Bile Acids in Neurodegenerative Disorders

PubMed Central

Ackerman, Hayley D.; Gerhard, Glenn S.

2016-01-01

Bile acids, a structurally related group of molecules derived from cholesterol, have a long history as therapeutic agents in medicine, from treatment for primarily ocular diseases in ancient Chinese medicine to modern day use as approved drugs for certain liver diseases. Despite evidence supporting a neuroprotective role in a diverse spectrum of age-related neurodegenerative disorders, including several small pilot clinical trials, little is known about their molecular mechanisms or their physiological roles in the nervous system. We review the data reported for their use as treatments for neurodegenerative diseases and their underlying molecular basis. While data from cellular and animal models and clinical trials support potential efficacy to treat a variety of neurodegenerative disorders, the relevant bile acids, their origin, and the precise molecular mechanism(s) by which they confer neuroprotection are not known delaying translation to the clinical setting. PMID:27920719

Pre-adult versus adult onset major depressive disorder in a naturalistic patient sample: the Leiden Routine Outcome Monitoring Study.

PubMed

van Noorden, M S; Minkenberg, S E; Giltay, E J; den Hollander-Gijsman, M E; van Rood, Y R; van der Wee, N J; Zitman, F G

2011-07-01

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients. Altogether, 1552 out-patients, mean age 39.2 ± 11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender. Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26-2.60) in patients with pre-adult versus adult onset MDD. Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Recent Patent Advances for Neurodegenerative Disorders and its Treatment.

PubMed

Kumar, Bhavna; Sharma, Deepika

2017-01-01

Neurodegenerative disorders are among the most common challenging diseases that affect the population with extreme medical and financial burdens. Widely seen neurodegeneration affects population of all ages, as it progresses with age, affecting a large proportion of elderly population including patients, caregivers, and immensely increasing the financial load of the country. These diseases have a very complex nature that frequently results from combined genetic, environmental and pathological factors. Various challenges are faced by the researchers working on the pathogenesis and the possible treatment of neurodegenerative disorder. The review has analysed for recent patent documents and treatment approaches for neurodegenerative disorders. This review does not relate to potential targets such as ( i.e. protein where modulation could be predicted to impact on pathophysiology), rather it mainly focuses on various available patented approaches for neurodegenerative disorders. The study design is based on updating the international and national literatures and an exhaustive patent search, compiling various patented documents for the treatment of neurodegenerative disorders (EP2282779A1, US20110229555A1) to provide information in the state of technological innovation in terms of research and development. In the present review, the authors described various neurodegenerative diseases, there treatment strategies and emphasized on various patented approaches for age-related neurodegenerative disorders such as novel therapeutic methods for treating Alzheimer's and associated disorders via modulated cell stress response EP2282779A1, through combined therapies that modulate angiogenesis US20120058992A1. The review will attract the interest of academics, researchers, students and pharmaceutical companies with regard to the recent on-going activities in neurodegenerative disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

PubMed

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

Comparative Incidence of Conformational, Neurodegenerative Disorders

PubMed Central

de Pedro-Cuesta, Jesús; Rábano, Alberto; Martínez-Martín, Pablo; Ruiz-Tovar, María; Alcalde-Cabero, Enrique; Almazán-Isla, Javier; Avellanal, Fuencisla; Calero, Miguel

2015-01-01

Background The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs). Methods We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD). We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD) forms, amyotrophic lateral sclerosis (ALS), and sporadic rapidly progressing neurodegenerative dementia (sRPNDd). For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined. Findings Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD), to 1589 and 2589 for AMD and Alzheimer's disease (AD) respectively. Age-specific profiles varied from (a) symmetrical, inverted V-shaped curves for low incidences to (b) those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c) a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20–24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration. Interpretation These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to

Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Swati; Yadav, Anuradha; Academy of Scientific and Innovative Research

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found thatmore » the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models. - Highlights: • Peroxisome -activated receptors (PPARs) serve to be a promising therapeutic target for several neurodegenerative disorders. • PPAR agonist as well as provides neuroprotection in vitro as well as in vivo animal models of neurodegenerative disorders. • PPAR activating anti-inflammatory drugs use is effective in decreasing progression of neurodegenerative diseases.« less

Aquatherapy for neurodegenerative disorders.

PubMed

Plecash, Alyson R; Leavitt, Blair R

2014-01-01

Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders.

Impacts of age of onset of substance use disorders on risk of adult incarceration among disadvantaged urban youth: a propensity score matching approach.

PubMed

Slade, Eric P; Stuart, Elizabeth A; Salkever, David S; Karakus, Mustafa; Green, Kerry M; Ialongo, Nicholas

2008-05-01

Age of onset of substance use disorders in adolescence and early adulthood could be associated with higher rates of adult criminal incarceration in the U.S., but evidence of these associations is scarce. Propensity score matching was used to estimate the association between adolescent-onset substance use disorders and the rate of incarceration, as well as incarceration costs and self-reported criminal arrests and convictions, of young men predominantly from African American, lower income, urban households. Age of onset was differentiated by whether onset of the first disorder occurred by age 16. Onset of a substance use disorder by age 16, but not later onset, was associated with a fourfold greater risk of adult incarceration for substance related offenses as compared to no disorder (0.35 vs. 0.09, P=0.044). Onset by age 16 and later onset were both positively associated with incarceration costs and risk of arrest and conviction, though associations with crime outcomes were more consistent with respect to onset by age 16. Results were robust to propensity score adjustment for observable predictors of substance use in adolescence and involvement in crime as an adult. Among young men in this high risk minority sample, having a substance use disorder by age 16 was associated with higher risk of incarceration for substance related offenses in early adulthood and with more extensive criminal justice system involvement as compared to having no disorder or having a disorder beginning at a later age.

The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration

PubMed Central

2013-01-01

Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional. This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseasesis largely unclear. In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca2+) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration. PMID:23829673

Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability

ERIC Educational Resources Information Center

Baker, Emma K.; Richdale, Amanda L.; Hazi, Agnes; Prendergast, Luke A.

2017-01-01

This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression…

Adult-onset offenders: Is a tailored theory warranted?

PubMed Central

Beckley, Amber L.; Caspi, Avshalom; Harrington, Honalee; Houts, Renate M.; Mcgee, Tara Renae; Morgan, Nick; Schroeder, Felix; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Purpose To describe official adult-onset offenders, investigate their antisocial histories and test hypotheses about their origins. Methods We defined adult-onset offenders among 931 Dunedin Study members followed to age 38, using criminal-court conviction records. Results Official adult-onset offenders were 14% of men, and 32% of convicted men, but accounted for only 15% of convictions. As anticipated by developmental theories emphasizing early-life influences on crime, adult-onset offenders’ histories of antisocial behavior spanned back to childhood. Relative to juvenile-offenders, during adolescence they had fewer delinquent peers and were more socially inhibited, which may have protected them from conviction. As anticipated by theories emphasizing the importance of situational influences on offending, adult-onset offenders, relative to non-offenders, during adulthood more often had schizophrenia, bipolar disorder, and alcohol-dependence, had weaker social bonds, anticipated fewer informal sanctions, and self-reported more offenses. Contrary to some expectations, adult-onset offenders did not have high IQ or high socioeconomic-status families protecting them from juvenile conviction. Conclusions A tailored theory for adult-onset offenders is unwarranted because few people begin crime de novo as adults. Official adult-onset offenders fall on a continuum of crime and its correlates, between official non-offenders and official juvenile-onset offenders. Existing theories can accommodate adult-onset offenders. PMID:27134318

Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

PubMed

Miyake, Noriko; Fukai, Ryoko; Ohba, Chihiro; Chihara, Takahiro; Miura, Masayuki; Shimizu, Hiroshi; Kakita, Akiyoshi; Imagawa, Eri; Shiina, Masaaki; Ogata, Kazuhiro; Okuno-Yuguchi, Jiu; Fueki, Noboru; Ogiso, Yoshifumi; Suzumura, Hiroshi; Watabe, Yoshiyuki; Imataka, George; Leong, Huey Yin; Fattal-Valevski, Aviva; Kramer, Uri; Miyatake, Satoko; Kato, Mitsuhiro; Okamoto, Nobuhiko; Sato, Yoshinori; Mitsuhashi, Satomi; Nishino, Ichizo; Kaneko, Naofumi; Nishiyama, Akira; Tamura, Tomohiko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Tanaka, Fumiaki; Saitsu, Hirotomo; Matsumoto, Naomichi

2016-10-06

We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Childhood-compared to adolescent-onset bipolar disorder has more statistically significant clinical correlates.

