salience of alcohol-related risk and the potential utility of changing drinking patterns. PMID:21198220

  13. Help-Seeking for Alcohol-Related Problems in College Students: Correlates and Preferred Resources

    PubMed Central

    Buscemi, Joanna; Murphy, James G.; Martens, Matthew P.; McDevitt-Murphy, Meghan E.; Pederson, Ashley A.; Skidmore, Jessica R.

    2016-01-01

    Despite the development of a variety of efficacious alcohol intervention approaches for college students, few student drinkers seek help. The present study assessed students’ history of help-seeking for alcohol problems as well as their estimates of how likely they would be to use various help-seeking resources, should they wish to change their drinking. Participants were 197 college students who reported recent heavy drinking (46% male, 68.5% White, 27.4% African-American). Participants completed measures related to their drinking and their use (both past use and likelihood of future use) of 14 different alcohol help-seeking options. Repeated measures ANOVAs revealed that students preferred informal help-seeking (e.g., talking to friends and family) over formal (e.g., talking with a counselor or medical provider) and anonymous resources (e.g., internet- or computer-based programs). Higher self-ideal discrepancy, greater depressive symptoms, and more alcohol-related consequences were positively associated with actual past help-seeking. Alcohol-related problems and normative discrepancy were negatively associated with hypothetical likelihood of utilizing all three help-seeking resources. These results suggest that heavy drinking college students prefer low-threshold intervention options including peer, family, computerized, and brief motivational interventions. Only 36 participants (18.3% of the sample) reported that they had utilized any of the help-seeking options queried, suggesting that campus prevention efforts should include both promoting low-threshold interventions and attempting to increase the salience of alcohol-related risk and the potential utility of changing drinking patterns. PMID:21198220

  14. Alcohol-related adverse consequences: cross-cultural variations in attribution process among young adults

    PubMed Central

    Plant, Martin A.; Plant, Moira L.; Miller, Patrick; Kuntsche, Sandra; Gmel, Gerhard

    2008-01-01

    Background: Social norms around what is culturally accepted in terms of alcohol consumption and drunken comportment appear important regarding the acceptance of alcohol-related adverse consequences; however, investigations often neglect to consider differences in terms of attribution. This study aims at assessing cross-cultural differences in the reporting of alcohol-related adverse consequences. It also considers differences across consequences that might explain which type of consequences (mainly acute or mainly chronic) are most affected by an attribution process. Methods: Conditional regression models were estimated based on data from eight European countries participating in the Gender, Alcohol and Culture—An International Study (GENACIS) project. Cases were matched to controls based on usual drinking patterns in order to control for average volume of alcohol and frequency of ‘risky single occasion drinking’ (RSOD). Results: Differences among the patterns of associations between countries and consequences were evident. The distinction between Nordic and other European countries was persistent. A higher variability of associations was observed for some consequences, namely the mainly acute instances. Finally, the Isle of Man and Switzerland showed specific trends with associations across consequences. Conclusion: Reporting of alcohol-related adverse consequences seemed strongly affected by cultural norms. The latter may be exemplified by viewing drinking as ‘time-out’ behaviour. Respondents in countries with a stereotypical history of being ‘dry’ or with a stereotyped ‘binge’ drinking culture were more likely to attribute consequences to their alcohol consumption than people in ‘wet’ countries. This was particularly true for consequences that related to episodic ‘time-out’ heavy drinking. PMID:18287104

  15. Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

    PubMed

    Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

    2015-01-01

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. PMID:24164917

  16. Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers

    PubMed Central

    Meyers, Jacquelyn L.; Shmulewitz, Dvora; Wall, Melanie M.; Keyes, Katherine M.; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J.; Gelernter, Joel; Grant, Bridget F.; Hasin, Deborah

    2013-01-01

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect, parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes “maximum drinks in a day” (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n=1,143) evaluated between 2007–2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks [Mean Differences: 1.50; 1.13 respectively] and AUD severity [Mean Ratios: 0.71; 0.27 respectively]). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (p<0.01) and AUD severity (p<0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared to those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g., those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. PMID:24164917

  17. Neurodevelopmental Outcomes After Cardiac Surgery in Infancy

    PubMed Central

    Stopp, Christian; Wypij, David; Andropoulos, Dean B.; Atallah, Joseph; Atz, Andrew M.; Beca, John; Donofrio, Mary T.; Duncan, Kim; Ghanayem, Nancy S.; Goldberg, Caren S.; Hövels-Gürich, Hedwig; Ichida, Fukiko; Jacobs, Jeffrey P.; Justo, Robert; Latal, Beatrice; Li, Jennifer S.; Mahle, William T.; McQuillen, Patrick S.; Menon, Shaji C.; Pemberton, Victoria L.; Pike, Nancy A.; Pizarro, Christian; Shekerdemian, Lara S.; Synnes, Anne; Williams, Ismee; Bellinger, David C.; Newburger, Jane W.

    2015-01-01

    BACKGROUND: Neurodevelopmental disability is the most common complication for survivors of surgery for congenital heart disease (CHD). METHODS: We analyzed individual participant data from studies of children evaluated with the Bayley Scales of Infant Development, second edition, after cardiac surgery between 1996 and 2009. The primary outcome was Psychomotor Development Index (PDI), and the secondary outcome was Mental Development Index (MDI). RESULTS: Among 1770 subjects from 22 institutions, assessed at age 14.5 ± 3.7 months, PDIs and MDIs (77.6 ± 18.8 and 88.2 ± 16.7, respectively) were lower than normative means (each P < .001). Later calendar year of birth was associated with an increased proportion of high-risk infants (complexity of CHD and prevalence of genetic/extracardiac anomalies). After adjustment for center and type of CHD, later year of birth was not significantly associated with better PDI or MDI. Risk factors for lower PDI were lower birth weight, white race, and presence of a genetic/extracardiac anomaly (all P ≤ .01). After adjustment for these factors, PDIs improved over time (0.39 points/year, 95% confidence interval 0.01 to 0.78; P = .045). Risk factors for lower MDI were lower birth weight, male gender, less maternal education, and presence of a genetic/extracardiac anomaly (all P < .001). After adjustment for these factors, MDIs improved over time (0.38 points/year, 95% confidence interval 0.05 to 0.71; P = .02). CONCLUSIONS: Early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk CHD infants undergo cardiac surgery and survive, a growing population will require significant societal resources. PMID:25917996

  18. Involvement in Intimate Partner Psychological Abuse and Suicide Proneness in College Women: Alcohol Related Problems as a Potential Mediator

    PubMed Central

    Lamis, Dorian A.; Malone, Patrick S.; Langhinrichsen-Rohling, Jennifer

    2010-01-01

    This study examined the relations among involvement in intimate partner psychological abuse, alcohol-related problems, and suicide proneness as measured by the Life Attitudes Schedule – Short Form (LAS-SF) in college women (N = 709). Results revealed that, as expected, being involved in a psychologically abusive relationship was significantly and positively correlated with alcohol-related problems and alcohol-related problems were significantly and positively correlated with suicide proneness. Additionally, the intimate partner psychological abuse involvement-suicide proneness link was significantly mediated by alcohol-related problems. Implications are offered for the improved identification and treatment of young women at risk for suicidal and health-diminishing behaviors. PMID:20544000

  19. The relationship between temporal profiles and alcohol-related problems in University undergraduates: Results from the United Kingdom.

    PubMed

    Cole, Jon C; Andretta, James R; McKay, Michael T

    2016-04-01

    Time perspective is an individual difference variable which assesses the extent to which orientation to the past, present and future affects current behaviors. The present study investigated the viability of temporal profiles and the degree (if any) to which these predict meaningful differences in alcohol-related problems. Participants were undergraduates recruited from a University in the North West of England. Full survey data were available for 455 individuals (aged 18-25; 49.7% male) on (a) time perspective, and (b) alcohol-related problems. Four profiles emerged and were labeled Future-Positive, Present, Past Negative-Future, and Ambivalent. As hypothesized, the Future-Positive profile was associated with the best alcohol-related outcomes. The Present profile was associated with the worst outcomes. This study demonstrates that temporal profiles are associated with alcohol-related problems. PMID:26735914

  20. Alcohol-Related Antigay Aggression: Theoretical Considerations for Individual-and Societal-Level Interventions

    PubMed Central

    Parrott, Dominic J.; Miller, Cameron A.

    2008-01-01

    A substantial literature has identified risk factors for intoxicated aggression and the mechanisms by which these effects are exerted. This theoretical and empirical foundation is a valuable resource for the development of treatment inventions. In contrast, a comparable literature is not available to guide development of clinical interventions for intoxicated antigay aggression. To address this gap in the literature, the present article 1) identifies risk factors and mechanisms pertinent to alcohol-related antigay aggression, 2) advances predictions regarding how alcohol will increase antigay aggression, and 3) reviews societal- and individual-level considerations for intervention based upon these hypotheses. PMID:19938923

  1. Project TENDR: Targeting Environmental Neuro-Developmental Risks The TENDR Consensus Statement

    PubMed Central

    Bennett, Deborah; Bellinger, David C.; Birnbaum, Linda S.; Bradman, Asa; Chen, Aimin; Cory-Slechta, Deborah A.; Engel, Stephanie M.; Fallin, M. Daniele; Halladay, Alycia; Hauser, Russ; Hertz-Picciotto, Irva; Kwiatkowski, Carol F.; Lanphear, Bruce P.; Marquez, Emily; Marty, Melanie; McPartland, Jennifer; Newschaffer, Craig J.; Payne-Sturges, Devon; Patisaul, Heather B.; Perera, Frederica P.; Ritz, Beate; Sass, Jennifer; Schantz, Susan L.; Webster, Thomas F.; Whyatt, Robin M.; Woodruff, Tracey J.; Zoeller, R. Thomas; Anderko, Laura; Campbell, Carla; Conry, Jeanne A.; DeNicola, Nathaniel; Gould, Robert M.; Hirtz, Deborah; Huffling, Katie; Landrigan, Philip J.; Lavin, Arthur; Miller, Mark; Mitchell, Mark A.; Rubin, Leslie; Schettler, Ted; Tran, Ho Luong; Acosta, Annie; Brody, Charlotte; Miller, Elise; Miller, Pamela; Swanson, Maureen; Witherspoon, Nsedu Obot

    2016-01-01

    Summary: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development

  2. The green eyed monster in the bottle: Relationship contingent self-esteem, romantic jealousy, and alcohol-related problems.

    PubMed

    DiBello, Angelo M; Rodriguez, Lindsey M; Hadden, Benjamin W; Neighbors, Clayton

    2015-10-01

    Previous research suggests that both jealousy and relationship contingent self-esteem (RCSE) are related to alcohol use and alcohol-related problems. No work, however, has examined these two constructs together as they relate to motives for alcohol use and alcohol-related problems. The current study aims to build upon emerging literature examining different types of jealousy (i.e., emotional, cognitive, and behavioral), relationship quality (i.e., satisfaction, commitment, closeness), RCSE, and alcohol use. More specifically, the current study aimed to examine the associations between RCSE and drinking to cope and RCSE and alcohol-related problems, in the context of the different types of jealousy. Moreover, the current study aimed to assess whether the associations between RCSE, jealousy, and drinking outcomes vary as a function of relationship quality. Two hundred and seventy seven individuals (87% female) at a large southern university participated in the study. They completed measures of RCSE, relationship satisfaction, commitment, closeness, and jealousy as well as alcohol-related outcomes. Using PROCESS, moderated mediational analyses were used to evaluate different types of jealousy as mediators of the association between RCSE and drinking to cope/alcohol-related problems. Further, we aimed to examine whether relationship quality moderated the association between RCSE and jealousy in predicting alcohol-related variables. Results indicated that cognitive jealousy mediated the association between both RCSE and drinking to cope and RCSE and alcohol-related problems. Further, relationship satisfaction, commitment, and closeness were all found to moderate the association between RSCE and cognitive jealousy such that at lower, but not higher levels of satisfaction, commitment, and closeness, cognitive jealousy mediated the association between RCSE and drinking to cope and RCSE and alcohol-related problems. PMID:26046402

  3. IQ and alcohol-related morbidity and mortality among Swedish men and women: the importance of socioeconomic position

    PubMed Central

    Sjölund, Sara; Hemmingsson, Tomas; Gustafsson, Jan-Eric; Allebeck, Peter

    2015-01-01

    Aims To investigate the association between intelligence in childhood and later risk of alcohol-related disease and death by examining (1) the mediating effect of social position as an adult and (2) gender as a possible moderator. Design Cohort study. Setting and participants 21 809 Swedish men and women, born in 1948 and 1953, from the Swedish “Evaluation Through Follow-up” database were followed until 2006/2007. Measurements IQ was measured in school at the age of 13 and alcohol-related disease and death (International Classification of Disease codes) were followed from 1971 and onwards. Findings We found an increased crude HR of 1.23 (95% CI 1.18 to 1.29) for every decrease in group of IQ test results for alcohol-related admissions and 1.14 (95% CI 1.04 to 1.24) for alcohol-related death. Social position as an adult was found to mediate both outcomes. Gender was not found to moderate the association. However, adjusting for socioeconomic position lowered the risk more among men than among women. Conclusions There was an inverse, graded association between IQ and alcohol-related disease and death, which at least partially was mediated by social position as an adult. For alcohol-related death, complete mediation by socioeconomic position as an adult was found. Gender does not moderate this association. The role of socioeconomic position may differ between the genders. PMID:26163557

  4. Unplanned Drinking and Alcohol-Related Problems: A Preliminary Test of the Model of Unplanned Drinking Behavior

    PubMed Central

    Pearson, Matthew R.; Henson, James M.

    2013-01-01

    Much research links impulsivity with alcohol use and problems. In two studies, unplanned (or impulsive) drinking is assessed directly to determine whether it has direct effects on alcohol use and alcohol-related problems. In study 1, we examined whether unplanned drinking serves as a proximal mediator of the effects of impulsivity-like traits on alcohol-related outcomes. With a sample of 211 college student drinkers, we found that the Unplanned Drinking Scale was significantly related to alcohol use, and perhaps more importantly, had a direct effect on alcohol-related problems even after controlling for frequency and quantity of alcohol use. Further, unplanned drinking partially mediated the effects of negative urgency on alcohol-related problems. In study 2, we examined whether unplanned drinking accounts for unique variance in alcohol-related outcomes when controlling for use of protective behavioral strategies. With a sample of 170 college students, we replicated the findings of Study 1 in that the Unplanned Drinking Scale had a significant direct effect on alcohol-related problems even after controlling for alcohol use; further, this effect was maintained when controlling for use of protective behavioral strategies. Limitations include the modest sample sizes and the cross-sectional design. Future directions for testing the Model of Unplanned Drinking Behavior are proposed. PMID:23276312

  5. The relationship between exposure to alcohol-related content on Facebook and predictors of alcohol consumption among female emerging adults.

    PubMed

    Miller, Joseph; Prichard, Ivanka; Hutchinson, Amanda; Wilson, Carlene

    2014-12-01

    Consuming an unhealthy level of alcohol is a significant problem for some young women. Potential determinants of excess consumption include perceptions of usual consumption among peers-perceptions of what is "normal." The present study examined whether perceptions of social normative endorsement of drinking, operationalized by measures of perceived alcohol consumption of close friends (proximal norms), the consumption of the "average student" (distal norms), and the extent of alcohol-related content posted by peers on Facebook were related to alcohol-related attitudes and self-reported consumption. Female university students (n=129; Mage=21.48 years, SD=3.00) completed an online questionnaire assessing Facebook use, perceived alcohol-related norms, and self-reported alcohol attitudes and consumption. Perceptions of the consumption of the average female student were a negative predictor of attitudes. Positive alcohol attitudes, extent of own alcohol-related photographic posts on Facebook, average female student alcohol consumption, and report of male close friend consumption predicted self-report of own alcohol consumption. Interestingly, female close friend norms failed to predict consumption, whereas male close friend norms predicted consumption but not attitudes, suggesting the possibility of separate cognitive pathways for alcohol-related attitudes and behavior. This study builds on existing research by casting new light on predictors of alcohol-related attitudes, as well as describing the potential role of social networking sites such as Facebook in the formation of social norms and the modulation of drinking behavior. PMID:25489875

  6. Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol-related phenotypes in a Native American community sample

    PubMed Central

    Peng, Qian; Gizer, Ian R.; Libiger, Ondrej; Bizon, Chris; Wilhelmsen, Kirk C.; Schork, Nicholas J.; Ehlers, Cindy L.

    2015-01-01

    Higher rates of alcohol use and other drug-dependence have been observed in some Native American populations relative to other ethnic groups in the U.S. Previous studies have shown that alcohol dehydrogenase (ADH) genes and aldehyde dehydrogenase (ALDH) genes may affect the risk of development of alcohol dependence, and that polymorphisms within these genes may differentially affect risk for the disorder depending on the ethnic group evaluated. We evaluated variations in the ADH and ALDH genes in a large study investigating risk factors for substance use in a Native American population. We assessed ancestry admixture and tested for associations between alcohol-related phenotypes in the genomic regions around the ADH1-7 and ALDH2 and ALDH1A1 genes. Seventy-two (72) ADH variants showed significant evidence of association with a severity level of alcohol drinking-related dependence symptoms phenotype. These significant variants spanned across the entire 7 ADH gene cluster regions. Two significant associations, one in ADH and one in ALDH2, were observed with alcohol dependence diagnosis. Seventeen (17) variants showed significant association with the largest number of alcohol drinks ingested during any 24-hour period. Variants in or near ADH7 were significantly negatively associated with alcohol-related phenotypes, suggesting a potential protective effect of this gene. In addition, our results suggested that a higher degree of Native American ancestry is associated with higher frequencies of potential risk variants and lower frequencies of potential protective variants for alcohol dependence phenotypes. PMID:25270064

  7. Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila

    PubMed Central

    Mellert, David J.; Williamson, W. Ryan; Shirangi, Troy R.; Card, Gwyneth M.; Truman, James W.

    2016-01-01

    Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability “hotspot” depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change. PMID:27223118

  8. Neurodevelopmental consequences of maternal distress: what do we really know?

    PubMed

    Schuurmans, C; Kurrasch, D M

    2013-02-01

    A simple internet search of 'maternal stress and pregnancy' turns up hundreds of hits explaining that an adverse intrauterine environment can affect fetal development and potentially lead to various learning, behavioral, and mood disorders in childhood, as well as complex diseases such as obesity and cardiovascular conditions later in life. Indeed, a growing body of literature now links several intrauterine challenges, including maternal obesity and stress, with adverse developmental outcomes in the child. Over the past 5 years, nearly 5000 publications have explored the consequences of maternal distress on young offspring, a marked increase from the 475 published studies over a comparable period 20 years ago. Yet, despite this explosion of research and widespread warnings to pregnant mothers, we still lack a basic understanding of the pathophysiology linking adverse maternal health to the onset of disease in the child, especially regarding how prenatal and perinatal challenges might affect brain development. Recent studies have begun to explore the cellular basis of the abnormal brain cytoarchitecture associated with fetal exposure to intrauterine challenges. Here, our goal is to review the scientific evidence that maternal distress interferes with key neurodevelopmental steps, as an entry point toward mapping the pathophysiology of pre- and perinatal stress on the unborn child's brain. PMID:23140231

  9. Early Prevention of Severe Neurodevelopmental Behavior Disorders: An Integration

    ERIC Educational Resources Information Center

    Schroeder, Stephen R.; Courtemanche, Andrea

    2012-01-01

    There is a very substantial literature over the past 50 years on the advantages of early detection and intervention on the cognitive, communicative, and social-emotional development of infants and toddlers at risk for developmental delay due to premature birth or social disadvantage. Most of these studies excluded children with severe delays or…

  10. Eyeblink Conditioning: A Non-Invasive Biomarker for Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Reeb-Sutherland, Bethany C.; Fox, Nathan A.

    2015-01-01

    Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…

  11. Individual Differences in Subjective Alcohol Responses and Alcohol-Related Disinhibition

    PubMed Central

    Quinn, Patrick D.; Fromme, Kim

    2016-01-01

    There are important individual differences in acute subjective responses to alcohol, which have often been assessed using self-report measures. There is also evidence of meaningful between-persons variation in alcohol’s disinhibiting effects on behavior, such that some individuals become more impaired on tasks of inhibition than do others after an intoxicating dose. The degree to which subjective alcohol responses correspond with these disinhibition effects is not yet clear. In this study, we tested associations among indices of subjective alcohol responses and their correspondence with sensitivity to alcohol-related disinhibition. We recruited recent-binge-drinking emerging adults (N = 82) for a group-administered, placebo-controlled, within-subject, counterbalanced alcohol challenge in a simulated bar laboratory. Confirmatory factor analyses revealed that a two factor model with several cross-loadings explained associations among the subjective measures well, replicating a differentiation between stimulant-like and sedative-like subjective responses. Controlling sex and placebo performance, participants who reported greater subjective stimulant-like effects—but not sedative-like effects—experienced more alcohol-related disinhibition, as measured by Cued Go/No-Go Task inhibitory failures. This association was small-to-moderate in magnitude. The results of this study highlight the distinction between stimulant-like and sedative-like subjective alcohol effects. They suggest, additionally, that there may be modest commonalities between alcohol’s acute impacts on subjective stimulation and objective disinhibition. PMID:26867000

  12. Latent Trajectory Classes for Alcohol-Related Blackouts from Age 15 to 19 in ALSPAC

    PubMed Central

    Schuckit, Marc A.; Smith, Tom L.; Heron, Jon; Hickman, Matthew; Macleod, John; Munafo, Marcus R.; Kendler, Kenneth S.; Dick, Danielle M.; Davey-Smith, George

    2014-01-01

    Background Alcohol-related blackouts (ARBs) are reported by ~50% of drinkers. While much is known about the prevalence of ARBs in young adults and their cross-sectional correlates, there are few prospective studies regarding their trajectories over time during mid-adolescence. This paper reports latent trajectory classes of alcohol-related blackouts between ages 15 and 19, along with predictors of those patterns. Methods Latent Class Growth Analysis (LCGA) was used to evaluate the pattern of occurrence of ARBs across four time points for 1402 drinking adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multinomial regression analyses evaluated age 15 demography, substance-related items, externalizing characteristics, and estimated peer substance use as predictors of latent class membership. Results ARBs were reported at age 15 in 30% and at age 19 in 74% of these subjects. Four latent trajectory classes were identified: Class 1 (5.1%) reported no blackouts; for Class 2 (29.5%) ARBs rapidly increased with age; for Class 3 (44.9%) blackouts slowly increased; and for Class 4 (20.5%) ARBs were consistently reported. Using Class 2 (rapid increasers) as the reference, predictors of class membership included female sex, higher drinking quantities, smoking, externalizing characteristics, and estimated peer substance involvement (pseudo R2 =.22). Conclusions ARBs were common and repetitive in these young subjects, and predictors of their trajectories over time involved multiple domains representing diverse characteristics. PMID:25516068

  13. A Mediational Model of Racial Discrimination and Alcohol-Related Problems Among African American College Students

    PubMed Central

    Boynton, Marcella H; O’Hara, Ross E; Covault, Jonathan; Scott, Denise; Tennen, Howard

    2014-01-01

    Objective: Racial discrimination has been identified as an important predictor of alcohol-related outcomes for African Americans. The goal of the current study was to extend previously found links between lifetime discrimination, alcohol use, and alcohol problems as well as to elucidate the affective mechanisms underlying these associations, as moderated by gender. Method: A multiple-groups structural equation model was computed using survey data collected from 619 students from a historically Black college/university. Results: The final model provided excellent fit to the data, explaining 6% of the variance in alcohol consumption and 37% of the variance in alcohol problems. Discrimination was a significant predictor of alcohol-related problems but not, by and large, level of use. For men, anger—but not discrimination-specific anger—was a significant partial mediator of the link between discrimination and both alcohol use and alcohol problems. Depression partially mediated the link between discrimination and alcohol problems for both men and women. Conclusions: The results suggest that, for African Americans whose drinking leads to drinking-related problems, discrimination and poor affective self-regulation are highly relevant and predictive factors, especially for men. PMID:24650816

  14. Drinking Reductions following Alcohol-related Sanctions are associated with Social Norms among College Students

    PubMed Central

    Merrill, Jennifer E.; Carey, Kate B.; Reid, Allecia E.; Carey, Michael P.

    2014-01-01

    Students mandated for intervention following an alcohol-related sanction event often reduce their drinking prior to intervention. Knowing the determinants of self-initiated change may help identify intervention targets for individuals who do not reduce their drinking. Guided by self-regulation theory, we tested whether fewer past alcohol consequences and higher descriptive and injunctive norms would be associated with higher levels of post-sanction drinking. College students referred for a campus alcohol violation (N=658, 64% male) reported on their drinking during the month before and after their sanction event. Results show that post-sanction drinking was significantly lower than pre-sanction drinking across four outcomes: (a) drinks per drinking day, (b) drinks per week, (c) peak drinks, and (d) peak blood alcohol concentration (BAC). Hypothesized social influence variables (i.e., descriptive and injunctive norms) were consistently associated with all four drinking outcomes; that is, students who perceived that their friends drank more and held more accepting views of drinking were less reactive to alcohol-related sanctions. Past consequences of drinking did not consistently predict subsequent drinking. Therefore, we conclude that alcohol interventions for mandated students should target both descriptive and injunctive norms to optimize their efficacy. PMID:24274435

  15. Therapeutic reversal of chronic alcohol-related steatohepatitis with the ceramide inhibitor myriocin

    PubMed Central

    Tong, Ming; Longato, Lisa; Ramirez, Teresa; Zabala, Valerie; Wands, Jack R; Monte, Suzanne M

    2014-01-01

    Alcohol-related liver disease (ALD) is associated with steatohepatitis and insulin resistance. Insulin resistance impairs growth and disrupts lipid metabolism in hepatocytes. Dysregulated lipid metabolism promotes ceramide accumulation and oxidative stress, leading to lipotoxic states that activate endoplasmic reticulum (ER) stress pathways and worsen inflammation and insulin resistance. In a rat model of chronic alcohol feeding, we characterized the effects of a ceramide inhibitor, myriocin, on the histopathological and ultrastructural features of steatohepatitis, and the biochemical and molecular indices of hepatic steatosis, insulin resistance and ER stress. Myriocin reduced the severity of alcohol-related steatohepatitis including the abundance and sizes of lipid droplets and mitochondria, inflammation and architectural disruption of the ER. In addition, myriocin-mediated reductions in hepatic lipid and ceramide levels were associated with constitutive enhancement of insulin signalling through the insulin receptor and IRS-2, reduced hepatic oxidative stress and modulation of ER stress signalling mechanisms. In conclusion, ceramide accumulation in liver mediates tissue injury, insulin resistance and lipotoxicity in ALD. Reducing hepatic ceramide levels can help restore the structural and functional integrity of the liver in chronic ALD due to amelioration of insulin resistance and ER stress. However, additional measures are needed to protect the liver from alcohol-induced necroinflammatory responses vis-à-vis continued alcohol abuse. PMID:24456332

  16. Disruption of Alcohol-Related Memories by mTORC1 Inhibition Prevents Relapse

    PubMed Central

    Barak, Segev; Liu, Feng; Hamida, Sami Ben; Yowell, Quinn V.; Neasta, Jeremie; Kharazia, Viktor; Janak, Patricia H.; Ron, Dorit

    2013-01-01

    Relapse to alcohol abuse is a critical clinical issue, frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval, during a memory reconsolidation process that depends on protein synthesis. Here, we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar (CeA) inhibition of mTORC1 during reconsolidation disrupts alcohol-cue associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates play a crucial role in alcohol-related memory reconsolidation, and highlight this pathway as a therapeutic target to prevent relapse. PMID:23792945

  17. Changes in Alcohol-Related Problems After Alcohol Policy Changes in Denmark, Finland, and Sweden*

    PubMed Central

    Bloomfield, Kim; Wicki, Matthias; Gustafsson, Nina-Katri; Mäkelä, Pia; Room, Robin

    2010-01-01

    Objective: European Union travelers' allowances for alcohol import to Denmark, Sweden, and Finland were abolished in 2004. In addition, excise taxes on alcohol were lowered in 2003 and 2005 in Denmark, and in 2004 in Finland. Using northern Sweden as a control site, this study examines whether levels of reported alcohol problems have changed in Denmark, Finland, and southern Sweden as a consequence of these policy changes. Method: Annual cross-sectional surveys were conducted in Denmark, Finland, and Sweden from 2003 to 2006. Five dependency items and seven extrinsic alcohol-related problems were examined. Changes were analyzed within each country/region with logistic regressions and tested for short- and long-term changes. Differential change was also tested between each country and the control site, northern Sweden. Results: Prevalence of alcohol problems decreased over the study period. Only in selected subgroups did problems increase. This mainly occurred in the samples for northern Sweden and Finland, and mostly among older age groups and men. In relation to the control site, however, no increases in problem prevalence were found. Conclusions: Our findings on a decline in reported alcohol problems largely agree with published reports on alcohol consumption over the same period in the study countries. They do not agree, however, with findings on changes in health and social statistics in Finland and Denmark, where some significant increases in alcohol-related harm have been found. PMID:20105411

  18. Effects of prices, civil and criminal sanctions, and law enforcement on alcohol-related mortality.

    PubMed

    Sloan, F A; Reilly, B A; Schenzler, C

    1994-07-01

    Alcohol use has been linked to several causes of death. This study provides an empirical analysis of the effects of various public policies on mortality rates by state and year for the years 1982-88. Causes of death analyzed are: alcohol primary cause; traffic accident; homicides; suicides; falls, fires and other accidents; and contributory cause deaths (cancers of the alimentary tract). We find that increasing the price of alcohol decreases mortality rates for some of the causes, but not for primary cause deaths. Higher excise taxes on cigarettes reduce contributory cause mortality. Dram shop laws have negative and statistically significant effects not only on mortality rates from traffic accidents, but for several of the other causes. There is a need for further analysis to determine how these reductions are achieved. We find no evidence that imposing mandatory minimum jail terms, fines or license revocation for a DUI conviction affects alcohol-related mortality. However, increased police protection decreases mortality rates for several categories, especially homicides and traffic accidents. We find that imposing the death penalty reduces homicide rates. Reductions in alcohol-related mortality may be achieved by implementing a mix of public policies. No single policy is a panacea. PMID:7934053

  19. The Influence of Gender and Sexual Orientation on Alcohol Use and Alcohol-Related Problems

    PubMed Central

    Hughes, Tonda L.; Wilsnack, Sharon C.; Kantor, Lori Wolfgang

    2016-01-01

    Although there are wide differences in alcohol use patterns among countries, men are consistently more likely than women to be drinkers and to drink heavily. Studies of alcohol use among sexual minorities (SMs), however, reflect a more complex picture. Such research has found higher rates of alcohol use and alcohol-related problems among SM persons than among heterosexuals and greater differences between SM and heterosexual women than between SM and heterosexual men. A variety of factors may contribute to differences in alcohol use and alcohol-related problems between men and women and between SM and heterosexual people. An improved understanding of these factors is important to guide prevention and treatment efforts. Although there is a dearth of literature on use of alcohol by SMs in many parts of the world, especially lower- and middle-income countries, we attempt to review and integrate the sparse data that are available from these lower-resourced countries. The global perspective presented in this article is the first attempt to go beyond a general review of literature in the Western world to document the gender paradox in alcohol use among heterosexuals and SMs in diverse countries worldwide. PMID:27159819

  20. [Vojta's method as the early neurodevelopmental diagnosis and therapy concept].

    PubMed

    Banaszek, Grazyna

    2010-01-01

    Vaclav Vojta (1917-2000) developed an early diagnostic method of the neurodevelopmental disorder of infants and came up with therapeutic concept consisting in releasing of global motor complexes by means of the stimulation of proper areas on patients body. In the diagnostics apart from very careful observation of the spontaneous movement of the infant and examination of the reflexes that are characteristic for the first weeks of human's life, Vojta applied the examination of the 7 postural reactions. Presence of the trouble in patterns and dynamics of the postural reactions Vojta called Central Nervous Coordination Disorder--CNCD and regarded as work diagnosis or alarm signal indicating necessity of application of the therapy, especially when asymmetry of the muscle tone and primitive reflexes beyond their physiological appearance period are observed or the number of the abnormal reactions exceeds 5. Global motor complexes as reflex locomotion--crawling and rotation--consist of all the partial motion patterns, which are gradually used by healthy infant in the process of postural and motor ontogenesis. Providing the central nervous system with proper external stimulation allows to, using neuronal plasticity, recreate an access to the human's postural development program and gradually replace pathological motor patterns by those more regular. Exercises repeated several times a day rebuilt support, erectile and vertical mechanisms, improve automatic postural control and phase lower limb movement. Affecting especially on autochtonic muscles of the spine exercises balance synergic cooperation of muscle groups in the trunk and those surrounding key body joints. This way they correct body's posture and peripheral motion and pathology of the outlasted primitive reflexes gradually withdraws. PMID:20509579

  1. Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies.