PubMed

Holtzman, Jessica N; Miller, Shefali; Hooshmand, Farnaz; Wang, Po W; Chang, Kiki D; Hill, Shelley J; Rasgon, Natalie L; Ketter, Terence A

2015-07-01

The strengths and limitations of considering childhood-and adolescent-onset bipolar disorder (BD) separately versus together remain to be established. We assessed this issue. BD patients referred to the Stanford Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Patients with childhood- and adolescent-onset were compared to those with adult-onset for 7 unfavorable bipolar illness characteristics with replicated associations with early-onset patients. Among 502 BD outpatients, those with childhood- (<13 years, N=110) and adolescent- (13-18 years, N=218) onset had significantly higher rates for 4/7 unfavorable illness characteristics, including lifetime comorbid anxiety disorder, at least ten lifetime mood episodes, lifetime alcohol use disorder, and prior suicide attempt, than those with adult-onset (>18 years, N=174). Childhood- but not adolescent-onset BD patients also had significantly higher rates of first-degree relative with mood disorder, lifetime substance use disorder, and rapid cycling in the prior year. Patients with pooled childhood/adolescent - compared to adult-onset had significantly higher rates for 5/7 of these unfavorable illness characteristics, while patients with childhood- compared to adolescent-onset had significantly higher rates for 4/7 of these unfavorable illness characteristics. Caucasian, insured, suburban, low substance abuse, American specialty clinic-referred sample limits generalizability. Onset age is based on retrospective recall. Childhood- compared to adolescent-onset BD was more robustly related to unfavorable bipolar illness characteristics, so pooling these groups attenuated such relationships. Further study is warranted to determine the extent to which adolescent-onset BD represents an intermediate phenotype between childhood- and adult-onset BD. Copyright © 2015 Elsevier B.V. All rights reserved.

Associations between mental disorders and subsequent onset of hypertension

PubMed Central

Stein, Dan J.; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Bruffaerts, Ronny; de Jonge, Peter; Liu, Zharoui; Caldas-de-Almeida, Jose Miguel; O’Neill, Siobhan; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Mattias C.; Benjet, Corina; de Graaf, Ron; Ferry, Finola; Kovess-Masfety, Viviane; Levinson, Daphna; de Girolamo, Giovanni; Florescu, Silvia; Hu, Chiyi; Kawakami, Norito; Haro, Josep Maria; Piazza, Marina; Wojtyniak, Bogdan J; Xavier, Miguel; Lim, Carmen C.W.; Kessler, Ronald C.; Scott, Kate

2013-01-01

Background Previous work has suggested significant associations between various psychological symptoms (e.g. depression, anxiety, anger, alcohol abuse) and hypertension. However, the presence and extent of associations between common mental disorders and subsequent adult onset of hypertension remains unclear. Further, there is little data available on how such associations vary by gender or over life course. Methods Data from the World Mental Health Surveys (comprising 19 countries, and 52,095 adults) were used. Survival analyses estimated associations between first onset of common mental disorders and subsequent onset of hypertension, with and without psychiatric comorbidity adjustment. Variations in the strength of associations by gender and by life course stage of onset of both the mental disorder and hypertension were investigated. Results After psychiatric comorbidity adjustment, depression, panic disorder, social phobia, specific phobia, binge eating disorder, bulimia nervosa, alcohol abuse, and drug abuse were significantly associated with subsequent diagnosis of hypertension (with ORs ranging from 1.1 to 1.6). Number of lifetime mental disorders was associated with subsequent hypertension in a dose-response fashion. For social phobia and alcohol abuse, associations with hypertension were stronger for males than females. For panic disorder, the association with hypertension was particularly apparent in earlier onset hypertension. Conclusions Depression, anxiety, impulsive eating disorders, and substance use disorders disorders were significantly associated with the subsequent diagnosis of hypertension. These data underscore the importance of early detection of mental disorders, and of physical health monitoring in people with these conditions.. PMID:24342112

Unusual early-onset Huntingtons disease.

PubMed

Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

2003-06-01

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

ERIC Educational Resources Information Center

Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

2006-01-01

Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

Cannabidiol: a promising drug for neurodegenerative disorders?

PubMed

Iuvone, Teresa; Esposito, Giuseppe; De Filippis, Daniele; Scuderi, Caterina; Steardo, Luca

2009-01-01

Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective. In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

PubMed Central

Liao, Yajin; Dong, Yuan; Cheng, Jinbo

2017-01-01

The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

Developmental evaluation of family functioning deficits in youths and young adults with childhood-onset bipolar disorder.

PubMed

MacPherson, Heather A; Ruggieri, Amanda L; Christensen, Rachel E; Schettini, Elana; Kim, Kerri L; Thomas, Sarah A; Dickstein, Daniel P

2018-08-01

Childhood-onset bipolar disorder (BD) is a serious condition that affects the patient and family. While research has documented familial dysfunction in individuals with BD, no studies have compared developmental differences in family functioning in youths with BD vs. adults with prospectively verified childhood-onset BD. The Family Assessment Device (FAD) was used to examine family functioning in participants with childhood-onset BD (n = 116) vs. healthy controls (HCs) (n = 108), ages 7-30 years, using multivariate analysis of covariance and multiple linear regression. Participants with BD had significantly worse family functioning in all domains (problem solving, communication, roles, affective responsiveness, affective involvement, behavior control, general functioning) compared to HCs, regardless of age, IQ, and socioeconomic status. Post-hoc analyses suggested no influence for mood state, global functioning, comorbidity, and most medications, despite youths with BD presenting with greater severity in these areas than adults. Post-hoc tests eliminating participants taking lithium (n = 17) showed a significant diagnosis-by-age interaction: youths with BD had worse family problem solving and communication relative to HCs. Limitations include the cross-sectional design, clinical differences in youths vs. adults with BD, ambiguity in FAD instructions, participant-only report of family functioning, and lack of data on psychosocial treatments. Familial dysfunction is common in childhood-onset BD and endures into adulthood. Early identification and treatment of both individual and family impairments is crucial. Further investigation into multi-level, family-based mechanisms underlying childhood-onset BD may clarify the role family factors play in the disorder, and offer avenues for the development of novel, family-focused therapeutic strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Late-onset ADHD in adults: milder, but still dysfunctional.

PubMed

Karam, Rafael G; Bau, Claiton H D; Salgado, Carlos A I; Kalil, Katiane L S; Victor, Marcelo M; Sousa, Nyvia O; Vitola, Eduardo S; Picon, Felipe A; Zeni, Gregory D; Rohde, Luis A; Belmonte-de-Abreu, Paulo; Grevet, Eugenio H

2009-04-01

The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria - AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients. The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models. Late-onset subjects were diagnosed later (P=0.04), had a lower frequency of problems with authority and discipline (P=0.004), and lower scores in SNAP-IV (P<0.001) and in Barkley's scale for problems in areas of life activities (P=0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) (P=0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics. This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.