    PubMed

    Lal, Dennis; Ruppert, Ann-Kathrin; Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G; Kasteleijn-Nolst Trenité, Dorothée; Sonsma, Anja C M; Koeleman, Bobby P; Lindhout, Dick; Weber, Yvonne G; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J; Kunz, Wolfram S; Surges, Rainer; Elger, Christian E; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M; Rosenow, Felix; Neubauer, Bernd A; Reinthaler, Eva M; Zimprich, Fritz; Feucht, Martha; Møller, Rikke S; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Lieb, Wolfgang; Franke, Andre; Strauch, Konstantin; Gieger, Christian; Schurmann, Claudia; Schminke, Ulf; Nürnberg, Peter; Sander, Thomas

    2015-05-01

    Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. PMID:25950944

  2. Burden Analysis of Rare Microdeletions Suggests a Strong Impact of Neurodevelopmental Genes in Genetic Generalised Epilepsies

    PubMed Central

    Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G.; Kasteleijn-Nolst Trenité, Dorothée; Sonsma, Anja C. M.; Koeleman, Bobby P.; Lindhout, Dick; Weber, Yvonne G.; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J.; Kunz, Wolfram S.; Surges, Rainer; Elger, Christian E.; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M.; Rosenow, Felix; Neubauer, Bernd A.; Reinthaler, Eva M.; Zimprich, Fritz; Feucht, Martha; Møller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Lieb, Wolfgang; Franke, Andre; Strauch, Konstantin; Gieger, Christian; Schurmann, Claudia; Schminke, Ulf; Nürnberg, Peter; Sander, Thomas

    2015-01-01

    Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. PMID:25950944

  3. Circulating granulocyte lifespan in compensated alcohol-related cirrhosis: a pilot study.

    PubMed

    Potts, Jonathan R; Farahi, Neda; Heard, Sarah; Chilvers, Edwin R; Verma, Sumita; Peters, Adrien M

    2016-09-01

    Although granulocyte dysfunction is known to occur in cirrhosis, in vivo studies of granulocyte lifespan have not previously been performed. The normal circulating granulocyte survival half-time (G - t½), determined using indium-111 ((111)In)-radiolabeled granulocytes, is ~7 h. In this pilot study, we aimed to measure the in vivo G - t½ in compensated alcohol-related cirrhosis. Sequential venous blood samples were obtained in abstinent subjects with alcohol-related cirrhosis over 24 h post injection (PI) of minimally manipulated (111)In-radiolabeled autologous mixed leukocytes. Purified granulocytes were isolated from each sample using a magnetic microbead-antibody technique positively selecting for the marker CD15. Granulocyte-associated radioactivity was expressed relative to peak activity, plotted over time, and G - t½ estimated from data up to 12 h PI This was compared with normal neutrophil half-time (N - t½), determined using a similar method specifically selecting neutrophils in healthy controls at a collaborating center. Seven patients with cirrhosis (six male, aged 57.8 ± 9.4 years, all Child-Pugh class A) and seven normal controls (three male, 64.4 ± 5.6 years) were studied. Peripheral blood neutrophil counts were similar in both groups (4.6 (3.5 - 5.5) × 10(9)/L vs. 2.8 (2.7 - 4.4) × 10(9)/L, respectively, P = 0.277). G - t½ in cirrhosis was significantly lower than N - t½ in controls (2.7 ± 0.5 h vs. 4.4 ± 1.0 h, P = 0.007). Transient rises in granulocyte and neutrophil-associated activities occurred in four patients from each group, typically earlier in cirrhosis (4-6 h PI) than in controls (8-10 h), suggesting recirculation of radiolabeled cells released from an unidentified focus. Reduced in vivo granulocyte survival in compensated alcohol-related cirrhosis is a novel finding and potentially another mechanism for immune dysfunction in chronic liver disease. Larger studies are needed to

  4. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  5. Structural Brain Abnormalities in Adolescents with Autism Spectrum Disorder and Patients with Attention Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R.; Konrad, Kerstin

    2007-01-01

    Background: Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap…

  6. Consensus diagnostic criteria for fetal alcohol spectrum disorders in Australia: a modified Delphi study

    PubMed Central

    Watkins, Rochelle E; Elliott, Elizabeth J; Mutch, Raewyn C; Payne, Janet M; Jones, Heather M; Latimer, Jane; Russell, Elizabeth; Fitzpatrick, James P; Hayes, Lorian; Burns, Lucinda; Halliday, Jane; D'Antoine, Heather A; Wilkins, Amanda; Peadon, Elizabeth; Miers, Sue; Carter, Maureen; O'Leary, Colleen M; McKenzie, Anne; Bower, Carol

    2012-01-01

    Objective To evaluate health professionals' agreement with components of published diagnostic criteria for fetal alcohol spectrum disorders (FASD) in order to guide the development of standard diagnostic guidelines for Australia. Design A modified Delphi process was used to assess agreement among health professionals with expertise or experience in FASD screening or diagnosis. An online survey, which included 36 Likert statements on diagnostic methods, was administered over two survey rounds. For fetal alcohol syndrome (FAS), health professionals were presented with concepts from the Institute of Medicine (IOM), University of Washington (UW), Centers for Disease Control (CDC), revised IOM and Canadian diagnostic criteria. For partial FAS (PFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD), concepts based on the IOM and the Canadian diagnostic criteria were compared. Setting/participants 130 Australian and 9 international health professionals. Results Of 139 health professionals invited to complete the survey, 103 (74.1%) responded, and 74 (53.2%) completed one or more questions on diagnostic criteria. We found consensus agreement among participants on the diagnostic criteria for FAS, with the UW criteria most commonly endorsed when compared with all other published criteria for FAS. When health professionals were presented with concepts based on the Canadian and IOM diagnostic criteria, we found consensus agreement but no clear preference for either the Canadian or IOM criteria for the diagnosis of PFAS, and no consensus agreement on diagnostic criteria for ARND. We also found no consensus on the IOM diagnostic criteria for ARBD. Conclusions Participants indicated clear support for use of the UW diagnostic criteria for FAS in Australia. These findings should be used to develop guidelines to facilitate improved awareness of, and address identified gaps in the infrastructure for, FASD diagnosis in Australia. PMID

  7. Adolescent alcohol-related risk cognitions: the roles of social norms and social networking sites.

    PubMed

    Litt, Dana M; Stock, Michelle L

    2011-12-01

    The present study examined the impact of socially based descriptive norms on willingness to drink alcohol, drinker prototype favorability, affective alcohol attitudes, and perceived vulnerability for alcohol-related consequences within the Prototype Willingness model. Descriptive norms were manipulated by having 189 young adolescents view experimenter-created profile pages from the social networking site Facebook, which either showed older peers drinking or not. The results provided evidence that descriptive norms for alcohol use, as portrayed by Facebook profiles, significantly impact willingness to use, prototypes, attitudes toward use, and perceived vulnerability. A multiple mediation analysis indicated that prototypes, attitudes, and perceptions of use mediated the relationship between the content of the Facebook profile and willingness. These results indicate that adolescents who perceive that alcohol use is normative, as evidenced by Facebook profiles, are at higher risk for cognitions shown to predict alcohol use than adolescents who do not see alcohol use portrayed as frequently on Facebook. PMID:21644803

  8. Encephalopathy after persistent vomiting: Three cases of non-alcohol-related Wernicke's encephalopathy.

    PubMed

    Antel, K; Singh, N; Chisholm, B; Heckmann, J M

    2015-06-01

    Wernicke's encephalopathy (WE) is a medical emergency. Although WE is commonly viewed in the context of alcoholism, it can be caused by thiamine deficiency secondary to persistent vomiting. Non-alcohol-related WE may be more catastrophic in onset and less likely to present with the classic features than WE with alcoholism as a cause. We describe three cases of WE due to persistent vomiting without alcoholism in patients with hyperemesis gravidarum, drug-induced hyperlactataemia, and an acute gastrointestinal illness in an already malnourished individual. Our cases highlight the importance of recognising WE when undernutrition, which may be caused by gastrointestinal disease or surgery, or malignancy, is compounded by vomiting. Expert guidelines suggest that WE must be considered in the emergency room in any individual with disturbed consciousness of unknown cause. Treatment is with parenteral thiamine before glucose administration. PMID:26716155

  9. Identifying the best scenario for using schematic organizers as integration tools for alcohol-related information.

    PubMed

    Peel, J L; Dansereau, D F; Dees, S

    1993-01-01

    The goal of the present study was to examine scenarios for using two schematic organizers--schematic knowledge maps and conceptual matrices--in integrating episodic and semantic knowledge about alcohol. Seventy students from undergraduate general psychology classes participated for course credit. Participants were assigned to either a schematic organizer group or an essay writing group. These groups were subdivided further into two treatment sequences: episodic/semantic and semantic/episodic. The episodic activity required participants to complete materials using their own alcohol-related experiences, whereas the semantic activity required participants to annotate expert materials. Assessment measures used were consumer-satisfaction questionnaires and free-recall tests. While no preferences were established for any one scenario, the episodic activities were rated higher than the semantic activities regardless of integration sequence. The semantic/episodic integration scenario did produce higher recall scores for the expert information. PMID:8487138

  10. Services for prisoners with alcohol-related problems: a survey of U.K. prisons.

    PubMed

    McMurran, M; Baldwin, S

    1989-09-01

    Offenders have been identified as heavy drinkers who admit to a relationship between drinking and offending. Many prisoners express a desire to reduce their alcohol consumption. The extent of alcohol interventions in U.K. prisons was unknown and so a postal survey was conducted to gather basic information about current work. Of all responding establishments, 91% claimed to provide services for prisoners with alcohol-related problems and 58% gave details of these services. Services are provided mainly by probation officers/social workers, prison officers and Alcoholics Anonymous. Group and individual interventions are described. Service development has been haphazard, lacking central co-ordination. A case is made for appointment of a central facilitator responsible for staff training, establishing a communications network, encouraging new interventions to match clients' needs, encouraging closer links with community workers and guiding evaluative research. PMID:2790268

  11. Legislation on alcohol detection in alcohol-related traffic accidents involving casualties in Japan and Canada.

    PubMed

    Hattori, H; Komura, S; Furuno, J

    1992-06-01

    A comparative study of the law concerning the arrest and conviction of alcohol-related casualty traffic accident was made between Japan and Canada. In Japan, the incidence of alcohol-related traffic accident has declined since 1970, but the number of fatal traffic accidents remains unchanged over the last 6 years, and amount to 9% of the total number of fatalities in traffic accidents. Hence, an effort is being made to reduce this number. According to the Road Traffic Act, a driver can be convicted for drunken driving if his or her blood alcohol level is above 0.5 mg/ml or above 0.25 mg/l in exhaled air, and if driver is judged as a drunken state by sobriety test. Unlike Canada, however, police officer cannot demand a blood sample from a suspected drunken driver. Instead, they must rely on the breath analysis and sobriety test. These tests are considered to be less accurate than blood test. These drawbacks are reflected in a number of court cases which are related to the relationship between alcohol concentration and the state of driving. In Canada, the operation of a motor vehicle with a blood alcohol level of over 0.8 mg/ml is a criminal offense punishable by fine or imprisonment or both, and results in the suspension of driving privileges for 6 months. Initially, a breath alcohol analysis is performed on everyone suspected of motor vehicle after consuming alcohol within the preceding two hours. Subsequently, with the suspect's consent, a police officer is allowed to request a blood sample for further analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1524523

  12. How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.

    PubMed

    de Goeij, Moniek C M; Suhrcke, Marc; Toffolutti, Veronica; van de Mheen, Dike; Schoenmakers, Tim M; Kunst, Anton E

    2015-04-01

    Economic crises are complex events that affect behavioral patterns (including alcohol consumption) via opposing mechanisms. With this realist systematic review, we aimed to investigate evidence from studies of previous or ongoing crises on which mechanisms (How?) play a role among which individuals (Whom?). Such evidence would help understand and predict the potential impact of economic crises on alcohol consumption. Medical, psychological, social, and economic databases were used to search for peer-reviewed qualitative or quantitative empirical evidence (published January 1, 1990-May 1, 2014) linking economic crises or stressors with alcohol consumption and alcohol-related health problems. We included 35 papers, based on defined selection criteria. From these papers, we extracted evidence on mechanism(s), determinant, outcome, country-level context, and individual context. We found 16 studies that reported evidence completely covering two behavioral mechanisms by which economic crises can influence alcohol consumption and alcohol-related health problems. The first mechanism suggests that psychological distress triggered by unemployment and income reductions can increase drinking problems. The second mechanism suggests that due to tighter budget constraints, less money is spent on alcoholic beverages. Across many countries, the psychological distress mechanism was observed mainly in men. The tighter budget constraints mechanism seems to play a role in all population subgroups across all countries. For the other three mechanisms (i.e., deterioration in the social situation, fear of losing one's job, and increased non-working time), empirical evidence was scarce or absent, or had small to moderate coverage. This was also the case for important influential contextual factors described in our initial theoretical framework. This realist systematic review suggests that among men (but not among women), the net impact of economic crises will be an increase in harmful

  13. The effects of chronic smoking on the pathology of alcohol-related brain damage.

    PubMed

    McCorkindale, A N; Sheedy, D; Kril, J J; Sutherland, G T

    2016-06-01

    Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p < 0.007) but no effect on gray matter regions. In contrast, smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p < 0.06). There were no smoking or combinatorial effects on neuronal density in any of the three regions examined. These results do not support the hypothesis that smoking exacerbates alcohol-related brain damage. The trends here support previous studies that alcohol-related brain damage is characterized by focal neuronal loss and generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to

  14. Prospective Effects of Family Cohesion on Alcohol-Related Problems in Adolescence: Similarities and Differences by Race/Ethnicity.

    PubMed

    Reeb, Ben T; Chan, Sut Yee Shirley; Conger, Katherine J; Martin, Monica J; Hollis, Nicole D; Serido, Joyce; Russell, Stephen T

    2015-10-01

    Research increasingly finds that race/ethnicity needs to be taken into account in the modelling of associations between protective factors and adolescent drinking behaviors in order to understand family effects and promote positive youth development. The current study examined racial/ethnic variation in the prospective effects of family cohesion on adolescent alcohol-related problems using a nationally representative sample. Data were drawn from the first two waves of the National Longitudinal Study of Adolescent to Adult Health and included 10,992 (50% female) non-Hispanic Asian, non-Hispanic Black, Latino, and non-Hispanic White 7th-12th graders. Consistent with Hirschi's social control theory of youth delinquency, higher levels of family cohesion predicted lower levels of future adolescent alcohol-related problems, independent of race/ethnicity, sex, age, baseline alcohol-related problems, and family socioeconomic status. Findings from moderation analyses indicated that the magnitude of associations differed across groups such that the protective effect of family cohesion was strongest among White adolescents. For Latino adolescents, family cohesion was not associated with alcohol-related problems. Future longitudinal cross-racial/ethnic research is needed on common and unique mechanisms underlying differential associations between family processes and adolescent high-risk drinking. Understanding these processes could help improve preventive interventions, identify vulnerable subgroups, and inform health policy aimed at reducing alcohol-related health disparities. PMID:25563233

  15. Effects of Ads from a Drug and Alcohol Prevention Campaign on Willingness to Engage in Alcohol-Related Risky Behaviors

    PubMed Central

    Comello, Maria Leonora G.; Slater, Michael D.

    2011-01-01

    Behavioral willingness is conceptualized as a pathway to behavior that is non-deliberative, yet traditional measures require thoughtful deliberation to complete. This study explored non-deliberative measures of alcohol-related willingness to complement recent work on marijuana-related willingness. The study also examined whether ads from a field-tested drug-and-alcohol prevention campaign may have operated by influencing alcohol-related willingness. Participants viewed campaign ads or consumer ads (control). Outcomes were reaction times to make speeded judgments about whether one would engage in risky alcohol-related behaviors. Results showed that campaign ads lowered willingness to play drinking games and (for males) to drive while intoxicated. PMID:21646292

  16. Protective behavioral strategies when drinking alcohol and their relationship to negative alcohol-related consequences in college students.

    PubMed

    Martens, Matthew P; Taylor, Kari K; Damann, Krista M; Page, Jennifer C; Mowry, Emily S; Cimini, M Dolores

    2004-12-01

    Prior research has examined a number of individual characteristics (e.g., gender, family connectedness) that protect individuals from engaging in heavy drinking and experiencing negative alcohol-related consequences, but less is known about specific behavioral strategies that might also serve as protective factors. In this study, 556 undergraduate students completed the National College Health Assessment (American College Health Association, 2000) and answered questions regarding the use of specific protective behavioral strategies (PBS), alcohol consumption, and alcohol-related consequences. Results indicated that less frequent use of PBS was related to a greater likelihood of experiencing negative alcohol-related consequences, even after accounting for the effects of gender and alcohol consumption. These results suggest that PBS may be an important component of both prevention and treatment programs for college students. PMID:15631613

  17. Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

    PubMed

    Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C

    2016-01-01

    that it will provide a useful neurodevelopmental model to complement other models such as maternal immune activation, particularly when combined with other manipulations to produce dual or triple hit models. However, the developmental trajectory of behavioural and neuropathological changes induced by postnatal PCP and their relevance to schizophrenia must be carefully mapped out. Overall, we support further development of dual (or triple) hit models incorporating genetic, neurodevelopmental and appropriate environmental elements in the search for more aetiologically valid animal models of schizophrenia and neurodevelopmental disorders (NDDs). PMID:26510740

  18. Effects of alcohol taxes on alcohol-related disease mortality in New York State from 1969 to 2006

    PubMed Central

    Delcher, Chris; Maldonado-Molina, Mildred M.; Wagenaar, Alexander C.

    2013-01-01

    Objective The relationship of increased alcohol taxes to reductions in alcohol-related harm is well established. Few studies, however, have examined the effects of sudden decreases in alcohol tax rates or effects of narrow tax changes limited to specific beverage types. In the current study, we: (1) examine whether tax increases on spirits have similar effects in reducing alcohol-related disease mortality as increasing taxes on all types of alcoholic beverages simultaneously, and (2) evaluate effects of beer-specific tax decreases in New York State on mortality. Method We used a time-series, quasi-experimental research design, including non-alcohol deaths within New York State and other states’ rates of alcohol-related disease mortality for comparison. The dataset included 456 monthly observations of mortality in New York State over a 38-year period (1969–2006). We used a random-effects approach and included several other important covariates. Results Alcohol-related disease mortality declined by 7.0% after a 1990 tax increase for spirits and beer. A spirits-only tax increase (in 1972) was not significantly associated with mortality but a data anomaly increased error in this effect estimate. Small tax decreases on beer between 1996 and 2006 had no measurable effect on mortality. Doubling the beer tax from $0.11 to $0.22 per gallon, a return to New York State’s 1990 levels, would decrease deaths by an estimated 250 deaths per year. Conclusions Excise tax increases on beer and spirits were associated with reductions in alcohol-related disease mortality. Modifying tax rates on a single beverage type does not appear to be as effective as doing so on multiple alcoholic beverages simultaneously. In New York, small decreases in beer taxes were not significantly associated with alcohol-related disease mortality. PMID:22436591

  19. Dyadic conflict, drinking to cope, and alcohol-related problems: A psychometric study and longitudinal actor-partner interdependence model.