Molecular diagnostics of neurodegenerative disorders.

PubMed

Agrawal, Megha; Biswas, Abhijit

2015-01-01

Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

Modifiers and mechanisms of multi-system polyglutamine neurodegenerative disorders: lessons from fly models.

PubMed

Mallik, Moushami; Lakhotia, Subhash C

2010-12-01

Polyglutamine (polyQ) diseases, resulting from a dynamic expansion of glutamine repeats in a polypeptide, are a class of genetically inherited late onset neurodegenerative disorders which, despite expression of the mutated gene widely in brain and other tissues, affect defined subpopulations of neurons in a disease-specific manner. We briefly review the different polyQ-expansion-induced neurodegenerative disorders and the advantages of modelling them in Drosophila. Studies using the fly models have successfully identified a variety of genetic modifiers and have helped in understanding some of the molecular events that follow expression of the abnormal polyQ proteins. Expression of the mutant polyQ proteins causes, as a consequence of intra-cellular and inter-cellular networking, mis-regulation at multiple steps like transcriptional and posttranscriptional regulations, cell signalling, protein quality control systems (protein folding and degradation networks), axonal transport machinery etc., in the sensitive neurons, resulting ultimately in their death. The diversity of genetic modifiers of polyQ toxicity identified through extensive genetic screens in fly and other models clearly reflects a complex network effect of the presence of the mutated protein. Such network effects pose a major challenge for therapeutic applications.

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

PubMed Central

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

PubMed

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

Tsallis statistics and neurodegenerative disorders

NASA Astrophysics Data System (ADS)

Iliopoulos, Aggelos C.; Tsolaki, Magdalini; Aifantis, Elias C.

2016-08-01

In this paper, we perform statistical analysis of time series deriving from four neurodegenerative disorders, namely epilepsy, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD). The time series are concerned with electroencephalograms (EEGs) of healthy and epileptic states, as well as gait dynamics (in particular stride intervals) of the ALS, PD and HDs. We study data concerning one subject for each neurodegenerative disorder and one healthy control. The analysis is based on Tsallis non-extensive statistical mechanics and in particular on the estimation of Tsallis q-triplet, namely {qstat, qsen, qrel}. The deviation of Tsallis q-triplet from unity indicates non-Gaussian statistics and long-range dependencies for all time series considered. In addition, the results reveal the efficiency of Tsallis statistics in capturing differences in brain dynamics between healthy and epileptic states, as well as differences between ALS, PD, HDs from healthy control subjects. The results indicate that estimations of Tsallis q-indices could be used as possible biomarkers, along with others, for improving classification and prediction of epileptic seizures, as well as for studying the gait complex dynamics of various diseases providing new insights into severity, medications and fall risk, improving therapeutic interventions.

Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

PubMed

Liu, Ying; Deng, Wenbin

2016-05-01

With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features.

PubMed

Robakis, Daphne

2017-01-01

Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features

PubMed Central

Robakis, Daphne

2017-01-01

Background Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Methods Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. Results The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. Discussion We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder. PMID:28546883

Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

PubMed

Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

2017-03-01

Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

The relationship between childhood conduct disorder and adult antisocial behavior is partially mediated by early-onset alcohol abuse.

PubMed

Khalifa, Najat; Duggan, Conor; Howard, Rick; Lumsden, John

2012-10-01

Early-onset alcohol abuse (EOAA) was previously found to both mediate and moderate the effect of childhood conduct disorder (CD) on adult antisocial behavior (ASB) in an American community sample of young adults (Howard, R., Finn, P. R., Gallagher, J., & Jose, P. (2011). Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behavior. Journal of Forensic Psychiatry and Psychology. Advance online publication. doi:10.1080/14789949.2011.641996). This study tested whether this result would generalize to a British forensic sample comprising 100 male forensic patients with confirmed personality disorder. Results confirmed that those in whom EOAA co-occurred with CD showed the highest level of personality pathology, particularly Cluster B traits and antisocial/borderline comorbidity. Those with co-occurring CD with EOAA, compared with those showing only CD, showed more violence in their criminal history and greater recreational drug use. Regression analysis showed that both EOAA and CD predicted adult ASB when covariates were controlled. Further analysis showed that EOAA significantly mediated but did not moderate the effect of CD on ASB. The failure to demonstrate an exacerbating effect of EOAA on the relationship between CD and ASB likely reflects the high prevalence of CD in this forensic sample. Some implications of these findings are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Disorders of lysosomal acidification - the emerging role of v-ATPase in aging and neurodegenerative disease

PubMed Central

Colacurcio, Daniel J.; Nixon, Ralph A.

2016-01-01

Autophagy and endocytosis deliver unneeded cellular materials to lysosomes for degradation. Beyond processing cellular waste, lysosomes release metabolites and ions that serve signaling and nutrient sensing roles, linking the functions of the lysosome to various pathways for intracellular metabolism and nutrient homeostasis. Each of these lysosomal behaviors is influenced by the intraluminal pH of the lysosome, which is maintained in the low acidic range by a proton pump, the vacuolar ATPase (v-ATPase). New reports implicate altered v-ATPase activity and lysosomal pH dysregulation in cellular aging, longevity, and adult-onset neurodegenerative diseases, including forms of Parkinson Disease and Alzheimer Disease. Genetic defects of subunits composing the v-ATPase or v-ATPase-related proteins occur in an increasingly recognized group of familial neurodegenerative diseases. Here, we review the expanding roles of the v-ATPase complex as a platform regulating lysosomal proteolysis and cellular homeostasis. We discuss the unique vulnerability of neurons to persistent low level lysosomal dysfunction and review recent clinical and experimental studies that link dysfunction of the v-ATPase complex to neurodegenerative diseases across the age spectrum. PMID:27197071

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

PubMed Central

Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

2018-01-01

Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci

Global warming and neurodegenerative disorders: speculations on their linkage.

PubMed

Habibi, Laleh; Perry, George; Mahmoudi, Morteza

2014-01-01

Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

Predictive gene testing for Huntington disease and other neurodegenerative disorders.

PubMed

Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

2013-12-01

Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

PubMed

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Objective measures of sleep and dim light melatonin onset in adolescents and young adults with delayed sleep phase disorder compared to healthy controls.

PubMed

Saxvig, Ingvild W; Wilhelmsen-Langeland, Ane; Pallesen, Ståle; Vedaa, Oystein; Nordhus, Inger H; Sørensen, Eli; Bjorvatn, Bjørn

2013-08-01

Delayed sleep phase disorder is characterized by a delay in the timing of the major sleep period relative to conventional norms. The sleep period itself has traditionally been described as normal. Nevertheless, it is possible that sleep regulatory mechanism disturbances associated with the disorder may affect sleep duration and/or architecture. Polysomnographic data that may shed light on the issue are scarce. Hence, the aim of this study was to examine polysomnographic measures of sleep in adolescents and young adults with delayed sleep phase disorder, and to compare findings to that of healthy controls. A second aim was to estimate dim light melatonin onset as a marker of circadian rhythm and to investigate the phase angle relationship (time interval) between dim light melatonin onset and the sleep period. Data from 54 adolescents and young adults were analysed, 35 diagnosed with delayed sleep phase disorder and 19 healthy controls. Results show delayed timing of sleep in participants with delayed sleep phase disorder, but once sleep was initiated no group differences in sleep parameters were observed. Dim light melatonin onset was delayed in participants with delayed sleep phase disorder, but no difference in phase angle was observed between the groups. In conclusion, both sleep and dim light melatonin onset were delayed in participants with delayed sleep phase disorder. The sleep period appeared to occur at the same circadian phase in both groups, and once sleep was initiated no differences in sleep parameters were observed. © 2013 European Sleep Research Society.

Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland.

PubMed

Williams, L; McGovern, E; Kimmich, O; Molloy, A; Beiser, I; Butler, J S; Molloy, F; Logan, P; Healy, D G; Lynch, T; Walsh, R; Cassidy, L; Moriarty, P; Moore, H; McSwiney, T; Walsh, C; O'Riordan, S; Hutchinson, M

2017-01-01

Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4-19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician's dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder. © 2016 EAN.

New onset of idiopathic bilateral ear tics in an adult.

PubMed

Agrawal, Amit; Shrestha, Rabin

2009-04-01

Tic disorders are commonly considered to be childhood syndromes. Newly presenting tic disorders during adulthood are uncommon and mostly described in relation to an acquired brain lesion or as incidental tics, particularly in context with other neurological or psychiatric diseases. Tic disorder involving the ears is extremely uncommon with only few studies in English literature. In the present case, we describe an adult patient with new-onset idiopathic tics disorder involving both ears, causing social embarrassment. In addition, our patient had recent onset of the tics without any childhood or family history of tic disorders. The single most important component of management is an accurate diagnosis. At the same time, tics should be differentiated from other movement disorders such as chorea, stereotypy, and dystonias.

Age of onset of life-time mental disorders and treatment contact.

PubMed

Vaingankar, Janhavi Ajit; Rekhi, Gurpreet; Subramaniam, Mythily; Abdin, Edimansyah; Chong, Siow Ann

2013-05-01

Early onset of mental disorders is a major social and public health concern as it affects individuals in their most formative years. The impact is more pronounced when early onset is also associated with treatment delay. Little is known about the age of onset (AOO) for mental disorders and its predictors in Singapore. A national mental health survey was conducted among adult residents aged 18 years and above in Singapore. The composite international diagnostic interview (CIDI 3.0) was used to establish the life-time diagnosis of major depressive disorder (MDD), dysthymia, bipolar disorder, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol abuse and dependence, and the age of onset as well as any subsequent treatment contact. A total of 6,616 respondents (mean age of 43.9 years) participated in the survey giving a response rate of 75.9 %. The median AOO for having any one of the mental disorders was 22 years with variation among the different disorders. Predictors for AOO varied across the mental disorders. Only 8 % had sought any treatment in the first year after onset. Males, those belonging to Malay and Indian ethnicities and 50+ age cohorts were less likely to have made treatment contact in the year of onset. Nearly half of the respondents with any life-time mental disorder would have its onset by age of 22 years, and very few had sought treatment within the first year from onset. The study also identified socio-demographic predictors associated with AOO for mental disorders and delayed treatment contact, thus highlighting a vulnerable subpopulation that can be targeted for outreach and early interventions.

Sexual orientation versus age of onset as bases for typologies (subtypes) for gender identity disorder in adolescents and adults.

PubMed

Lawrence, Anne A

2010-04-01

The most widely used and influential typologies for transsexualism and gender identity disorder (GID) in adolescents and adults employ either sexual orientation or age of onset of GID-related symptoms as bases for categorization. This review compares these two typological approaches, with the goal of determining which one should be employed for the diagnosis of GID in Adolescents or Adults (or its successor diagnosis) in the forthcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Typologies based on sexual orientation and age of onset of GID-related symptoms are roughly comparable in ease and reliability of subtype assignment. Typologies based on sexual orientation, however, employ subtypes that are less ambiguous and better suited to objective confirmation and that offer more concise, comprehensive clinical description. Typologies based on sexual orientation are also superior in their ability to predict treatment-related outcomes and comorbid psychopathology and to facilitate research. Commonly expressed objections to typologies based on sexual orientation are unpersuasive when examined closely. The DSM should continue to employ subtypes based on sexual orientation for the diagnosis of GID in Adolescents or Adults or its successor diagnosis.

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Disturbed sleep as risk factor for the subsequent onset of bipolar disorder--Data from a 10-year prospective-longitudinal study among adolescents and young adults.

PubMed

Ritter, Philipp S; Höfler, Michael; Wittchen, Hans-Ulrich; Lieb, Roselind; Bauer, Michael; Pfennig, Andrea; Beesdo-Baum, Katja

2015-09-01

There is ample data suggesting that individuals with bipolar disorder more frequently suffer from disturbed sleep even when euthymic. Since sleep is a process that is crucial for affective homeostasis, disturbed sleep in healthy individuals may be a risk factor for the subsequent onset of bipolar disorder. Utilizing data from a large cohort of adolescents and young adults, this study tests the hypothesis that disturbed sleep constitutes a risk factor for the later onset of bipolar disorder. A representative community sample of N = 3021 adolescents and young adults (baseline age 14-24) was assessed using the standardized Composite International Diagnostic Interview and followed-up prospectively up to 3 times over up to 10 years. Disturbed sleep at baseline was quantified utilizing the corresponding items from the self-report inventory SCL-90-R. The compound value (insomnia-score) as an ordinal parameter for the severity of sleep disturbances was used to assess associations with the incidence of bipolar disorder among participants free of major mental disorder at baseline (N = 1943) using odds ratios (OR) from logistic regressions. Analyses were adjusted for age, gender, parental mood disorder and lifetime alcohol or cannabis dependence. Poor sleep quality significantly increased the risk for the subsequent development of bipolar disorder (OR = 1.75; p = 0.001). Regarding individual sleep items, trouble falling asleep and early morning awakening were predictive for the subsequent onset of bipolar disorder. Disturbed sleep in persons otherwise free of major mental disorders appears to confer an increased risk for the subsequent onset of bipolar disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emotional Processing in Male Adolescents with Childhood-Onset Conduct Disorder

ERIC Educational Resources Information Center

Herpertz, Sabine C.; Huebner, Thomas; Marx, Ivo; Vloet, Timo D.; Fink, Gereon R.; Stoecker, Tony; Shah, N. Jon; Konrad, Kerstin; Herpertz-Dahlmann, Beate

2008-01-01

Background: Boys with early onset of conduct disorder (CD), most of whom also meet diagnostic criteria of a comorbid attention deficit hyperactivity disorder (ADHD), tend to exhibit high levels of aggression throughout development. While a number of functional neuroimaging studies on emotional processing have been performed in antisocial adults,…

Ghrelin and Neurodegenerative Disorders-a Review.

PubMed

Shi, Limin; Du, Xixun; Jiang, Hong; Xie, Junxia

2017-03-01

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy.

HDL and Cognition in Neurodegenerative Disorders

PubMed Central

Hottman, David A.; Chernick, Dustin; Cheng, Shaowu; Wang, Zhe; Li, Ling

2014-01-01

High-density lipoproteins (HDL) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function. PMID:25131449

Adult attention deficit hyperactivity disorder in an anxiety disorders population.