    PubMed

    Lambe, Laura; Mackinnon, Sean P; Stewart, Sherry H

    2015-10-01

    The motivational model of alcohol use posits that individuals may consume alcohol to cope with negative affect. Conflict with others is a strong predictor of coping motives, which in turn predict alcohol-related problems. Two studies examined links between conflict, coping motives, and alcohol-related problems in emerging adult romantic dyads. It was hypothesized that the association between conflict and alcohol-related problems would be mediated by coping-depression and coping-anxiety motives. It was also hypothesized that this would be true for actor (i.e., how individual factors influence individual behaviors) and partner effects (i.e., how partner factors influence individual behaviors) and at the between- (i.e., does not vary over the study period) and within-subjects (i.e., varies over the study period) levels. Both studies examined participants currently in a romantic relationship who consumed ≥12 alcoholic drinks in the past year. Study 1 was cross-sectional using university students (N = 130 students; 86.9% female; M = 21.02 years old, SD = 3.43). Study 2 used a 4-wave, 4-week longitudinal design with romantic dyads (N = 100 dyads; 89% heterosexual; M = 22.13 years old, SD = 5.67). In Study 2, coping-depression motives emerged as the strongest mediator of the conflict-alcohol-related problems association, and findings held for actor effects but not partner effects. Supplemental analyses revealed that this mediational pathway only held among women. Within any given week, alcohol-related problems changed systematically in the same direction between romantic partners. Interventions may wish to target coping-depression drinking motives within couples in response to conflict to reduce alcohol-related problems. PMID:26075735

  20. Cadmium Exposure and Neurodevelopmental Outcomes in U.S. Children

    PubMed Central

    Weuve, Jennifer; Bellinger, David C.; Schwartz, Joel; Lanphear, Bruce; Wright, Robert O.

    2012-01-01

    Background: Low-level environmental cadmium exposure in children may be associated with adverse neurodevelopmental outcomes. Objective: Our aim was to evaluate associations between urinary cadmium concentration and reported learning disability (LD), special education utilization, and attention deficit hyperactivity disorder (ADHD) in U.S. children using National Health and Nutrition Examination Survey (NHANES) data. Methods: We analyzed data from a subset of participants in NHANES (1999–2004) who were 6–15 years of age and had spot urine samples analyzed for cadmium. Outcomes were assessed by parent or proxy-respondent report. We fit multivariable-adjusted logistic regression models to estimate associations between urinary cadmium and the outcomes. Results: When we compared children in the highest quartile of urinary cadmium with those in the lowest quartile, odds ratios adjusted for several potential confounders were 3.21 [95% confidence interval (CI): 1.43, 7.17] for LD, 3.00 (95% CI: 1.12, 8.01) for special education, and 0.67 (95% CI: 0.28, 1.61) for ADHD. There were no significant interactions with sex, but associations with LD and special education were somewhat stronger in males, and the trend in the ADHD analysis was only evident among those with blood lead levels above the median. Conclusions: These findings suggest that children who have higher urinary cadmium concentrations may have increased risk of both LD and special education. Importantly, we observed these associations at exposure levels that were previously considered to be without adverse effects, and these levels are common among U.S. children. PMID:22289429

  1. BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies.

    PubMed

    Borck, Guntram; Hög, Friederike; Dentici, Maria Lisa; Tan, Perciliz L; Sowada, Nadine; Medeira, Ana; Gueneau, Lucie; Thiele, Holger; Kousi, Maria; Lepri, Francesca; Wenzeck, Larissa; Blumenthal, Ian; Radicioni, Antonio; Schwarzenberg, Tito Livio; Mandriani, Barbara; Fischetto, Rita; Morris-Rosendahl, Deborah J; Altmüller, Janine; Reymond, Alexandre; Nürnberg, Peter; Merla, Giuseppe; Dallapiccola, Bruno; Katsanis, Nicholas; Cramer, Patrick; Kubisch, Christian

    2015-02-01

    RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development. PMID:25561519

  2. BRF1 mutations alter RNA polymerase III–dependent transcription and cause neurodevelopmental anomalies

    PubMed Central

    Hög, Friederike; Dentici, Maria Lisa; Tan, Perciliz L.; Sowada, Nadine; Medeira, Ana; Gueneau, Lucie; Thiele, Holger; Kousi, Maria; Lepri, Francesca; Wenzeck, Larissa; Blumenthal, Ian; Radicioni, Antonio; Schwarzenberg, Tito Livio; Mandriani, Barbara; Fischetto, Rita; Morris-Rosendahl, Deborah J.; Altmüller, Janine; Reymond, Alexandre; Nürnberg, Peter; Merla, Giuseppe; Dallapiccola, Bruno; Katsanis, Nicholas; Cramer, Patrick; Kubisch, Christian

    2015-01-01

    RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III–related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development. PMID:25561519

  3. Surgery and Neurodevelopmental Outcome of Very Low Birth Weight Infants

    PubMed Central

    Morriss, Frank H.; Saha, Shampa; Bell, Edward F.; Colaizy, Tarah T.; Stoll, Barbara J.; Hintz, Susan R.; Shankaran, Seetha; Vohr, Betty R.; Hamrick, Shannon E. G.; Pappas, Athina; Jones, Patrick M.; Carlo, Waldemar A.; Laptook, Abbot R.; Van Meurs, Krisa P.; Sánchez, Pablo J.; Hale, Ellen C.; Newman, Nancy S.; Das, Abhik; Higgins, Rosemary D.

    2014-01-01

    IMPORTANCE Reduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine. OBJECTIVE To assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low birth weight infants. DESIGN Retrospective cohort analysis of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998–2009 and evaluated at 18–22 months’ corrected age. SETTING 22 academic neonatal intensive care units. PARTICIPANTS Inclusion criteria were: birth weight 401–1500 g; survival to 12 hours; available for follow-up. Some conditions were excluded. 12 111 infants were included in analyses, 87% of those eligible. EXPOSURES Surgical procedures; surgery also classified by expected anesthesia type as major (general anesthesia) or minor surgery (non-general anesthesia). MAIN OUTCOME MEASURES Multivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted means of Bayley Scales of Infant Development, Second Edition, Mental Developmental Index and Psychomotor Developmental Index for patients born before 2006. RESULTS There were 2186 major, 784 minor and 9141 no surgery patients. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% confidence interval 1.08–1.55). For patients who had major surgery compared with those who had no surgery the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% confidence interval 1.24–1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery

  4. Can screening and brief intervention lead to population-level reductions in alcohol-related harm?

    PubMed

    Heather, Nick

    2012-01-01

    A distinction is made between the clinical and public health justifications for screening and brief intervention (SBI) against hazardous and harmful alcohol consumption. Early claims for a public health benefit of SBI derived from research on general medical practitioners' (GPs') advice on smoking cessation, but these claims have not been realized, mainly because GPs have not incorporated SBI into their routine practice. A recent modeling exercise estimated that, if all GPs in England screened every patient at their next consultation, 96% of the general population would be screened over 10 years, with 70-79% of excessive drinkers receiving brief interventions (BI); assuming a 10% success rate, this would probably amount to a population-level effect of SBI. Thus, a public health benefit for SBI presupposes widespread screening; but recent government policy in England favors targeted versus universal screening, and in Scotland screening is based on new registrations and clinical presentation. A recent proposal for a national screening program was rejected by the UK National Health Service's National Screening Committee because 1) there was no good evidence that SBI led to reductions in mortality or morbidity, and 2) a safe, simple, precise, and validated screening test was not available. Even in countries like Sweden and Finland, where expensive national programs to disseminate SBI have been implemented, only a minority of the population has been asked about drinking during health-care visits, and a minority of excessive drinkers has been advised to cut down. Although there has been research on the relationship between treatment for alcohol problems and population-level effects, there has been no such research for SBI, nor have there been experimental investigations of its relationship with population-level measures of alcohol-related harm. These are strongly recommended. In this article, conditions that would allow a population-level effect of SBI to occur are

  5. Can screening and brief intervention lead to population-level reductions in alcohol-related harm?

    PubMed Central

    2012-01-01

    A distinction is made between the clinical and public health justifications for screening and brief intervention (SBI) against hazardous and harmful alcohol consumption. Early claims for a public health benefit of SBI derived from research on general medical practitioners’ (GPs’) advice on smoking cessation, but these claims have not been realized, mainly because GPs have not incorporated SBI into their routine practice. A recent modeling exercise estimated that, if all GPs in England screened every patient at their next consultation, 96% of the general population would be screened over 10 years, with 70-79% of excessive drinkers receiving brief interventions (BI); assuming a 10% success rate, this would probably amount to a population-level effect of SBI. Thus, a public health benefit for SBI presupposes widespread screening; but recent government policy in England favors targeted versus universal screening, and in Scotland screening is based on new registrations and clinical presentation. A recent proposal for a national screening program was rejected by the UK National Health Service’s National Screening Committee because 1) there was no good evidence that SBI led to reductions in mortality or morbidity, and 2) a safe, simple, precise, and validated screening test was not available. Even in countries like Sweden and Finland, where expensive national programs to disseminate SBI have been implemented, only a minority of the population has been asked about drinking during health-care visits, and a minority of excessive drinkers has been advised to cut down. Although there has been research on the relationship between treatment for alcohol problems and population-level effects, there has been no such research for SBI, nor have there been experimental investigations of its relationship with population-level measures of alcohol-related harm. These are strongly recommended. In this article, conditions that would allow a population-level effect of SBI to occur are

  6. Neurodevelopmental outcome of preterm infants with bronchopulmonary dysplasia.

    PubMed Central

    Gray, P. H.; Burns, Y. R.; Mohay, H. A.; O'Callaghan, M. J.; Tudehope, D. I.

    1995-01-01

    The neurodevelopmental outcome of 78 infants with bronchopulmonary dysplasia (BPD) was compared with that of 78 control infants matched for birthweight. To determine the effect of the severity of BPD, 62 infants requiring oxygen at 36 weeks' postmenstrual age (sBPD) were compared with their matched controls. Infants were followed up to 2 years of age, corrected for prematurity, and were classified for neurological impairment, developmental delay, and neurodevelopmental disability. Seventy six (98%) BPD infants and 71 (91%) controls had follow up data available to two years. Neurological impairment, developmental delay, and neurodevelopmental disability occurred more frequently in infants with BPD than in controls but this was not significant. For infants with sBPD, the increased incidence of neurological impairment and definite developmental delay was not significant when compared with the controls, though neurodevelopmental disability occurred more frequently (odds ratio (OR) 3.6: 95% confidence intervals (CI) 1.1-11.8). Predictors of disability in infants with sBPD included periventricular haemorrhage (OR 19.4: 95% CI 4.3-86.6), ventricular dilatation (OR 12.8: 95% CI 2.9-57.3), and sepsis (OR 5.0: 95% CI 1.3-19.4). Adjusting for the presence of these factors, the association between BPD and disability was no longer apparent (OR 0.9: 95% CI 0.2-3.6). The findings suggest that BPD is not independently associated with adverse neurodevelopmental outcome. PMID:8535867

  7. Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment.

    PubMed

    Vetreno, Ryan P; Hall, Joseph M; Savage, Lisa M

    2011-11-01

    Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone. PMID:21256970

  8. Alcohol-related amnesia and dementia: Animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment

    PubMed Central

    Vetreno, Ryan P.; Hall, Joseph M.; Savage, Lisa M.

    2011-01-01

    Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models—from repeated and chronic ethanol exposure to thiamine deficiency—is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone. PMID:21256970

  9. Does increasing community and liquor licensees' awareness, police activity, and feedback reduce alcohol-related violent crime? A benefit-cost analysis.

    PubMed

    Navarro, Héctor José; Shakeshaft, Anthony; Doran, Christopher M; Petrie, Dennis J

    2013-11-01

    Approximately half of all alcohol-related crime is violent crime associated with heavy episodic drinking. Multi-component interventions are highly acceptable to communities and may be effective in reducing alcohol-related crime generally, but their impact on alcohol-related violent crime has not been examined. This study evaluated the impact and benefit-cost of a multi-component intervention (increasing community and liquor licensees' awareness, police activity, and feedback) on crimes typically associated with alcohol-related violence. The intervention was tailored to weekends identified as historically problematic in 10 experimental communities in NSW, Australia, relative to 10 control ones. There was no effect on alcohol-related assaults and a small, but statistically significant and cost-beneficial, effect on alcohol-related sexual assaults: a 64% reduction in in the experimental relative to control communities, equivalent to five fewer alcohol-related sexual assaults, with a net social benefit estimated as AUD$3,938,218. The positive benefit-cost ratio was primarily a function of the value that communities placed on reducing alcohol-related harm: the intervention would need to be more than twice as effective for its economic benefits to be comparable to its costs. It is most likely that greater reductions in crimes associated with alcohol-related violence would be achieved by a combination of complementary legislative and community-based interventions. PMID:24169411

  10. Does Increasing Community and Liquor Licensees’ Awareness, Police Activity, and Feedback Reduce Alcohol-Related Violent Crime? A Benefit-Cost Analysis

    PubMed Central

    Navarro, Héctor José; Shakeshaft, Anthony; Doran, Christopher M.; Petrie, Dennis J.

    2013-01-01

    Approximately half of all alcohol-related crime is violent crime associated with heavy episodic drinking. Multi-component interventions are highly acceptable to communities and may be effective in reducing alcohol-related crime generally, but their impact on alcohol-related violent crime has not been examined. This study evaluated the impact and benefit-cost of a multi-component intervention (increasing community and liquor licensees’ awareness, police activity, and feedback) on crimes typically associated with alcohol-related violence. The intervention was tailored to weekends identified as historically problematic in 10 experimental communities in NSW, Australia, relative to 10 control ones. There was no effect on alcohol-related assaults and a small, but statistically significant and cost-beneficial, effect on alcohol-related sexual assaults: a 64% reduction in in the experimental relative to control communities, equivalent to five fewer alcohol-related sexual assaults, with a net social benefit estimated as AUD$3,938,218. The positive benefit-cost ratio was primarily a function of the value that communities placed on reducing alcohol-related harm: the intervention would need to be more than twice as effective for its economic benefits to be comparable to its costs. It is most likely that greater reductions in crimes associated with alcohol-related violence would be achieved by a combination of complementary legislative and community-based interventions. PMID:24169411

  11. Preventing Fetal Alcohol Syndrome and Other Alcohol-Related Birth Defects: Teacher's Manual and Student Text. High School Edition.

    ERIC Educational Resources Information Center

    Howard, Elizabeth; And Others

    This teacher's manual presents lesson plans for a high-school instructional unit on Fetal Alcohol Syndrome and its less severe manifestations, Alcohol-Related Birth Defects. The lessons cover alcohol's effects during pregnancy, the history of concern about alcohol's effects, consequences of alcohol use in pregnancy, lifestyle risk reduction, and…

  12. Alcohol-Related Consequences among First-Year University Students: Effectiveness of a Web-Based Personalized Feedback Program

    ERIC Educational Resources Information Center

    Doumas, Diana M.; Nelson, Kinsey; DeYoung, Amanda; Renteria, Camryn Conrad

    2014-01-01

    This study evaluated the effectiveness of a web-based personalized feedback program using an objective measure of alcohol-related consequences. Participants were assigned to either the intervention group or an assessment-only control group during university orientation. Sanctions received for campus alcohol policy violations were tracked over the…

  13. Relationship of Age of First Drink to Alcohol-Related Consequences among College Students with Unhealthy Alcohol Use

    ERIC Educational Resources Information Center

    Rothman, Emily F.; Dejong, William; Palfai, Tibor; Saitz, Richard

    2008-01-01

    This study investigated the relationship between age of first drink (AFD) and a broad range of negative alcohol-related outcomes among college students exhibiting unhealthy alcohol use. We conducted an anonymous on-line survey to collect self-report data from first-year college students at a large northeastern university. Among 1,792 respondents…

  14. Assessing the Representativeness of Population-Sampled Health Surveys Through Linkage to Administrative Data on Alcohol-Related Outcomes

    PubMed Central

    Gorman, Emma; Leyland, Alastair H.; McCartney, Gerry; White, Ian R.; Katikireddi, Srinivasa Vittal; Rutherford, Lisa; Graham, Lesley; Gray, Linsay

    2014-01-01

    Health surveys are an important resource for monitoring population health, but selective nonresponse may impede valid inference. This study aimed to assess nonresponse bias in a population-sampled health survey in Scotland, with a focus on alcohol-related outcomes. Nonresponse bias was assessed by examining whether rates of alcohol-related harm (i.e., hospitalization or death) and all-cause mortality among respondents to the Scottish Health Surveys (from 1995 to 2010) were equivalent to those in the general population, and whether the extent of any bias varied according to sociodemographic attributes or over time. Data from consenting respondents (aged 20–64 years) to 6 Scottish Health Surveys were confidentially linked to death and hospitalization records and compared with general population counterparts. Directly age-standardized incidence rates of alcohol-related harm and all-cause mortality were lower among Scottish Health Survey respondents compared with the general population. For all years combined, the survey-to-population rate ratios were 0.69 (95% confidence interval: 0.61, 0.76) for the incidence of alcohol-related harm and 0.89 (95% confidence interval: 0.83, 0.96) for all-cause mortality. Bias was more pronounced among persons residing in more deprived areas; limited evidence was found for regional or temporal variation. This suggests that corresponding underestimation of population rates of alcohol consumption is likely to be socially patterned. PMID:25227767

  15. Questioning the Value of Realism: Young Adults' Processing of Messages in Alcohol-Related Public Service Announcements and Advertising.

    ERIC Educational Resources Information Center

    Andsager, Julie L.; Austin, Erica Weintraub; Pinkleton, Bruce E.

    2001-01-01

    Finds that: (1) perceived realism and themes that students could identify with are important factors in increasing the salience and persuasiveness of alcohol-related public service announcements (PSAs) among undergraduate students; (2) realistic but logic-based PSAs were not as effective as unrealistic but enjoyable ads; and (3) low production…

  16. Factors Associated with General and Sexual Alcohol-Related Consequences: An Examination of College Students Studying Abroad

    ERIC Educational Resources Information Center

    Hummer, Justin F.; Pedersen, Eric R.; Mirza, Tehniat; LaBrie, Joseph W.

    2010-01-01

    This study contributes to the scarce research on U.S. college students studying abroad by documenting general and sexual negative alcohol-related risks and factors associated with such risk. The manner of drinking (quantity vs. frequency), pre-departure expectations surrounding alcohol use while abroad, culture-related social anxiety, and…

  17. Demographic and Predeparture Factors Associated with Drinking and Alcohol-Related Consequences for College Students Completing Study Abroad Experiences

    ERIC Educational Resources Information Center

    Pedersen, Eric R.; Skidmore, Jessica R.; Aresi, Giovanni

    2014-01-01

    Objective: Study abroad students are at risk for increased and problematic drinking behavior. As few efforts have been made to examine this at-risk population, the authors predicted drinking and alcohol-related consequences abroad from predeparture and site-specific factors. Participants: The sample consisted of 339 students completing study…

  18. A Longitudinal Examination of the Associations between Shyness, Drinking Motives, Alcohol Use, and Alcohol-related Problems

    PubMed Central

    Young, Chelsie M.; DiBello, Angelo M.; Traylor, Zachary K.; Zvolensky, Michael J.; Neighbors, Clayton

    2015-01-01

    Background The current study evaluated the roles of drinking motives and shyness in predicting problem alcohol use over two years. Methods First-year college student drinkers (N=818) completed assessments of alcohol use and related problems, shyness, and drinking motives every six months over a two year period. Results Generalized linear mixed models indicated that shyness was associated with less drinking, but more alcohol-related problems. Further, shyness was associated with coping, conformity, and enhancement drinking motives, but was not associated with social drinking motives. However, when examining coping motives, moderation analyses revealed that social drinking motives were more strongly associated with coping motives among individuals higher in shyness. In addition, coping, conformity, and enhancement motives, but not social motives, mediated associations between shyness and alcohol-related problems over time. Finally, coping motives mediated the association between the interaction of shyness and social motives and alcohol-related problems. Conclusions Together, the results suggest that shy individuals may drink to reduce negative affect, increase positive affect, and fit in with others in social situations, which may then contribute to greater risk for subsequent alcohol-related problems. PMID:26207856

  19. The Hispanic Americans Baseline Alcohol Survey (HABLAS): Acculturation, Birthplace and Alcohol-Related Social Problems across Hispanic National Groups

    ERIC Educational Resources Information Center

    Caetano, Raul; Vaeth, Patrice A. C.; Rodriguez, Lori A.

    2012-01-01

    The purpose of this study was to examine the association between acculturation, birthplace, and alcohol-related social problems across Hispanic national groups. A total of 5,224 Hispanic adults (18+ years) were interviewed using a multistage cluster sample design in Miami, New York, Philadelphia, Houston, and Los Angeles. Multivariate analysis…

  20. Alcohol Expectancies and Evaluations of Aggression in Alcohol-Related Intimate-Partner Verbal and Physical Aggression

    PubMed Central

    Kachadourian, Lorig K; Quigley, Brian M; Leonard, Kenneth E

    2014-01-01

    Objective: Alcohol aggression expectancies have been found to be associated with increases in aggressive behavior. However, research has not consistently examined evaluations of such behavior. This is unfortunate as both expectancies and evaluations may play a role in whether such behavior will occur. Given this, the current study cross-sectionally examined the associations between alcohol aggression expectancies, evaluations of alcohol-related aggression, indicators of excessive drinking, and alcohol-related verbal and physical aggression. Method: The sample consisted of 280 married and cohabiting couples. These couples reported on excessive drinking indicators, alcohol expectancies and evaluations, and alcohol-related verbal and physical aggression during the past year. Results: Findings showed that verbal aggression was positively associated with indicators of excessive drinking among females and with alcohol aggression expectancies for females who evaluated such aggression positively. For males, aggression expectancies and indicators of excessive drinking were positively associated with verbal aggression. For physical aggression, results showed that indicators of excessive drinking and aggression expectancies were associated with physical aggression for females. For males, aggression expectancies were positively associated and evaluations were negatively associated with physical aggression. Conclusions: These findings add to previous research on alcohol aggression expectancies in close relationships and emphasize the importance of considering evaluations of alcohol-related behavior and how they may play a role in intimate-partner violence and aggression. PMID:25208191

  1. Stress and coping mediate relationships between contingent and global self-esteem and alcohol-related problems among college drinkers.

    PubMed

    Tomaka, Joe; Morales-Monks, Stormy; Shamaley, Angelee Gigi

    2013-08-01

    This study examined the hypotheses that contingent self-esteem would be positively associated with alcohol-related problems and that global self-esteem would be negatively associated with such problems. It also examined the hypothesis that high stress and maladaptive coping would mediate these relationships. A sample of college students (n = 399) who were predominantly Hispanic (89%) completed measures of global and contingent self-esteem; stress and coping; and alcohol-related problems. Correlational and latent variable analyses indicated that contingent self-esteem positively related to alcohol-related problems, with maladaptive coping mediating this relationship. In contrast, global self-esteem negatively related to such problems, a relationship that was also mediated by maladaptive coping and stress. Overall, the results highlight the potentially harmful consequences of contingent self-worth and the adaptive nature of non-contingent self-esteem. They also demonstrate the important role that coping plays in mediating self-esteem's associations with alcohol-related problems. PMID:22930540

  2. Unique Direct and Indirect Effects of Impulsivity-Like Traits on Alcohol-Related Outcomes via Protective Behavioral Strategies

    ERIC Educational Resources Information Center

    Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.

    2012-01-01

    In the present study, we examined whether the use of protective behavioral strategies (PBS) mediates the effects of impulsivity-like traits on alcohol-related problems using a sample of 278 college students. Validating the 5-factor model of impulsivity, we showed that each impulsivity-like trait had a distinct pattern of relationships with PBS…

  3. Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites.

    PubMed

    Kalambokis, Georgios N; Mouzaki, Athanasia; Rodi, Maria; Pappas, Konstantinos; Fotopoulos, Andreas; Xourgia, Xanthi; Tsianos, Epameinondas V

    2012-07-01

    Circulating levels of endotoxin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α increase with intestinal bacterial overgrowth and translocation, and are believed to be involved in the pathogenesis of hyperdynamic circulatory syndrome and functional renal failure in patients with advanced cirrhosis. We investigated the effects of the antibiotic rifaximin on systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites. We measured mean arterial pressure, cardiac output (CO) by Doppler ultrasound, systemic vascular resistance (as the ratio of mean arterial pressure:CO), plasma renin activity, levels of plasma aldosterone, the glomerular filtration rate by plasma clearance of technetium-99m-DTPA, natriuresis, levels of plasma endotoxin, and serum levels of IL-6 and TNF-α in 13 patients at baseline and after 4 weeks of treatment with rifaximin. Rifaximin treatment significantly reduced CO and significantly increased systemic vascular resistance, in association with a significant decrease in plasma rennin activity. The therapy also significantly increased the glomerular filtration rate and natriuresis while reducing levels of endotoxin, IL-6, and TNF-α. Intestinal decontamination with rifaximin improved systemic hemodynamics and renal function in patients with advanced cirrhosis. PMID:22391344

  4. The influence of alcohol-specific communication on adolescent alcohol use and alcohol-related consequences.

    PubMed

    Reimuller, Alison; Hussong, Andrea; Ennett, Susan T

    2011-12-01

    Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use. PMID:21667141

  5. Study Protocol: Screening and Treatment of Alcohol-Related Trauma (START) – a randomised controlled trial

    PubMed Central

    2012-01-01

    Background The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. Methods and design The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP) or Treatment as Usual (TAU). The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. Discussion This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma. Trial Registration The trial has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR) and Trial Registration: ACTRN12611000135910. PMID:23106916

  6. Alcohol-related problems: a critical review of the literature and directions in nurse education.

    PubMed

    Arthur, D

    1998-08-01

    It is generally accepted the around 2-5% of the adult population show major signs of alcohol dependence, that alcohol-related harm is experienced by up to 20% of the population, and that approximately 60% drink at risk-free levels. Further prevalence studies show that there are high numbers of problem drinkers who attend general hospital services for reasons other than their alcohol consumption. Nurses are in constant contact with patients who may have an early problem with alcohol but who are admitted for other reasons, and they are in a prime position to comprehensively assess patients (including alcohol screening), develop rapport and provide 'counselling'. Also, university nursing education is propelling nurses toward adoption of independent discipline focused models of care which are increasingly becoming independent of the medical model. Recent trends in the management of problem drinkers suggest that controlled drinking approaches may well offer treatment options to nurses that the traditional abstinence approaches did not. This paper presents a brief overview of the notion of controlled drinking, then critically reviews the nursing research studies and the descriptive literature providing direction for nursing education. Some recent clinical initiatives are discussed which highlight the flaws existing in nursing education, including lack of sufficient curriculum hours and the need for better designed education models and strategies. PMID:9847741

  7. Insulin Resistance, Ceramide Accumulation, and Endoplasmic Reticulum Stress in Human Chronic Alcohol-Related Liver Disease

    PubMed Central

    Longato, Lisa; Ripp, Kelsey; Setshedi, Mashiko; Dostalek, Miroslav; Akhlaghi, Fatemeh; Branda, Mark; Wands, Jack R.; de la Monte, Suzanne M.

    2012-01-01

    Background. Chronic alcohol-related liver disease (ALD) is mediated by insulin resistance, mitochondrial dysfunction, inflammation, oxidative stress, and DNA damage. Recent studies suggest that dysregulated lipid metabolism with accumulation of ceramides, together with ER stress potentiate hepatic insulin resistance and may cause steatohepatitis to progress. Objective. We examined the degree to which hepatic insulin resistance in advanced human ALD is correlated with ER stress, dysregulated lipid metabolism, and ceramide accumulation. Methods. We assessed the integrity of insulin signaling through the Akt pathway and measured proceramide and ER stress gene expression, ER stress signaling proteins, and ceramide profiles in liver tissue. Results. Chronic ALD was associated with increased expression of insulin, IGF-1, and IGF-2 receptors, impaired signaling through IGF-1R and IRS1, increased expression of multiple proceramide and ER stress genes and proteins, and higher levels of the C14, C16, C18, and C20 ceramide species relative to control. Conclusions. In human chronic ALD, persistent hepatic insulin resistance is associated with dysregulated lipid metabolism, ceramide accumulation, and striking upregulation of multiple ER stress signaling molecules. Given the role of ceramides as mediators of ER stress and insulin resistance, treatment with ceramide enzyme inhibitors may help reverse or halt progression of chronic ALD. PMID:22577490

  8. Infant Symbolic Play as an Early Indicator of Fetal Alcohol-Related Deficit

    PubMed Central

    Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Jacobson, Sandra W.

    2010-01-01

    Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. 107 Cape Coloured, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, socio-demographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and IQ and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. By contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver. PMID:20953338

  9. Attention deficit hyperactivity disorder.

    PubMed

    Thapar, Anita; Cooper, Miriam

    2016-03-19

    Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a prevalence of 1·4-3·0%. It is more common in boys than girls. Comorbidity with childhood-onset neurodevelopmental disorders and psychiatric disorders is substantial. ADHD is highly heritable and multifactorial; multiple genes and non-inherited factors contribute to the disorder. Prenatal and perinatal factors have been implicated as risks, but definite causes remain unknown. Most guidelines recommend a stepwise approach to treatment, beginning with non-drug interventions and then moving to pharmacological treatment in those most severely affected. Randomised controlled trials show short-term benefits of stimulant medication and atomoxetine. Meta-analyses of blinded trials of non-drug treatments have not yet proven the efficacy of such interventions. Longitudinal studies of ADHD show heightened risk of multiple mental health and social difficulties as well as premature mortality in adult life. PMID:26386541

  10. Neurodevelopmental Biology Associated with Childhood Sexual Abuse

    ERIC Educational Resources Information Center

    De Bellis, Michael D.; Spratt, Eve G.; Hooper, Stephen R.

    2011-01-01

    Child maltreatment appears to be the single most preventable cause of mental illness and behavioral dysfunction in the United States. Few published studies examine the developmental and the psychobiological consequences of sexual abuse. There are multiple mechanisms through which sexual abuse can cause post-traumatic stress disorder, activate…

  11. Adult Learning Disorders: Contemporary Issues

    ERIC Educational Resources Information Center

    Wolf, Lorraine E., Ed.; Schreiber, Hope E., Ed.; Wasserstein, Jeanette, Ed.

    2008-01-01

    Recent advances in neuroimaging and genetics technologies have enhanced our understanding of neurodevelopmental disorders in adults. The authors in this volume not only discuss such advances as they apply to adults with learning disorders, but also address their translation into clinical practice. One cluster of chapters addresses developmental…

  12. Under-Researched Demographics: Heavy Episodic Drinking and Alcohol-Related Problems Among Asian Americans.

    PubMed

    Iwamoto, Derek Kenji; Kaya, Aylin; Grivel, Margaux; Clinton, Lauren

    2016-01-01

    , traditional norms that may directly pertain to hyperfemininzed Asian-American women, including modesty and sexual fidelity, may protect against heavy episodic drinking (Young et al. 2005). Conversely, the risk for heavy episodic drinking may be enhanced in men who strive to demonstrate traditional notions of masculinity through risk-taking and endorsement of playboy norms (Iwamoto et al. 2010). Although this review has illustrated the contemporary state of research on alcohol use among Asian Americans, it also highlights the significant limitations in this literature. Many of the studies reviewed here have used cross-sectional data, which do not allow researchers to infer causality between the various sociocultural factors and problematic alcohol use. One way of addressing this gap in the existing literature may be to implement longitudinal designs to further understand how the temporal relationship between sociocultural factors, including acculturation and gender norms, may impact alcohol use and alcohol-related problem trajectories. There also is a pressing need to develop greater understanding of within-group differences among U.S.-born and foreign-born Asian Americans as well as among as specific ethnic groups. To date, epidemiological research has largely neglected to examine these significant discrepancies. Given the growing prevalence of alcohol use and alcohol-related problems among Asian-American women (Grant et al. 2004; Iwamoto et al. 2010), studies also should focus on this group and explore how the intersection of gender and culture may influence alcohol use. Finally, the majority of research on this population has been conducted in college samples; therefore, it is important to also examine community samples, including U.S.-born young adults who are not attending college and older adult Asian-American populations. PMID:27159808

  13. Alcohol, drinking pattern and all-cause, cardiovascular and alcohol-related mortality in Eastern Europe.

    PubMed

    Bobak, Martin; Malyutina, Sofia; Horvat, Pia; Pajak, Andrzej; Tamosiunas, Abdonas; Kubinova, Ruzena; Simonova, Galina; Topor-Madry, Roman; Peasey, Anne; Pikhart, Hynek; Marmot, Michael G

    2016-01-01

    Alcohol has been implicated in the high mortality in Central and Eastern Europe but the magnitude of its effect, and whether it is due to regular high intake or episodic binge drinking remain unclear. The aim of this paper was to estimate the contribution of alcohol to mortality in four Central and Eastern European countries. We used data from the Health, Alcohol and Psychosocial factors in Eastern Europe is a prospective multi-centre cohort study in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and six Czech towns. Random population samples of 34,304 men and women aged 45-69 years in 2002-2005 were followed up for a median 7 years. Drinking volume, frequency and pattern were estimated from the graduated frequency questionnaire. Deaths were ascertained using mortality registers. In 230,246 person-years of follow-up, 2895 participants died from all causes, 1222 from cardiovascular diseases (CVD), 672 from coronary heart disease (CHD) and 489 from pre-defined alcohol-related causes (ARD). In fully-adjusted models, abstainers had 30-50% increased mortality risk compared to light-to-moderate drinkers. Adjusted hazard ratios (HR) in men drinking on average ≥60 g of ethanol/day (3% of men) were 1.23 (95% CI 0.95-1.59) for all-cause, 1.38 (0.95-2.02) for CVD, 1.64 (1.02-2.64) for CHD and 2.03 (1.28-3.23) for ARD mortality. Corresponding HRs in women drinking on average ≥20 g/day (2% of women) were 1.92 (1.25-2.93), 1.74 (0.76-3.99), 1.39 (0.34-5.76) and 3.00 (1.26-7.10). Binge drinking increased ARD mortality in men only. Mortality was associated with high average alcohol intake but not binge drinking, except for ARD in men. PMID:26467937

  14. Relative Mortality among Criminals in Norway and the Relation to Drug and Alcohol Related Offenses

    PubMed Central

    Skardhamar, Torbjørn; Skirbekk, Vegard

    2013-01-01

    Background Registered offenders are known to have a higher mortality rate, but given the high proportion of offenders with drug-addiction, particularly among offenders with a custodial sentence, higher mortality is expected. While the level of overall mortality compared to the non-criminal population is of interest in itself, we also estimate the risk of death by criminal records related to substance abuse and other types of criminal acts, and separate between those who receive a prison sentence or not. Methods Age-adjusted relative risks of death for 2000–2008 were studied in a population based dataset. Our dataset comprise the total Norwegian population of 2.9 million individuals aged 15–69 years old in 1999, of whom 10% had a criminal record in the 1992–1999 period. Results Individuals with a criminal record have twice the relative risk (RR) of death of the control group (non-offenders). Males with a record of use/possession of drugs and a prison record have an 11.9 RR (females, 15.6); males with a drug record but no prison record have a 6.9 RR (females 10.5). Males imprisoned for driving under the influence of substances have a 4.4 RR (females 5.6); males with a record of driving under the influence but no prison sentence have a 3.2 RR (females 6.5). Other male offenders with a prison record have a 2.8 RR (females 3.7); other male offenders with no prison record have a 1.7 RR (females 2.3). Conclusion Significantly higher mortality was found for people with a criminal record, also for those without any record of drug use. Mortality is much higher for those convicted of substance-related crimes: more so for drug- than for alcohol-related crimes and for women. PMID:24223171

  15. Interactive and Indirect Effects of Anxiety and Negative Urgency on Alcohol-Related Problems

    PubMed Central

    Menary, Kyle R.; Corbin, William R.; Leeman, Robert F.; Fucito, Lisa M.; Toll, Benjamin A.; DeMartini, Kelly; O’Malley, Stephanie S.