PubMed

Van Ameringen, Michael; Mancini, Catherine; Simpson, William; Patterson, Beth

2011-08-01

Adult Attention Deficit Hyperactivity Disorder (ADHD) is a life-long, chronic disorder, which has its onset in childhood and is associated with significant functional impairment. ADHD appears to be highly comorbid with other psychiatric disorders, however, literature is lacking concerning ADHD/anxiety comorbidity. To that end, we examined the prevalence of ADHD in an anxiety disorder sample. Consecutive patients referred to an anxiety disorders clinic completed a variety of anxiety disorder self-report measures as well as the Adult ADHD self-report scale and were clinically assessed using the Structured Clinical Interview for DSM-IV, and the ADHD module of the Mini International Neuropsychiatric Interview. Of the 129 patients assessed, the rate of adult ADHD was 27.9%. The mean age of the sample was 33.1 ± 12.5 years, and the mean baseline CGI-S was 4.6 ± 1.1 (moderate to marked severity). The majority of the sample was female (63.6%) and single (49.5%). The most common comorbid disorders associated with ADHD were major depressive disorder (53.8%), social phobia (38.5%), generalized anxiety disorder (23.1%), and impulse control disorders (30.8%). Individuals with ADHD had higher symptom severity scores for obsessive-compulsive disorder, (P≤ 0.05) and for GAD (P≤ 0.05) and reported a significantly earlier age of onset for depression as compared to those without (P≤ 0.05). The prevalence of adult ADHD was higher in our anxiety disorders clinic sample than found in the general population. Clinical implications of these findings are discussed. © 2010 Blackwell Publishing Ltd.

Rest tremor in idiopathic adult-onset dystonia.

PubMed

Gigante, A F; Berardelli, A; Defazio, G

2016-05-01

Tremor in dystonia has been described as a postural or kinetic abnormality. In recent series, however, patients with idiopathic adult-onset dystonia also displayed rest tremor. The frequency and distribution of rest tremor were studied in a cohort of 173 consecutive Italian patients affected by various forms of idiopathic adult-onset dystonia attending our movement disorder clinic over 8 months. Examination revealed tremor in 59/173 patients (34%): 12 patients had head tremor, 34 patients had arm tremor, whilst 13 patients presented tremor in both sites. Head tremor was postural in all patients, whereas arm tremor was postural/kinetic in 28 patients, only at rest in one and both postural/kinetic and at rest in 18 patients. Patients with tremor were more likely to have segmental/multifocal dystonia. Patients who had rest tremor (either alone or associated with action tremor) had a higher age at dystonia onset and a greater frequency of dystonic arm involvement than patients with action tremor alone or without tremor. Both action and rest tremor are part of the tremor spectrum of adult-onset dystonia and are more frequently encountered in segmental/multifocal dystonia. The higher age at dystonia onset and the greater frequency of arm dystonia in patients with rest tremor may have pathophysiological implications and may account, at least in part, for the previous lack of identification of rest tremor as one possible type of tremor present in dystonia. © 2016 EAN.

Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

PubMed Central

Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

2015-01-01

Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders.

PubMed

Ikonomovic, Milos D; Mi, Zhiping; Abrahamson, Eric E

2017-03-01

Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE). The pathology of TBI is complex and dependent on injury severity, age-at-injury, and length of time between injury and neuropathological evaluation. In addition, the mechanisms influencing pathology and recovery after TBI likely involve genetic/epigenetic factors as well as additional disorders or comorbid states related to age and central and peripheral vascular health. In this regard, dysfunction of the aging neurovascular system could be an important link between TBI and chronic neurodegenerative diseases, either as a precipitating event or related to accumulation of AD-like pathology which is amplified in the context of aging. Thus with advanced age and vascular dysfunction, TBI can trigger self-propagating cycles of neuronal injury, pathological protein aggregation, and synaptic loss resulting in chronic neurodegenerative disease. In this review we discuss evidence supporting TBI and aging as dual, interacting risk factors for AD, and the role of Aβ and cerebral vascular dysfunction in this relationship. Evidence is discussed that Aβ is involved in cyto- and synapto-toxicity after severe TBI, and that its chronic effects are potentiated by aging and impaired cerebral vascular function. From a therapeutic perspective, we emphasize that in the fields of TBI- and aging-related neurodegeneration protective strategies should include preservation of

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by

Juvenile-Onset OCD: Clinical Features in Children, Adolescents and Adults

PubMed Central

Mancebo, Maria C.; Garcia, Abbe M.; Pinto, Anthony; Freeman, Jennifer B.; Przeworski, Amy; Stout, Robert; Kane, Joshua S.; Eisen, Jane L.; Rasmussen, Steven A.

2009-01-01

Objective To examine clinical correlates of juvenile-onset OCD across the lifespan. Method Intake data collected from 257 consecutive participants with a juvenile-onset of OCD (20 children, 44 adolescents, and 193 adults) in a naturalistic study of the clinical course of OCD were examined. Participants and parents of juvenile participants completed a structured diagnostic interview, rater-administered severity measures, and self-report questionnaires. Results Children and adolescents (i.e. juveniles) shared similar features with the exception of age at onset and OCD symptom expression. Clinically meaningful differences between juvenile and adult participants were also found. Compared to adults, juveniles were more likely to be male, recall an earlier age at OCD onset, and have different lifetime comorbidity patterns. Conclusion Juvenile-onset OCD symptom expression is remarkably similar across the lifespan. However, findings also suggest clinically meaningful differences between juveniles and adults. Future work using a prospective design will improve our understanding of course patterns of juvenile-onset OCD. Significant Outcomes •Children were less likely than either adolescent or adults to report aggressive obsessions and mental rituals. •Males were overrepresented in the juvenile sample but gender was equally distributed in the adult sample •Compared to lifetime comorbidity patterns of adults, juveniles showed elevated rates of ADHD and lower rates of mood, substance use and eating disorders Limitations •The cross-sectional design with retrospective recall regarding course prior to study entry limits conclusions about the course of OCD. •The adult sample is limited to adults whose symptoms persisted into adulthood and therefore results cannot be generalized to all individuals with a juvenile-onset. •The small number of very young children (under age 10) may have limited power to detect differences among children and adolescents. PMID:18699949

Delayed-onset progressive movement disorders after static brain lesions.

PubMed

Scott, B L; Jankovic, J

1996-01-01

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Precursors in adolescence of adult-onset bipolar disorder.

PubMed

Hiyoshi, Ayako; Sabet, Julia A; Sjöqvist, Hugo; Melinder, Carren; Brummer, Robert J; Montgomery, Scott

2017-08-15

Although the estimated contribution of genetic factors is high in bipolar disorder, environmental factors may also play a role. This Swedish register-based cohort study of men examined if physical and psychological characteristics in late adolescence, including factors previously linked with bipolar disorder (body mass index, asthma and allergy), are associated with subsequent bipolar disorder in adulthood. Unipolar depression and anxiety are analysed as additional outcomes to identify bipolar disorder-specific associations. A total of 213,693 men born between 1952 and 1956, who participated in compulsory military conscription assessments in late adolescence were followed up to 2009, excluding men with any psychiatric diagnoses at baseline. Cox regression estimated risk of bipolar disorder, depression and anxiety in adulthood associated with body mass index, asthma, allergy, muscular strength stress resilience and cognitive function in adolescence. BMI, asthma and allergy were not associated with bipolar disorder. Higher grip strength, cognitive function and stress resilience were associated with a reduced risk of bipolar disorder and the other disease outcomes. The sample consisted only of men; even though the characteristics in adolescence pre-dated disease onset, they may have been the consequence of prodromal disease. Associations with body mass index and asthma found by previous studies may be consequences of bipolar disorder or its treatment rather than risk factors. Inverse associations with all the outcome diagnoses for stress resilience, muscular strength and cognitive function may reflect general risks for these psychiatric disorders or intermediary factors. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered Bioenergetics in Primary Dermal Fibroblasts from Adult Carriers of the FMR1 Premutation Before the Onset of the Neurodegenerative Disease Fragile X-Associated Tremor/Ataxia Syndrome.