    2015-01-01

    Background Although drinking for tension reduction has long been posited as a risk factor for alcohol-related problems, studies investigating anxiety in relation to risk for alcohol problems have returned inconsistent results, leading researchers to search for potential moderators. Negative urgency (the tendency to become behaviorally dysregulated when experiencing negative affect) is a potential moderator of theoretical interest because it may increase risk for alcohol problems among those high in negative affect. The present study tested a cross-sectional mediated moderation hypothesis whereby an interactive effect of anxiety and negative urgency on alcohol problems is mediated through coping-related drinking motives. Method The study utilized baseline data from a hazardously drinking sample of young adults (N = 193) evaluated for participation in a randomized controlled trial of naltrexone and motivational interviewing for drinking reduction. Results The direct effect of anxiety on physiological dependence symptoms was moderated by negative urgency such that the positive association between anxiety and physiological dependence symptoms became stronger as negative urgency increased. Indirect effects of anxiety and negative urgency on alcohol problems (operating through coping motives) were also observed. Conclusions Although results of the current cross-sectional study require replication using longitudinal data, the findings suggest that the simultaneous presence of anxiety and negative urgency may be an important indicator of risk for AUDs via both direct interactive effects and indirect additive effects operating through coping motives. These findings have potentially important implications for prevention/intervention efforts for individuals who become disinhibited in the context of negative emotional states. PMID:26031346

  16. Predictors of risky alcohol consumption in schoolchildren and their implications for preventing alcohol-related harm

    PubMed Central

    Bellis, Mark A; Hughes, Karen; Morleo, Michela; Tocque, Karen; Hughes, Sara; Allen, Tony; Harrison, Dominic; Fe-Rodriguez, Eduardo

    2007-01-01

    Background While alcohol-related health and social problems amongst youths are increasing internationally, both consumption and associated harms are particularly high in British youth. Youth drinking patterns, including bingeing, frequent drinking and drinking in public spaces, are associated with increased risks of acute (e.g. violence) and long-term (e.g. alcohol-dependence) health problems. Here we examine economic, behavioural and demographic factors that predict these risky drinking behaviours among 15–16 year old schoolchildren who consume alcohol. A cross-sectional survey was conducted among schoolchildren in North West England (n = 10,271) using an anonymous questionnaire delivered in school settings. Analysis utilised logistic regression to identify independent predictors of risky drinking behaviour. Results Of all respondents, 87.9% drank alcohol. Of drinkers, 38.0% usually binged when drinking, 24.4% were frequent drinkers and 49.8% drank in public spaces. Binge, frequent and public drinking were strongly related to expendable income and to individuals buying their own alcohol. Obtaining alcohol from friends, older siblings and adults outside shops were also predictors of risky drinking amongst drinkers. However, being bought alcohol by parents was associated with both lower bingeing and drinking in public places. Membership of youth groups/teams was in general protective despite some association with bingeing. Conclusion Although previous studies have examined predictors of risky drinking, our analyses of access to alcohol and youth income have highlighted eradicating underage alcohol sales and increased understanding of children's spending as key considerations in reducing risky alcohol use. Parental provision of alcohol to children in a family environment may also be important in establishing child-parent dialogues on alcohol and moderating youth consumption. However, this will require supporting parents to ensure they develop only moderate drinking

  17. A Qualitative Study of Service Provision for Alcohol Related Health Issues in Mid to Later Life

    PubMed Central

    Haighton, Catherine; Wilson, Graeme; Ling, Jonathan; McCabe, Karen; Crosland, Ann; Kaner, Eileen

    2016-01-01

    Aims Epidemiological surveys over the last 20 years show a steady increase in the amount of alcohol consumed by older age groups. Physiological changes and an increased likelihood of health problems and medication use make older people more likely than younger age groups to suffer negative consequences of alcohol consumption, often at lower levels. However, health services targeting excessive drinking tend to be aimed at younger age groups. The aim of this study was to gain an in-depth understanding of experiences of, and attitudes towards, support for alcohol related health issues in people aged 50 and over. Methods Qualitative interviews (n = 24, 12 male/12 female, ages 51–90 years) and focus groups (n = 27, 6 male/21 female, ages 50–95 years) were carried out with a purposive sample of participants who consumed alcohol or had been dependent. Findings Participants’ alcohol misuse was often covert, isolated and carefully regulated. Participants tended to look first to their General Practitioner for help with alcohol. Detoxification courses had been found effective for dependent participants but only in the short term; rehabilitation facilities were appreciated but seen as difficult to access. Activities, informal groups and drop-in centres were endorsed. It was seen as difficult to secure treatment for alcohol and mental health problems together. Barriers to seeking help included functioning at a high level, concern about losing positive aspects of drinking, perceived stigma, service orientation to younger people, and fatalistic attitudes to help-seeking. Facilitators included concern about risk of fatal illness or pressure from significant people. Conclusion Primary care professionals need training on improving the detection and treatment of alcohol problems among older people. There is also a compelling need to ensure that aftercare is in place to prevent relapse. Strong preferences were expressed for support to be provided by those who had experienced

  18. Alcohol-related emergency department admissions among adolescents in the Ghent and Sint-Niklaas areas.

    PubMed

    Calle, P; Hautekiet, A; François, H; Sundahl, N; Cornelis, C; Calle, S; Damen, J; Vanbrabant, P; De Turck, B; De Graeve, K; Mpotos, N; De Paepe, P

    2015-10-01

    Alcohol abuse is a major health concern. The aim of this retrospective study was to analyse the alcohol-related emergency department (ED) admissions among adolescents in all hospitals of distinct areas during a 1-year period. In each hospital, all ED patients with a blood alcohol concentration (BAC) of at least 0.5 g/l were surveyed in a standardised way. Of the 3918 included patients, only 146 (3.7%) were < 18  years. The male-to-female ratio was 1.5:1. There was a strong preponderance of weekend and night time admissions. Most of the patients were transported by ambulance (77% of 138 patients with information on this item). The main reason for ED admittance was depressed level of consciousness (64%), trauma (12%), vomiting and/or abdominal pain (12%), agitation or aggression (4%), syncope (4%) and psychological problems (4%). The context of the alcohol intoxication was related to some kind of festivity in 85%, mental problems in 14% and chronic abuse in 1%. Median BAC values (and range) were 2.08 g/l (0.73-3.70 g/l) for boys and 1.51 g/l (0.73-2.90 g/l) for girls. Most patients (87%) could be discharged home within 24  hours. Our study confirms that problematic alcohol use leading to ED admissions starts in adolescence. Although the numbers of cases below 18 years are low when compared to adults, the phenomenon is alarming as it is associated with substantial health problems. Therefore, Belgium urgently needs a global national alcohol plan, with youngsters being one of the target groups. PMID:25984783

  19. 10 Projects for Preventing Fetal Alcohol Syndrome and Other Alcohol-Related Birth Defects and Have You Heard about Alcohol and Pregnancy.

    ERIC Educational Resources Information Center

    Adams, Jerry; And Others

    A set of two pamphlets is presented on the topic of Fetal Alcohol Syndrome and Alcohol-Related Birth Defects. "Ten Projects for Preventing Fetal Alcohol Syndrome and Other Alcohol-Related Birth Defects" provides ideas and materials for students and others to use in educating the public about the dangers of alcohol use during pregnancy. It offers…

  20. Neurodevelopmental Effects of Early Deprivation in Postinstitutionalized Children

    ERIC Educational Resources Information Center

    Pollak, Seth D.; Nelson, Charles A.; Schlaak, Mary F.; Roeber, Barbara J.; Wewerka, Sandi S.; Wiik, Kristen L.; Frenn, Kristin A.; Loman, Michelle M.; Gunnar, Megan R.

    2010-01-01

    The neurodevelopmental sequelae of early deprivation were examined by testing (N = 132) 8- and 9-year-old children who had endured prolonged versus brief institutionalized rearing or rearing in the natal family. Behavioral tasks included measures that permit inferences about underlying neural circuitry. Children raised in institutionalized…

  1. Update on the Role of Environmental Toxins in Neurodevelopmental Disabilities

    ERIC Educational Resources Information Center

    Kouris, Steven

    2007-01-01

    Toxic exposures during pregnancy and early childhood continue to play an important role as a preventable cause of neurodevelopmental disabilities in the U.S. and around the world. Identifying and eliminating these toxins should be a priority, but the task is made exceedingly difficult due to the severe limits of scientific knowledge in this area…

  2. Neurodevelopmental Problems in Maltreated Children Referred with Indiscriminate Friendliness

    ERIC Educational Resources Information Center

    Kocovska, Eva; Puckering, Christine; Follan, Michael; Smillie, Maureen; Gorski, Charlotta; Barnes, James; Wilson, Philip; Young, David; Lidstone, Emma; Pritchett, Rachel; Hockaday, Harriet; Minnis, Helen

    2012-01-01

    We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological…

  3. Pharmacogenetics of the Neurodevelopmental Impact of Anticancer Chemotherapy

    ERIC Educational Resources Information Center

    Robaey, Philippe; Krajinovic, Maja; Marcoux, Sophie; Moghrabi, Albert

    2008-01-01

    Pharmacogenetics holds the promise of minimizing adverse neurodevelopmental outcomes of cancer patients by identifying patients at risk, enabling the individualization of treatment and the planning of close follow-up and early remediation. This review focuses first on methotrexate, a drug often implicated in neurotoxicity, especially when used in…

  4. Neurodevelopmental outcome after cardiac surgery utilizing cardiopulmonary bypass in children

    PubMed Central

    Naguib, Aymen N.; Winch, Peter D.; Tobias, Joseph D.; Yeates, Keith O.; Miao, Yongjie; Galantowicz, Mark; Hoffman, Timothy M.

    2015-01-01

    Introduction: Modulating the stress response and perioperative factors can have a paramount impact on the neurodevelopmental outcome of infants who undergo cardiac surgery utilizing cardiopulmonary bypass. Materials and Methods: In this single center prospective follow-up study, we evaluated the impact of three different anesthetic techniques on the neurodevelopmental outcomes of 19 children who previously underwent congenital cardiac surgery within their 1st year of life. Cases were done from May 2011 to December 2013. Children were assessed using the Stanford-Binet Intelligence Scales (5th edition). Multiple regression analysis was used to test different parental and perioperative factors that could significantly predict the different neurodevelopmental outcomes in the entire cohort of patients. Results: When comparing the three groups regarding the major cognitive scores, a high-dose fentanyl (HDF) patients scored significantly higher than the low-dose fentanyl (LDF) + dexmedetomidine (DEX) (LDF + DEX) group in the quantitative reasoning scores (106 ± 22 vs. 82 ± 15 P = 0.046). The bispectral index (BIS) value at the end of surgery for the -LDF group was significantly higher than that in LDF + DEX group (P = 0.011). For the entire cohort, a strong correlation was seen between the standard verbal intelligence quotient (IQ) score and the baseline adrenocorticotropic hormone level, the interleukin-6 level at the end of surgery and the BIS value at the end of the procedure with an R2 value of 0.67 and P < 0.04. There was an inverse correlation between the cardiac Intensive Care Unit length of stay and the full-scale IQ score (R = 0.4675 and P 0.027). Conclusions: Patients in the HDF group demonstrated overall higher neurodevelopmental scores, although it did not reach statistical significance except in fluid reasoning scores. Our results may point to a possible correlation between blunting the stress response and improvement of the neurodevelopmental outcome. PMID

  5. Relationship of age of first drink to alcohol-related consequences among college students with unhealthy alcohol use.

    PubMed

    Rothman, Emily F; DeJong, William; Palfai, Tibor; Saitz, Richard

    2008-01-01

    This study investigated the relationship between age of first drink (AFD) and a broad range of negative alcohol-related outcomes among college students exhibiting unhealthy alcohol use. We conducted an anonymous on-line survey to collect self-report data from first-year college students at a large northeastern university. Among 1,792 respondents who reported ever drinking, 14% reported an AFD before age 14. These early onset drinkers were more likely than later onset drinkers to report frequent drinking, heavy drinking, and other unhealthy alcohol use behaviors. Among the subset of drinkers with unhealthy alcohol use (36%), early drinkers were more likely than later onset drinkers to report experiencing five out of 13 alcohol-related consequences, including driving while intoxicated, missing work or school due to drinking, getting into trouble at work or school due to drinking, receiving lower grades than they should have due to drinking, and developing a tolerance to alcohol. PMID:19042317

  6. Applying the Attention-Allocation Model to the Explanation of Alcohol-Related Aggression: Implications for Prevention

    PubMed Central

    Giancola, Peter R.; Josephs, Robert A.; DeWall, C. Nathan; Gunn, Rachel L.

    2009-01-01

    The primary purpose of this article is to apply the attention allocation model (AAM; Steele & Josephs, 1990) to the explanation, as well as the prevention, of alcohol-related violence. The AAM contends that alcohol has a “myopic” effect on attentional capacity that presumably facilitates aggression by narrowing attentional focus on the most salient provocative cues, that are naturally present in hostile situations, rather than less salient inhibitory cues. Data are presented to demonstrate support for the AAM with regard to alcohol-related aggression. The model has also been expanded to suggest some intermediary mechanisms that may account for how distracting attention away from provocative cues might be involved in the reduction of aggression. Finally, a number of practical suggestions are put forth regarding how the AAM can be applied to the prevention of intoxicated aggression. PMID:19938917

  7. Childhood Household Dysfunction, Social Inequality and Alcohol Related Illness in Young Adulthood. A Swedish National Cohort Study

    PubMed Central

    Gauffin, Karl; Hjern, Anders; Vinnerljung, Bo; Björkenstam, Emma

    2016-01-01

    The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973–82 (n = 872 912), which was followed from age 18 to 29–40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7–2.5], two CHD indicators 5.6 [4.4–7.1], three or more indicators 9.4 [7.1–12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks–those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9–14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4–1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage. PMID:26991657

  8. Examining the relationship between parenting types and patterns of student alcohol-related behavior during the transition to college

    PubMed Central

    Abar, Caitlin C.

    2011-01-01

    Objective The present study sought to examine parenting influences on student alcohol use through the use of a holistic, person-centered approach in order to accomplish three distinct research aims: (1) identify groups of college students with unique profiles of perceived parenting characteristics; (2) identify groups of college students with unique profiles of alcohol-related correlates; and (3) examine the extent to which profiles of perceived parenting characteristics are associated with profiles of college alcohol-related risk. Method A sample of 1,153 first-year university students (17 – 20 years-of-age) was assessed on a host of perceived parenting and self-reported alcohol-related items. Results Four profiles of perceived parenting (High Quality, High Monitoring, Anti-Alcohol, Pro-Alcohol) were found using latent profile analysis (LPA). Five profiles of student alcohol-related characteristics (Abstainers, Past Drinkers, Light Drinkers, High Risk Drinkers, Extreme Risk Drinkers) were also found using LPA. Latent transition analysis illustrated that students who perceived their parents as belonging to the Pro-Alcohol profile had much higher probabilities of belonging in the High Risk Drinker or Extreme Risk Drinker profiles than students in all other perceived parenting profiles. Conclusions In addition to alcohol-specific parenting characteristics, aspects of parent-teen relationship quality may also be integral in the prevention of college alcohol misuse. Finally, this study observed complex patterns of parenting and alcohol behaviors, such that the profiles could be interpreted as qualitatively distinct types of individuals. These unique profiles suggest that a targeted approach reflecting the profiles found in the current study might greatly enhance prevention program efficacy. PMID:21842968

  9. Childhood Household Dysfunction, Social Inequality and Alcohol Related Illness in Young Adulthood. A Swedish National Cohort Study.