PubMed

Napoli, Eleonora; Song, Gyu; Wong, Sarah; Hagerman, Randi; Giulivi, Cecilia

2016-10-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder, characterized by tremors, ataxia, impaired coordination, and cognitive decline. While all FXTAS individuals are carriers of a 55-200 CGG expansion at the 5'-UTR of the fragile X mental retardation gene (FMR1), also known as premutation, not all carriers develop FXTAS symptoms and some display other types of psychological/emotional disorders (e.g., autism, anxiety). The goal of this study was to investigate whether the mitochondrial dysfunction previously observed in fibroblasts from older premutation individuals (>60 years) was already present in younger (17-48 years), non-FXTAS-affected carriers and to identify the type and severity of the bioenergetic deficit. Since FXTAS affects mostly males, while females account for a small part of the FXTAS-affected population displaying less severe symptoms, only fibroblasts from males were evaluated in this study. Based on polarographic and enzymatic measurements, a generalized OXPHOS deficit was noted accompanied by increases in the matrix biomarker citrate synthase, oxidative stress (as increased mtDNA copy number and deletions), and mitochondrial network disruption/disorganization. Some of the outcomes (ATP-linked oxygen uptake, coupling, citrate synthase activity, and mitochondrial network organization) strongly correlated with the extent of the CGG expansion, with more severe deficits observed in cell lines carrying higher CGG number. Furthermore, mitochondrial outcomes can identify endophenotypes among carriers and are robust predictors of the premutation diagnosis before the onset of FXTAS, with the potential to be used as markers of prognosis and/or as readouts of pharmacological interventions.

The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders.

PubMed

Eira, Jessica; Silva, Catarina Santos; Sousa, Mónica Mendes; Liz, Márcia Almeida

2016-06-01

Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Huntington Disease: A Case Study of Early Onset Presenting as Depression

ERIC Educational Resources Information Center

Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

2004-01-01

Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability.

PubMed

Baker, Emma K; Richdale, Amanda L; Hazi, Agnes; Prendergast, Luke A

2017-07-01

This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression (ASD-Med) and 32 controls participated in the study. Although, the timing of the DLMO did not differ between the two groups, advances and delays of the melatonin rhythm were observed in individual profiles. Overall mean melatonin levels were lower in the ASD-Med group compared to the two other groups. Lastly, greater increases in melatonin in the hour prior to sleep were associated with greater sleep efficiency in the ASD groups.

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data.

PubMed

Vitaliti, Giovanna; Tabatabaie, Omidreza; Matin, Nassim; Ledda, Caterina; Pavone, Piero; Lubrano, Riccardo; Serra, Agostino; Di Mauro, Paola; Cocuzza, Salvatore; Falsaperla, Raffaele

2015-01-01

Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders.

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data

PubMed Central

Vitaliti, Giovanna; Tabatabaie, Omidreza; Matin, Nassim; Ledda, Caterina; Pavone, Piero; Lubrano, Riccardo; Serra, Agostino; Di Mauro, Paola; Cocuzza, Salvatore; Falsaperla, Raffaele

2015-01-01

Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders PMID:26266339

Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

PubMed

Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

2014-11-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

PubMed Central

Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

2014-01-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

Transposable elements in TDP-43-mediated neurodegenerative disorders.

PubMed

Li, Wanhe; Jin, Ying; Prazak, Lisa; Hammell, Molly; Dubnau, Josh

2012-01-01

Elevated expression of specific transposable elements (TEs) has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

Childhood-, teenage-, and adult-onset depression: diagnostic and individual characteristics in a clinical sample.

PubMed

Fernando, Kumari; Carter, Janet D; Frampton, Christopher M A; Luty, Suzanne E; McKenzie, Janice; Mulder, Roger T; Joyce, Peter R

2011-01-01

The age at which a depressive episode is first experienced may be associated with particular individual and clinical characteristics. This study compares individual, clinical, and family characteristics across individuals who experienced their first major depressive episode when a child, teenager, or adult. Participants were 372 depressed outpatients who participated in 2 completed randomized trials for depression. The first compared fluoxetine and nortriptyline, whereas the second compared cognitive behavior therapy and interpersonal psychotherapy. Assessment across the studies included structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I/II diagnoses and a range of self-report measures of symptoms, functioning, and childhood experiences. Participants with childhood- and teenage-onset depression had a greater number of comorbid Axis I diagnoses, were more likely to meet criteria for Avoidant and Paranoid personality disorder (PD), and were more likely to have attempted suicide than those with adult-onset depression. Those with teenage-onset depression were more likely to meet criteria for a PD than those with adult-onset depression. Participants with childhood- and teenage-onset depression reported lower perceptions of paternal care before the age of 16 years, compared to participants with adult-onset depression. Retrospective recall was used to classify individuals into childhood-, teenage-, and adult-onset groups and is subject to recall biases. The sample also consisted of treatment-seeking individuals. There were relatively few differences between teenage and childhood depression. Depressive episodes that begin in childhood or teenage years are associated with more comorbid diagnoses, a higher likelihood of Avoidant and Paranoid PD, a greater likelihood of attempted suicide, and poorer perceptions of paternal care. Compared to adult-onset depression, childhood-onset depression is associated with greater

Etiopathogenesis and Therapeutic Approach to Adult Onset Acne

PubMed Central

Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

2016-01-01

Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14–17 years in females and 16–19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

Pragmatics and adult language disorders: past achievements and future directions.

PubMed

Cummings, Louise

2007-05-01

In this article, the current state of our knowledge of pragmatic disorders in adults with language impairment is assessed. A brief historical background of clinical pragmatics is presented, and the place of adult language pathology within the development of this field is discussed. A comprehensive review is undertaken of pragmatic deficits in adults with language impairments of diverse etiologies. Specifically, pragmatic deficits are examined in adults with left-hemisphere damage, often resulting in aphasia, and in adults with right-hemisphere damage, traumatic brain injury, schizophrenia, and neurodegenerative disorders (principally, Alzheimer's disease). Although many pragmatic phenomena have been examined in these clinical populations, studies have also tended to neglect important areas of pragmatic functioning in adults with these disorders. Several such areas are identified within a wider discussion of how researchers and clinicians can best pursue future investigations of pragmatics in adults with language impairment.

Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

PubMed

Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

2016-01-01

The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

PubMed Central

Perluigi, Marzia; Reed, Tanea; Muharib, Tasneem; Hughes, Christopher P.; Robinson, Renã A.S.; Sultana, Rukhsana

2012-01-01

Abstract Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidative-stress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610–1655. PMID:22115501

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

Parkin Regulation and Neurodegenerative Disorders

PubMed Central

Zhang, Cheng-Wu; Hang, Liting; Yao, Tso-Pang; Lim, Kah-Leong

2016-01-01

Parkin is a unique, multifunctional ubiquitin ligase whose various roles in the cell, particularly in neurons, are widely thought to be protective. The pivotal role that Parkin plays in maintaining neuronal survival is underscored by our current recognition that Parkin dysfunction represents not only a predominant cause of familial parkinsonism but also a formal risk factor for the more common, sporadic form of Parkinson’s disease (PD). Accordingly, keen research on Parkin over the past decade has led to an explosion of knowledge regarding its physiological roles and its relevance to PD. However, our understanding of Parkin is far from being complete. Indeed, surprises emerge from time to time that compel us to constantly update the paradigm of Parkin function. For example, we now know that Parkin’s function is not confined to mere housekeeping protein quality control (QC) roles but also includes mitochondrial homeostasis and stress-related signaling. Furthermore, emerging evidence also suggest a role for Parkin in several other major neurodegenerative diseases including Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS). Yet, it remains truly amazing to note that a single enzyme could serve such multitude of functions and cellular roles. Clearly, its activity has to be tightly regulated. In this review, we shall discuss this and how dysregulated Parkin function may precipitate neuronal demise in various neurodegenerative disorders. PMID:26793099

Predictive genetic testing for adult-onset disorders in minors: a critical analysis of the arguments for and against the 2013 ACMG guidelines.