    PubMed

    Gauffin, Karl; Hjern, Anders; Vinnerljung, Bo; Björkenstam, Emma

    2016-01-01

    The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973-82 (n = 872,912), which was followed from age 18 to 29-40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7-2.5], two CHD indicators 5.6 [4.4-7.1], three or more indicators 9.4 [7.1-12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks-those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9-14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4-1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage. PMID:26991657

  10. Antisocial personality disorder, alcohol, and aggression.

    PubMed

    Moeller, F G; Dougherty, D M

    2001-01-01

    Epidemiologic studies and laboratory research consistently link alcohol use with aggression. Not all people, however, exhibit increased aggression under the influence of alcohol. Recent research suggests that people with antisocial personality disorder (ASPD) may be more prone to alcohol-related aggression than people without ASPD. As a group, people with ASPD have higher rates of alcohol dependence and more alcohol-related problems than people without ASPD. Likewise, in laboratory studies, people with ASPD show greater increases in aggressive behavior after consuming alcohol than people without ASPD. The association between ASPD and alcohol-related aggression may result from biological factors, such as ASPD-related impairments in the functions of certain brain chemicals (e.g., serotonin) or in the activities of higher reasoning, or "executive," brain regions. Alternatively, the association between ASPD and alcohol-related aggression may stem from some as yet undetermined factor(s) that increase the risk for aggression in general. PMID:11496966

  11. The Alcohol Improvement Programme: Evaluation of an Initiative to Address Alcohol-Related Health Harm in England

    PubMed Central

    Thom, Betsy; MacGregor, Susanne; Godfrey, Christine; Herring, Rachel; Lloyd, Charlie; Tchilingirian, Jordan; Toner, Paul

    2013-01-01

    Aims: The evaluation aimed to assess the impact of The Alcohol Improvement Programme (AIP). This was a UK Department of Health initiative (April 2008–March 2011) aiming to contribute to the reduction of alcohol-related harm as measured by a reduction in the rate of increase in alcohol-related hospital admissions (ARHAs). Methods: The evaluation (March 2010–September 2011) used a mix of qualitative and quantitative methods to assess the impact of the AIP on ARHAs, to describe and assess the process of implementation, and to identify elements of the programme which might serve as a ‘legacy’ for the future. Results: There was no evidence that the AIP had an impact on reducing the rise in the rate of ARHAs. The AIP was successfully delivered, increased the priority given to alcohol-related harm on local policy agendas and strengthened the infrastructure for the delivery of interventions. Conclusion: Although there was no measurable short-term impact on the rise in the rate of ARHAs, the AIP helped to set up a strategic response and a delivery infrastructure as a first, necessary step in working towards that goal. There are a number of valuable elements in the AIP which should be retained and repackaged to fit into new policy contexts. PMID:23729674

  12. Associations between depression, distress tolerance, delay discounting, and alcohol-related problems in European American and African American college students.

    PubMed

    Dennhardt, Ashley A; Murphy, James G

    2011-12-01

    Although levels of heavy drinking and alcohol-related problems are high in college students, there is significant variability in the number and type of problems experienced, even among students who drink heavily. African American students drink less and experience fewer alcohol-related problems than European American students, but are still at risk, and little research has investigated the potentially unique patterns and predictors of problems among these students. Depression, distress tolerance, and delay discounting have been implicated in adult substance abuse and may be important predictors of alcohol problem severity among college students. We examined the relationship between these variables and alcohol-related problems among African American and European American students (N = 206; 53% female; 68% European American; 28% African American) who reported recent heavy drinking. In regression models that controlled for drinking level, depression, distress tolerance, and delay discounting were associated with alcohol problems among African American students, but only depression was associated with alcohol problems among European American students. These results suggest that negative affect is a key risk factor for alcohol problems among college student drinkers. For African American students, the inability to tolerate negative emotions and to organize their behavior around future outcomes may also be especially relevant risk factors. PMID:21988480

  13. The Role of Alcohol Perceptions as Mediators Between Personality and Alcohol-Related Outcomes Among Incoming College-Student Drinkers

    PubMed Central

    Hustad, John T. P.; Pearson, Matthew R.; Neighbors, Clayton; Borsari, Brian

    2014-01-01

    After high school, college students escalate their drinking at a faster rate than their noncollege-attending peers, and alcohol use in high school is one of the strongest predictors of alcohol use in college. Therefore, an improved understanding of the role of predictors of alcohol use during the critical developmental period when individuals transition to college has direct clinical implications to reduce alcohol-related harms. We used path analysis in the present study to examine the predictive effects of personality (e.g., impulsivity, sensation seeking, hopelessness, and anxiety sensitivity) and three measures of alcohol perception: descriptive norms, injunctive norms, and perceptions regarding the perceived role of drinking in college on alcohol-related outcomes. Participants were 490 incoming freshmen college students. Results indicated that descriptive norms, injunctive norms, and the role of drinking largely mediated the effects of personality on alcohol outcomes. In contrast, both impulsivity and hopelessness exhibited direct effects on alcohol-related problems. The perceived role of drinking was a particularly robust predictor of outcomes and mediator of the effects of personality traits, including sensation seeking and impulsivity on alcohol outcomes. The intertwined relationships observed in this study between personality factors, descriptive norms, injunctive norms, and the role of drinking highlight the importance of investigating these predictors simultaneously. Findings support the implementation of interventions that target these specific perceptions about the role of drinking in college. PMID:24467197

  14. Epigenetic mechanisms in neurodevelopmental and neurodegenerative disease

    PubMed Central

    Jakovcevski, Mira; Akbarian, Schahram

    2013-01-01

    The exploration of brain epigenomes, which consist of various types of DNA methylation and covalent histone modifications, is providing new and unprecedented insights into the mechanisms of normal neural development, neurological disease and aging. Traditionally, chromatin defects in brain were considered static lesions of early development that occurred in the context of rare genetic syndromes but it is now clear that mutations and maladaptations of the epigenetic machinery cover a much wider continuum, including adult-onset neurodegenerative disease. Here, we describe how recent advances in neuroepigenetics have contributed to an improved mechanistic understanding of developmental and degenerative brain disorders, as well as how they could influence the development of future therapies for these conditions. PMID:22869198

  15. De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features.

    PubMed

    Okur, Volkan; Cho, Megan T; Henderson, Lindsay; Retterer, Kyle; Schneider, Michael; Sattler, Shannon; Niyazov, Dmitriy; Azage, Meron; Smith, Sharon; Picker, Jonathan; Lincoln, Sharyn; Tarnopolsky, Mark; Brady, Lauren; Bjornsson, Hans T; Applegate, Carolyn; Dameron, Amy; Willaert, Rebecca; Baskin, Berivan; Juusola, Jane; Chung, Wendy K

    2016-07-01

    Whole exome sequencing (WES) can be used to efficiently identify de novo genetic variants associated with genetically heterogeneous conditions including intellectual disabilities. We have performed WES for 4102 (1847 female; 2255 male) intellectual disability/developmental delay cases and we report five patients with a neurodevelopmental disorder associated with developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and dysmorphic features in whom we have identified de novo missense and canonical splice site mutations in CSNK2A1, the gene encoding CK2α, the catalytic subunit of protein kinase CK2, a ubiquitous serine/threonine kinase composed of two regulatory (β) and two catalytic (α and/or α') subunits. Somatic mutations in CSNK2A1 have been implicated in various cancers; however, this is the first study to describe a human condition associated with germline mutations in any of the CK2 subunits. PMID:27048600

  16. Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

    PubMed Central

    Pappas, Samuel S.; Leventhal, Daniel K.; Albin, Roger L.; Dauer, William T.

    2014-01-01

    This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role—Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. PMID:24947237

  17. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

    PubMed Central

    Whitcomb, David C.; LaRusch, Jessica; Krasinskas, Alyssa M.; Klei, Lambertus; Smith, Jill P.; Brand, Randall E.; Neoptolemos, John P.; Lerch, Markus M.; Tector, Matt; Sandhu, Bimaljit S.; Guda, Nalini M.; Orlichenko, Lidiya; Alkaade, Samer; Amann, Stephen T.; Anderson, Michelle A.; Baillie, John; Banks, Peter A.; Conwell, Darwin; Coté, Gregory A.; Cotton, Peter B.; DiSario, James; Farrer, Lindsay A.; Forsmark, Chris E.; Johnstone, Marianne; Gardner, Timothy B.; Gelrud, Andres; Greenhalf, William; Haines, Jonathan L.; Hartman, Douglas J.; Hawes, Robert A.; Lawrence, Christopher; Lewis, Michele; Mayerle, Julia; Mayeux, Richard; Melhem, Nadine M.; Money, Mary E.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Pericak-Vance, Margaret A.; Romagnuolo, Joseph; Schellenberg, Gerard D.; Sherman, Stuart; Simon, Peter; Singh, Vijay K.; Slivka, Adam; Stolz, Donna; Sutton, Robert; Weiss, Frank Ulrich; Wilcox, C. Mel; Zarnescu, Narcis Octavian; Wisniewski, Stephen R.; O'Connell, Michael R.; Kienholz, Michelle L.; Roeder, Kathryn; Barmada, M. Michael; Yadav, Dhiraj; Devlin, Bernie; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Baldwin, Clinton T.; Barber, Robert; Barnes, Lisa L.; Beach, Thomas G.; Beecham, Gary W.; Beekly, Duane; Bennett, David A.; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boxer, Adam; Burke, James R.; Buxbaum, Joseph D.; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carney, Regina M.; Carroll, Steven L.; Chui, Helena C.; Clark, David G.; Cribbs, David H.; Crocco, Elizabeth A.; Cruchaga, Carlos; DeCarli, Charles; Demirci, F. Yesim; Dick, Malcolm; Dickson, Dennis W.; Duara, Ranjan; Ertekin-Taner, Nilufer; Faber, Kelley M.; Fallon, Kenneth B.; Farlow, Martin R.; Ferris, Steven; Foroud, Tatiana M.; Frosch, Matthew P.; Galasko, Douglas R.; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H.; Ghetti, Bernardino; Gilbert, John R.; Gilman, Sid; Glass, Jonathan D.; Goate, Alison M.; Graff-Radford, Neill R.; Green, Robert C.; Growdon, John H.; Hakonarson, Hakon; Hamilton-Nelson, Kara L.; Hamilton, Ronald L.; Harrell, Lindy E.; Head, Elizabeth; Honig, Lawrence S.; Hulette, Christine M.; Hyman, Bradley T.; Jicha, Gregory A.; Jin, Lee-Way; Jun, Gyungah; Kamboh, M. Ilyas; Karydas, Anna; Kaye, Jeffrey A.; Kim, Ronald; Koo, Edward H.; Kowall, Neil W.; Kramer, Joel H.; Kramer, Patricia; Kukull, Walter A.; LaFerla, Frank M.; Lah, James J.; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lin, Chiao-Feng; Lieberman, Andrew P.; Lopez, Oscar L.; Lunetta, Kathryn L.; Lyketsos, Constantine G.; Mack, Wendy J.; Marson, Daniel C.; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah C.; Masliah, Eliezer; McKee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Montine, Thomas J.; Morris, John C.; Murrell, Jill R.; Naj, Adam C.; Olichney, John M.; Parisi, Joseph E.; Peskind, Elaine; Petersen, Ronald C.; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray; Reiman, Eric M.; Reisberg, Barry; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rosen, Howard J.; Rosenberg, Roger N.; Sano, Mary; Saykin, Andrew J.; Schneider, Julie A.; Schneider, Lon S.; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vardarajan, Badri N.; Vinters, Harry V.; Vonsattel, Jean Paul; Wang, Li-San; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Williamson, Jennifer; Woltjer, Randall L.; Wright, Clinton B.; Younkin, Steven G.; Yu, Chang-En; Yu, Lei

    2012-01-01

    Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07. PMID:23143602

  18. Post-deployment screening and referral for risky alcohol use and subsequent alcohol-related and injury diagnoses, active component, U.S. Armed Forces, 2008-2014.

    PubMed

    Hurt, Lee

    2015-07-01

    Risky alcohol use among service members is a threat to both military readiness and the health of service members. This report describes an analysis using the Defense Medical Surveillance System (DMSS) to identify all active component service members who returned from deployment and completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) alcohol use screen as part of the Post Deployment Health Assessment (PDHA) and Post Deployment Health Reassessment (PDHRA) during 2008-2014. This analysis identified that 3.4% of PDHA forms and 4.8% of PDHRA forms completed indicated severe risk for alcohol abuse, defined as an AUDIT-C score of 8 or higher. Among those at severe risk on the PDHRA who were not already under care for alcohol abuse, only 37.7% received a referral for treatment: 21.7% to primary care, 13.4% to behavioral health in primary care, 7.5% to mental health specialty care, and 5.6% to a substance abuse program. Referrals for treatment for those at severe risk were lower than their respective counterparts among males, white non-Hispanics, members of the Air Force, junior officers, and pilots/air crew. There were significant trends of increasing frequencies of subsequent injury and alcohol-related conditions as alcohol use levels increased. PMID:26207410

  19. Mutations in KPTN Cause Macrocephaly, Neurodevelopmental Delay, and Seizures

    PubMed Central

    Baple, Emma L.; Maroofian, Reza; Chioza, Barry A.; Izadi, Maryam; Cross, Harold E.; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A.; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E.; Kessels, Michael M.; Crosby, Andrew H.

    2014-01-01

    The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. PMID:24239382

  20. Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures.

    PubMed

    Baple, Emma L; Maroofian, Reza; Chioza, Barry A; Izadi, Maryam; Cross, Harold E; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E; Kessels, Michael M; Crosby, Andrew H

    2014-01-01

    The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. PMID:24239382

  1. Neurodevelopmental outcome of preterm babies of 1999-2009.

    PubMed

    Huggard, D; Slevin, M; Vavasseur, C

    2014-06-01

    The Bayley scale of infant development is employed as the performance indicator at 2 years corrected gestational age for high risk paediatric groups. We compare neurodevelopmental outcomes in two cohorts of VLBW infants born in 1999 to a cohort born a decade later, while also examining the challenges of direct comparison of modified scales: BSID-II (2nd edition of the scales) with Bayley-III, BSID-II was used in the 1999 group and Bayley-III for the 2009 cohort. We demonstrated that over a ten year period there was an improvement in neurodevelopmental scores achieved in VLBW babies. Overall there was almost an 8 point increase in the cognitive scores from the 2009 cohort compared with the 1999 cohort in this time period. The mean motor score increased by 6 points when comparing 1999 and 2009. However we highlight the difficulties in comparing developmental scales, and consider whether Bayley-III overestimates developmental ability? PMID:24988830

  2. Maternal Hypothyroxinemia-Induced Neurodevelopmental Impairments in the Progeny.

    PubMed

    Min, Hui; Dong, Jing; Wang, Yi; Wang, Yuan; Teng, Weiping; Xi, Qi; Chen, Jie

    2016-04-01

    Maternal hypothyroxinemia can induce neurodevelopmental impairments in the developing fetus. We here review recent studies on the epidemiology and molecular mechanisms associated with this important public health issue. In 2011, the American Thyroid Association defined maternal hypothyroxinemia as low serum free thyroxine (FT4) levels (<5th or <10th percentile) existing in conjunction with normal serum free triiodothyronine (FT3) or thyroid stimulating hormone (TSH) levels during pregnancy. Compared to clinical or subclinical hypothyroidism, hypothyroxinemia is more commonly found in pregnant women. Hypothyroxinemia usually ensues in response to several factors, such as mild iodine deficiency, environmental endocrine disrupters, or certain thyroid diseases. Unequivocal evidence demonstrates that maternal hypothyroxinemia leads to negative effects on fetal brain development, increasing the risks for cognitive deficits and poor psychomotor development in resulting progeny. In support of this, rodent models provide direct evidence of neurodevelopmental damage induced by maternal hypothyroxinemia, including dendritic and axonal growth limitation, neural abnormal location, and synaptic function alteration. The neurodevelopmental impairments induced by hypothyroxinemia suggest an independent role of T4. Increasing evidence indicates that adequate thyroxine is required for the mothers in order to protect against the abnormal brain development in their progeny. PMID:25666160

  3. STRENGTHENING THE REFLECTIVE FUNCTIONING CAPACITIES OF PARENTS WHO HAVE A CHILD WITH A NEURODEVELOPMENTAL DISABILITY THROUGH A BRIEF, RELATIONSHIP-FOCUSED INTERVENTION.

    PubMed

    Sealy, Julie; Glovinsky, Ira P

    2016-01-01

    This randomized controlled trial examined the reflective functioning capacities of caregivers who have a child with a neurodevelopmental disorder between the ages of 2 years 0 months and 6 years 11 months. Children with a neurodevelopmental disorder receive a range of diagnoses, including sutism; however, they all exhibit social communication challenges that can derail social relationships. Forty parent-child dyads in Barbados were randomly assigned to either a developmental individual-difference, relationship-based/floortime(DIR/FT) group (n = 20), or a psychoeducational (wait-list) group (n = 20) with parental reflective functioning measured before and after a 12-week DIR/FT treatment intervention. Results revealed significant gains in parental reflective functioning in the treatment group, as compared to the psychoeducational (wait-list) group, after the 12-week relationship-focused intervention. PMID:26891621

  4. Social (pragmatic) communication disorders and autism spectrum disorder.

    PubMed

    Baird, Gillian; Norbury, Courtenay Frazier

    2016-08-01

    Changes have been made to the diagnostic criteria for autism spectrum disorder (ASD) in the recent revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and similar changes are likely in the WHO International Classification of Diseases (ICD-11) due in 2017. In light of these changes, a new clinical disorder, social (pragmatic) communication disorder (SPCD), was added to the neurodevelopmental disorders section of DSM-5. This article describes the key features of ASD, SPCD and the draft ICD-11 approach to pragmatic language impairment, highlighting points of overlap between the disorders and criteria for differential diagnosis. PMID:26699538

  5. Effectiveness of ignition interlocks for preventing alcohol-impaired driving and alcohol-related crashes: a Community Guide systematic review.