PubMed

Anderson, J A; Hayeems, R Z; Shuman, C; Szego, M J; Monfared, N; Bowdin, S; Zlotnik Shaul, R; Meyn, M S

2015-04-01

The publication of the ACMG recommendations has reignited the debate over predictive testing for adult-onset disorders in minors. Response has been polarized. With this in mind, we review and critically analyze this debate. First, we identify long-standing inconsistencies between consensus guidelines and clinical practice regarding risk assessment for adult-onset genetic disorders in children using family history and molecular analysis. Second, we discuss the disparate assumptions regarding the nature of whole genome and exome sequencing underlying arguments of both supporters and critics, and the role these assumptions play in the arguments for and against reporting. Third, we suggest that implicit differences regarding the definition of best interests of the child underlie disparate conclusions as to the best interests of children in this context. We conclude by calling for clarity and consensus concerning the central foci of this debate. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk factors for the onset of panic and generalised anxiety disorders in the general adult population: a systematic review of cohort studies.

PubMed

Moreno-Peral, Patricia; Conejo-Cerón, Sonia; Motrico, Emma; Rodríguez-Morejón, Alberto; Fernández, Anna; García-Campayo, Javier; Roca, Miquel; Serrano-Blanco, Antoni; Rubio-Valera, Maria; Bellón, Juan Ángel

2014-10-01

We aimed to assess available evidence on risk factors associated with the onset of panic disorder (PD) and/or generalised anxiety disorder (GAD) in cohort studies in the general adult population. Systematic review using MEDLINE, PsycINFO and Embase. Search terms included panic disorder, generalised anxiety disorder, cohort studies and risk factors. We finally selected 21 studies, involving 163,366 persons with a median follow-up of 5 years. 1) Sociodemographic factors: PD was associated with age, female gender, and few economic resources. GAD was associated with age, non-Hispanics and Blacks, being divorced or widowed, and few economic resources. 2) Psychosocial factors: PD was associated with smoking and alcohol problems. GAD was associated with stressful life events in childhood and adulthood, and personality. 3) Physical and mental health factors: PD was associated with the number of physical diseases suffered and the joint hypermobility syndrome. PD was also associated with a parental history of mental disorders, as well as with other anxiety disorders and other mental health problems in the person affected. GAD was associated with a parental history of mental disorders, as well as with other anxiety disorders and other mental health problems in the person affected, plus already having received psychiatric care. Few studies examined the same risk factors. Sociodemographic, psychosocial and mental-physical health risk factors were determinant for the onset of PD and GAD in the general adult population. These findings could be useful for developing preventive interventions in PD and GAD. Copyright © 2014 Elsevier B.V. All rights reserved.

Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality, functional impairment, and family function.

PubMed

Lin, Yu-Ju; Lo, Kuan-Wu; Yang, Li-Kuang; Gau, Susan Shur-Fen

2015-12-01

The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n=147) and late-onset ADHD (onset between 7 and 12 years, n=42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

PubMed

Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

2017-02-15

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Oligonucleotide therapeutics in neurodegenerative diseases.

PubMed

Scoles, Daniel R; Pulst, Stefan M

2018-03-21

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.

Driving and Neurodegenerative Diseases

PubMed Central

Uc, Ergun Y.; Rizzo, Matthew

2011-01-01

The proportion of elderly in the general population is rising, resulting in greater numbers of drivers with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). These neurodegenerative disorders impair cognition, visual perception, and motor function, leading to reduced driver fitness and greater crash risk. Yet medical diagnosis or age alone is not reliable enough to predict driver safety or crashes, or revoke the driving privileges of these drivers. Driving research utilizes tools such as questionnaires about driving habits and history, driving simulators, standardized road tests utilizing instrumented vehicles, and state driving records. Research challenges include outlining the evolution of driving safety, understanding the mechanisms of driving impairment, and developing a reliable and efficient standardized test battery for prediction of driver safety in neurodegenerative disorders. This information will enable healthcare providers to advise their patients with neurodegenerative disorders with more certainty, affect policy, and help to develop rehabilitative measures for driving. PMID:18713573

Cerebellar pathology in childhood-onset vs. adult-onset essential tremor.

PubMed

Louis, Elan D; Kuo, Sheng-Han; Tate, William J; Kelly, Geoffrey C; Faust, Phyllis L

2017-10-17

Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death. Copyright © 2017 Elsevier B.V. All rights reserved.

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

PubMed

Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

2004-03-01

Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the

Adult Neurogenesis and Neurodegenerative Diseases: A Systems Biology Perspective

PubMed Central

Horgusluoglu, Emrin; Nudelman, Kelly; Nho, Kwangsik; Saykin, Andrew J.

2016-01-01

New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. PMID:26879907

Mitochondrial Hsp60 Chaperonopathy Causes an Autosomal-Recessive Neurodegenerative Disorder Linked to Brain Hypomyelination and Leukodystrophy

PubMed Central

Magen, Daniella; Georgopoulos, Costa; Bross, Peter; Ang, Debbie; Segev, Yardena; Goldsher, Dorit; Nemirovski, Alexandra; Shahar, Eli; Ravid, Sarit; Luder, Anthony; Heno, Bayan; Gershoni-Baruch, Ruth; Skorecki, Karl; Mandel, Hanna

2008-01-01

Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration. PMID:18571143

War and first onset of suicidality: the role of mental disorders

PubMed Central

Karam, E. G.; Salamoun, M. M.; Mneimneh, Z. N.; Fayyad, J. A.; Karam, A. N.; Hajjar, R.; Dimassi, H.; Nock, M. K.; Kessler, R. C.

2014-01-01

Background Suicide rates increase following periods of war; however, the mechanism through which this occurs is not known. The aim of this paper is to shed some light on the associations of war exposure, mental disorders, and subsequent suicidal behavior. Method A national sample of Lebanese adults was administered the Composite International Diagnostic Interview to collect data on lifetime prevalence and age of onset of suicide ideation, plan, and attempt, and mental disorders, in addition to information about exposure to stressors associated with the 1975–1989 Lebanon war. Results The onset of suicide ideation, plan, and attempt was associated with female gender, younger age, post-war period, major depression, impulse-control disorders, and social phobia. The effect of post-war period on each type of suicide outcome was largely explained by the post-war onset of mental disorders. Finally, the conjunction of having a prior impulse-control disorder and either being a civilian in a terror region or witnessing war-related stressors was associated with especially high risk of suicide attempt. Conclusions The association of war with increased risk of suicidality appears to be partially explained by the emergence of mental disorders in the context of war. Exposure to war may exacerbate disinhibition among those who have prior impulse-control disorders, thus magnifying the association of mental disorders with suicidality. PMID:22370047

War and first onset of suicidality: the role of mental disorders.