    PubMed

    Elder, Randy W; Voas, Robert; Beirness, Doug; Shults, Ruth A; Sleet, David A; Nichols, James L; Compton, Richard

    2011-03-01

    A systematic review of the literature to assess the effectiveness of ignition interlocks for reducing alcohol-impaired driving and alcohol-related crashes was conducted for the Guide to Community Preventive Services (Community Guide). Because one of the primary research issues of interest--the degree to which the installation of interlocks in offenders' vehicles reduces alcohol-impaired driving in comparison to alternative sanctions (primarily license suspension)--was addressed by a 2004 systematic review conducted for the Cochrane Collaboration, the current review incorporates that previous work and extends it to include more recent literature and crash outcomes. The body of evidence evaluated includes the 11 studies from the prior review, plus four more recent studies published through December 2007. The installation of ignition interlocks was associated consistently with large reductions in re-arrest rates for alcohol-impaired driving within both the earlier and later bodies of evidence. Following removal of interlocks, re-arrest rates reverted to levels similar to those for comparison groups. The limited available evidence from three studies that evaluated crash rates suggests that alcohol-related crashes decrease while interlocks are installed in vehicles. According to Community Guide rules of evidence, these findings provide strong evidence that interlocks, while they are in use in offenders' vehicles, are effective in reducing re-arrest rates. However, the potential for interlock programs to reduce alcohol-related crashes is currently limited by the small proportion of offenders who participate in the programs and the lack of a persistent beneficial effect once the interlock is removed. Suggestions for facilitating more widespread and sustained use of ignition interlocks are provided. PMID:21335270

  6. All-Wales licensed premises intervention (AWLPI): a randomised controlled trial to reduce alcohol-related violence

    PubMed Central

    2014-01-01

    Background Alcohol-related violence in and in the vicinity of licensed premises continues to place a considerable burden on the United Kingdom’s (UK) health services. Robust interventions targeted at licensed premises are therefore required to reduce the costs of alcohol-related harm. Previous evaluations of interventions in licensed premises have a number of methodological limitations and none have been conducted in the UK. The aim of the trial was to determine the effectiveness of the Safety Management in Licensed Environments intervention designed to reduce alcohol-related violence in licensed premises, delivered by Environmental Health Officers, under their statutory authority to intervene in cases of violence in the workplace. Methods/Design A national randomised controlled trial, with licensed premises as the unit of allocation. Premises were identified from all 22 Local Authorities in Wales. Eligible premises were those with identifiable violent incidents on premises, using police recorded violence data. Premises were allocated to intervention or control by optimally balancing by Environmental Health Officer capacity in each Local Authority, number of violent incidents in the 12 months leading up to the start of the project and opening hours. The primary outcome measure is the difference in frequency of violence between intervention and control premises over a 12 month follow-up period, based on a recurrent event model. The trial incorporates an embedded process evaluation to assess intervention implementation, fidelity, reach and reception, and to interpret outcome effects, as well as investigate its economic impact. Discussion The results of the trial will be applicable to all statutory authorities directly involved with managing violence in the night time economy and will provide the first formal test of Health and Safety policy in this environment. If successful, opportunities for replication and generalisation will be considered. Trial registration

  7. Personality and alcohol-related outcomes among mandated college students: descriptive norms, injunctive norms, and college-related alcohol beliefs as mediators.

    PubMed

    Pearson, Matthew R; Hustad, John T P

    2014-05-01

    The present study examined three alcohol-perception variables (descriptive norms, injunctive norms, and college-related alcohol beliefs) as mediators of the predictive effects of four personality traits (impulsivity, sensation seeking, anxiety sensitivity, and hopelessness) on alcohol use and alcohol-related consequences in a sample of mandated college students (n=875). Our findings replicated several findings of a previous study of incoming freshman college students (Hustad et al., in press) in that impulsivity and hopelessness had direct effects on alcohol-related problems, sensation seeking and impulsivity had indirect effects on alcohol-related outcomes via college-related alcohol beliefs, and college-related alcohol beliefs predicted both alcohol use and alcohol-related problems. We discuss the implications of our findings for global college student interventions as well as personality-targeted interventions. PMID:24589869

  8. Protective behavioral strategies, alcohol consumption, and negative alcohol-related consequences: do race and gender moderate these associations?

    PubMed

    Madson, Michael B; Zeigler-Hill, Virgil

    2013-01-01

    White, non-Hispanic college students tend to drink more alcohol and experience more negative consequences than African American college students. However, racial differences have not been examined for protective behavioral strategies. This study examined whether race and gender moderated the associations that protective behavioral strategies had with alcohol consumption and negative alcohol-related consequences. In general, the use of protective behavioral strategies were associated with greater deceases in consumption, harmful drinking, and negative consequences for White, non-Hispanic students than African American students, which suggests important racial differences related to protective strategy use. Research and clinical implications are provided. PMID:23967885

  9. Alcohol-related injury among Greek-letter college students: Defining a target population for secondary prevention

    PubMed Central

    O’Brien, Mary Claire; McNamara, Robert S; McCoy, Thomas P; Sutfin, Erin L; Wolfson, Mark; Rhodes, Scott D

    2013-01-01

    Members of Greek-letter societies are the heaviest drinkers on college campuses, and experience more alcohol-related problems than their peers. This study reports the results of a web-based survey administered to stratified random samples of college students from ten North Carolina universities. Greek-letter status was a significant independent risk factor for increased injury (both experienced and caused to others), even after adjusting for drinking behaviors. Prevention, screening, and intervention strategies are discussed in the context of these results. PMID:22689586

  10. Factors Associated With General and Sexual Alcohol-Related Consequences: An Examination of College Students Studying Abroad.

    PubMed

    Hummer, Justin F; Pedersen, Eric R; Mirza, Tehniat; Labrie, Joseph W

    2010-12-01

    This study contributes to the scarce research on U.S. college students studying abroad by documenting general and sexual negative alcohol-related risks and factors associated with such risk. The manner of drinking (quantity vs. frequency), predeparture expectations surrounding alcohol use while abroad, culture-related social anxiety, and perceived disparity between home and host cultures differentially predicted consequences abroad. The findings include important implications for student affairs professionals in developing study abroad-specific interventions and resources to maintain student well-being while abroad. PMID:23505594

  11. Effects of AlcoholEdu for College on Alcohol-Related Problems Among Freshmen: A Randomized Multicampus Trial*

    PubMed Central

    Paschall, Mallie J.; Antin, Tamar; Ringwalt, Christopher L.; Saltz, Robert F.

    2011-01-01

    Objective: AlcoholEdu for College is a 2- to 3-hour online course for incoming college freshmen. This study was the first multicampus trial to examine effects of AlcoholEdu for College on alcohol-related problems among freshmen. Method: Thirty universi participated in the study. Fifteen were randomly assigned to receive AlcoholEdu, and the other 15 were assigned to the control condition. AlcoholEdu was implemented by intervention schools during the summer and/or fall semester. Cross-sectional surveys of freshmen were conducted at each university beginning before the intervention in spring 2008/2009; post-intervention surveys were administered in fall 2008/2009 and spring 2009/2010. The surveys included questions about the past-30-day frequency of 28 alcohol-related problems, from which we created indices for the total number of problems and problems in seven domains: physiological, academic, social, driving under the influence/riding with drinking drivers, aggression, sexual risk taking, and victimization. Multilevel Poisson regression analyses were conducted to examine intent-to-treat and dosage effects of AlcoholEdu for College on these outcomes. Results: Multilevel intent-to-treat analyses indicated significant reductions in the risk for past-30-day alcohol problems in general and problems in the physiological, social, and victimization domains during the fall semester immediately after completion of the course. However, these effects did not persist in the spring semester. Additional analyses suggested stronger AlcoholEdu effects on these outcomes at colleges with higher rates of student course completion. No AlcoholEdu effects were observed for alcohol-related problems in the other four domains. Conclusions: AlcoholEdu for College appears to have beneficial short-term effects on victimization and the most common types of alcohol-related problems among freshmen. Universities may benefit the most by mandating AlcoholEdu for College for all incoming freshmen and

  12. The relationship between collective self-esteem, acculturation, and alcohol-related consequences among Asian American young adults.

    PubMed

    Pedersen, Eric R; Hsu, Sharon Hsin; Neighbors, Clayton; Lee, Christine M; Larimer, Mary E

    2013-01-01

    We examined the relationship between collective self-esteem (i.e., the value one places on being part of a collective group), acculturation, and alcohol-related consequences in a sample of 442 Asian American young adults. We found that membership self-esteem and public collective self-esteem interacted with acculturation such that low levels of both predicted greater rates of consequences. Participants with lower acculturation and greater private collective self-esteem experienced more alcohol consequences. This study suggests that differential aspects of collective self-esteem may serve as protective or risk factors for Asian American young adults depending on degree of acculturation. PMID:23480211

  13. The Relationship Between Collective Self-Esteem, Acculturation, and Alcohol-Related Consequences Among Asian American Young Adults

    PubMed Central

    PEDERSEN, ERIC R.; HSU, SHARON HSIN; NEIGHBORS, CLAYTON; LEE, CHRISTINE M.; LARIMER, MARY E.

    2016-01-01

    We examined the relationship between collective self-esteem (i.e., the value one places on being part of a collective group), acculturation, and alcohol-related consequences in a sample of 442 Asian American young adults. We found that membership self-esteem and public collective self-esteem interacted with acculturation such that low levels of both predicted greater rates of consequences. Participants with lower acculturation and greater private collective self-esteem experienced more alcohol consequences. This study suggests that differential aspects of collective self-esteem may serve as protective or risk factors for Asian American young adults depending on degree of acculturation. PMID:23480211

  14. Trends in binge and heavy drinking, alcohol-related problems, and combat exposure in the U.S. military.

    PubMed

    Bray, Robert M; Brown, Janice M; Williams, Jason

    2013-07-01

    Population-based Department of Defense health behavior surveys were examined for binge and heavy drinking among U.S. active duty personnel. From 1998-2008, personnel showed significant increases in heavy drinking (15% to 20%) and binge drinking (35% to 47%). The rate of alcohol-related serious consequences was 4% for nonbinge drinkers, 9% for binge drinkers, and 19% for heavy drinkers. Personnel with high combat exposure had significantly higher rates of heavy (26.8%) and binge (54.8%) drinking than their counterparts (17% and 45%, respectively). Heavy and binge drinking put service members at high risk for problems that diminish force readiness and psychological fitness. PMID:23869454

  15. Long-Term Neurodevelopmental Outcome of Monochorionic and Matched Dichorionic Twins

    PubMed Central

    Hack, Karien E. A.; Koopman-Esseboom, Corine; Derks, Jan B.; Elias, Sjoerd G.; de Kleine, Martin J. K.; Baerts, Wim; Go, Attie T. J. I.; Schaap, Arty H. P.; van der Hoeven, Mark A. H. B. M.; Eggink, Alex J.; Sollie, Krystyna M.; Weisglas-Kuperus, Nynke; A.Visser, Gerard H.

    2009-01-01

    Background Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years. Methods This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. Findings Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5–38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0–1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co

  16. Self and partner alcohol-related problems among ACOAs and non-ACOAs: associations with depressive symptoms and motivations for alcohol use.

    PubMed

    Kelley, Michelle L; Linden, Ashley N; Milletich, Robert J; Lau-Barraco, Cathy; Kurtz, Erin D; D'Lima, Gabrielle M; Bodkins, Jessica A; Sheehan, Brynn E

    2014-01-01

    The present study examined whether drinking motivations and depressive symptoms would have a stronger impact on alcohol-related problems among adult children of alcoholics (ACOAs) and their dating partners as compared to non-ACOAs and their dating partners. Participants were 197 undergraduate (60 ACOAs, 137 non-ACOAs) 18 to 25year-old female drinkers in dating relationships. Participants completed measures of ACOA screening, depressive symptoms, and drinking motives, as well as alcohol-related problems for themselves and their partner. Although no differences were found between ACOA and non-ACOA women's alcohol-related problems, ACOA women and women with greater depressive symptoms were at a higher risk of having a partner with more alcohol-related problems. In addition, we found that regardless of parental history of alcoholism, higher depressive symptoms coupled with stronger motives for drinking to cope with stressors predicted participants' own alcohol-related problems. These findings demonstrate the need for future research to examine additional factors that may moderate the effects of depressive symptoms and ACOA status on female college student drinking problems. A greater understanding of the unique and interactive effects of these variables on alcohol-related problems in both young women and their dating partners can aid in the development of prevention programs more targeted to the specific vulnerabilities of this population. PMID:24182750

  17. Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation.

    PubMed

    Das, R K; Lawn, W; Kamboj, S K

    2015-01-01

    The transient period of memory instability that can be triggered when memories are retrieved under certain conditions offers an opportunity to modify the maladaptive memories at the heart of substance use disorders (SUDs). However, very well-learned memories (such as those in excessive drinking and alcohol use disorders) are resistant to destabilisation when retrieved or may not destabilise at all. Memory retrieval and intervention procedures that reliably destabilise and update maladaptive motivational memories may help to improve the long-term treatment of SUDs. In 59 hazardous drinkers, we tested a novel retrieval procedure for destabilising well-learned cue-drinking memory networks that maximises prediction error (PE) via guided expectancy violation during retrieval of these memories. This was compared with a retrieval procedure without PE and no-retrieval controls. We subsequently counterconditioned alcohol cues with disgusting tastes and images in all groups and assessed responding to alcohol stimuli 1 week later. Counterconditioning following PE retrieval produced generalised reductions in oculomotor attentional bias, explicit valuation and outcome expectancies in response to alcohol cues 1 week after intervention, evidence of updating of distributed motivational drinking memory networks. These findings demonstrate that well-learned cue-drinking memories can be destabilised and that learning history need not constrain memory destabilisation if PE is maximised at retrieval. Broad rewriting of diverse aspects of maladaptive memory by counterconditioning is achievable following this procedure. The procedure described may provide a platform for the development of novel memory-modifying interventions for SUDs. PMID:26393491

  18. Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine.

    PubMed

    Wells, Peter G; Bhatia, Shama; Drake, Danielle M; Miller-Pinsler, Lutfiya

    2016-06-01

    In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108-130, 2016. © 2016 Wiley Periodicals, Inc. PMID:27345013

  19. Reducing alcohol-related aggression: Effects of a self-awareness manipulation and locus of control in heavy drinking males.

    PubMed

    Purvis, Danielle M; Gallagher, Kathryn E; Parrott, Dominic J

    2016-07-01

    Alcohol Myopia Theory (AMT; Steele & Josephs, 1990) purports that alcohol facilitates aggression by narrowing attentional focus onto salient and instigatory cues common to conflict situations. However, few tests of its counterintuitive prediction - that alcohol may decrease aggression when inhibitory cues are most salient - have been conducted. The present study examined whether an AMT-inspired self-awareness intervention manipulation would reduce heavy drinking men's intoxicated aggression toward women and also examined whether a relevant individual variable, locus of control, would moderate this effect. Participants were 102 intoxicated male heavy drinkers who completed a self-report measure of locus of control and completed the Taylor Aggression Paradigm (Taylor, 1967). In this task, participants administered electric shocks to, and received electric shocks from, a fictitious female opponent while exposed to an environment saturated with or devoid of self-awareness cues. Results indicated that the self-awareness manipulation was associated with less alcohol-related aggression toward the female confederate for men who reported an internal, but not an external, locus of control. Findings support AMT as a theoretical framework to inform preventative interventions for alcohol-related aggression and highlight the importance of individual differences in receptivity to such interventions. PMID:26905761

  20. Developing a guide for community-based groups to reduce alcohol-related harm among African migrants.

    PubMed

    Jaworski, Alison; Brown, Tony; Norman, Catherine; Hata, Kiri; Toohey, Mark; Vasiljevic, Dubravka; Rowe, Rachel

    2016-04-01

    Issue addressed Alcohol-related harm is an issue of concern for African migrant communities living in Australia. However, there has been little information available to guide workers in developing culturally sensitive health promotion strategies. Methods A three-step approach, comprising a literature review, community consultations and an external review, was undertaken to develop a guide to assist organisations and health promotion groups working with African migrant communities to address alcohol-related harms. Discussion There was a high level of agreement between the three steps. Addressing alcohol harms with African migrant communities requires approaches that are sensitive to the needs, structures and experiences of communities. The process should incorporate targeted approaches that enable communities to achieve their resettlement goals as well as strengthening mainstream health promotion efforts. Conclusions The resource produced guides alcohol harm prevention coalitions and workers from the first steps of understanding the influences of acculturation and resettlement on alcohol consumption, through to planning, developing and evaluating an intervention in partnership with communities. So what? This paper advances knowledge by providing a precise summary of Australian African migrant focused alcohol and other drug research to date. It also describes a three-step approach that aimed to incorporate a diversity of community views in the creation of a health promotion and community capacity-building resource. PMID:26726816