PubMed

Karam, E G; Salamoun, M M; Mneimneh, Z N; Fayyad, J A; Karam, A N; Hajjar, R; Dimassi, H; Nock, M K; Kessler, R C

2012-10-01

Suicide rates increase following periods of war; however, the mechanism through which this occurs is not known. The aim of this paper is to shed some light on the associations of war exposure, mental disorders, and subsequent suicidal behavior. A national sample of Lebanese adults was administered the Composite International Diagnostic Interview to collect data on lifetime prevalence and age of onset of suicide ideation, plan, and attempt, and mental disorders, in addition to information about exposure to stressors associated with the 1975-1989 Lebanon war. The onset of suicide ideation, plan, and attempt was associated with female gender, younger age, post-war period, major depression, impulse-control disorders, and social phobia. The effect of post-war period on each type of suicide outcome was largely explained by the post-war onset of mental disorders. Finally, the conjunction of having a prior impulse-control disorder and either being a civilian in a terror region or witnessing war-related stressors was associated with especially high risk of suicide attempt. The association of war with increased risk of suicidality appears to be partially explained by the emergence of mental disorders in the context of war. Exposure to war may exacerbate disinhibition among those who have prior impulse-control disorders, thus magnifying the association of mental disorders with suicidality.

Antidepressants and REM Sleep Behavior Disorder: Isolated Side Effect or Neurodegenerative Signal?

PubMed Central

Postuma, Ronald B.; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y.

2013-01-01

Objectives: Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Design: Prospective cohort study. Setting: Tertiary sleep disorders center. Participants: 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Measurements/Results: Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Conclusions: Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with “purely-idiopathic” RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative

Childhood separation anxiety disorder and adult onset panic attacks share a common genetic diathesis.

PubMed

Roberson-Nay, Roxann; Eaves, Lindon J; Hettema, John M; Kendler, Kenneth S; Silberg, Judy L

2012-04-01

Childhood separation anxiety disorder (SAD) is hypothesized to share etiologic roots with panic disorder. The aim of this study was to estimate the genetic and environmental sources of covariance between childhood SAD and adult onset panic attacks (AOPA), with the primary goal to determine whether these two phenotypes share a common genetic diathesis. Participants included parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs) participating in the Virginia Twin Study of Adolescent Behavioral Development and those twins who later completed the Young Adult Follow-Up (YAFU). The Child and Adolescent Psychiatric Assessment was completed at three waves during childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R at the YAFU. Two separate, bivariate Cholesky models were fit to childhood diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation with AOPA; a trivariate Cholesky model also examined the collective influence of childhood SAD and OAD on AOPA. In the best-fitting bivariate model, the covariation between SAD and AOPA was accounted for by genetic and unique environmental factors only, with the genetic factor associated with childhood SAD explaining significant variance in AOPA. Environmental risk factors were not significantly shared between SAD and AOPA. By contrast, the genetic factor associated with childhood OAD did not contribute significantly to AOPA. Results of the trivariate Cholesky reaffirmed outcomes of bivariate models. These data indicate that childhood SAD and AOPA share a common genetic diathesis that is not observed for childhood OAD, strongly supporting the hypothesis of a specific genetic etiologic link between the two phenotypes. © 2012 Wiley Periodicals, Inc.

BAC to degeneration bacterial artificial chromosome (BAC)-mediated transgenesis for modeling basal ganglia neurodegenerative disorders.

PubMed

Lu, Xiao-Hong

2009-01-01

Basal ganglia neurodegenerative disorders, such as Parkinson's disease (PD) and Huntington's disease (HD), are characterized by not only spectrum of motor deficits, ranging form hypokinesia to hyperkinesia, but also emotional, cognitive, and psychiatric manifestations. The symptoms and pathogenic mechanism of these disorders should be viewed as dysfunctions of specific cortico-subcortical neurocircuits. Transgenic approaches using large genomic inserts, such as bacterial artificial chromosome (BAC)-mediated transgenesis, due to its capacity to propagate large-size genomic DNA and faithful production of endogenous-like gene expression pattern/lever, have provided an ideal basis for the generation of transgenic mice as model for basal ganglia neurodegenerative disorders, as well as the functional and structural analysis of neurocircuits. In this chapter, the basic concepts and practical approaches about application of BAC transgenic system are introduced. Existent major BAC transgenic mouse models for PD and HD are evaluated according to their construct, face, and predicative validity. Finally, considerations, possible solutions, and future perspectives of using BAC transgenic approach to study basal ganglia neurodegenerative disorders are discussed.

Endocannabinoid system in neurodegenerative disorders.

PubMed

Basavarajappa, Balapal S; Shivakumar, Madhu; Joshi, Vikram; Subbanna, Shivakumar

2017-09-01

Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs. © 2017 International Society for Neurochemistry.

Iron in neurodegenerative disorders: being in the wrong place at the wrong time?

PubMed

Apostolakis, Sotirios; Kypraiou, Anna-Maria

2017-11-27

Brain iron deposits have been reported consistently in imaging and histologic examinations of patients with neurodegenerative disorders. While the origins of this finding have not been clarified yet, it is speculated that impaired iron homeostasis or deficient transport mechanisms result in the accumulation of this highly toxic metal ultimately leading to formation of reactive oxygen species and cell death. On the other hand, there are also those who support that iron is just an incidental finding, a by product of neuronal loss. A literature review has been performed in order to present the key findings in support of the iron hypothesis of neurodegeneration, as well as to identify conditions causing or resulting from iron overload and compare and contrast their features with the most prominent neurodegenerative disorders. There is an abundance of experimental and observational findings in support of the hypothesis in question; however, as neurodegeneration is a rare incident of commonly encountered iron-associated disorders of the nervous system, and this metal is found in non-neurodegenerative disorders as well, it is possible that iron is the result or even an incidental finding in neurodegeneration. Understanding the underlying processes of iron metabolism in the brain and particularly its release during cell damage is expected to provide a deeper understanding of the origins of neurodegeneration in the years to come.

The emergence of designed multiple ligands for neurodegenerative disorders.

PubMed

Geldenhuys, Werner J; Youdim, Moussa B H; Carroll, Richard T; Van der Schyf, Cornelis J

2011-09-01

The incidence of neurodegenerative diseases has seen a constant increase in the global population, and is likely to be the result of extended life expectancy brought about by better health care. Despite this increase in the incidence of neurodegenerative diseases, there has been a dearth in the introduction of new disease-modifying therapies that are approved to prevent or delay the onset of these diseases, or reverse the degenerative processes in brain. Mounting evidence in the peer-reviewed literature shows that the etiopathology of these diseases is extremely complex and heterogeneous, resulting in significant comorbidity and therefore unlikely to be mitigated by any drug acting on a single pathway or target. A recent trend in drug design and discovery is the rational design or serendipitous discovery of novel drug entities with the ability to address multiple drug targets that form part of the complex pathophysiology of a particular disease state. In this review we discuss the rationale for developing such multifunctional drugs (also called designed multiple ligands or DMLs), and why these drug candidates seem to offer better outcomes in many cases compared to single-targeted drugs in pre-clinical studies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Examples are drawn from the literature of drug candidates that have already reached the market, some unsuccessful attempts, and others that are still in the drug development pipeline. Copyright © 2011. Published by Elsevier Ltd.

Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms--pediatric versus adult?

PubMed

Kumar, Nilay; Bashar, Qumseya; Reddy, Naveen; Sengupta, Jyotirmoy; Ananthakrishnan, Ashwin; Schroeder, Abigail; Hogan, Walter J; Venkatesan, Thangam

2012-05-28

Cyclic Vomiting Syndrome (CVS) is a well-recognized functional gastrointestinal disorder in children but its presentation is poorly understood in adults. Genetic differences in pediatric-onset (presentation before age 18) and adult-onset CVS have been reported recently but their clinical features and possible differences in response to therapy have not been well studied. This was a retrospective review of 101 CVS patients seen at the Medical College of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the diagnosis of CVS. Our study population comprised of 29(29%) pediatric-onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 ± 7 years) in the pediatric-onset group when compared to (5 ± 7 years) adult-onset CVS group (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group compared to adult-onset patients (0% vs. 23%, p = 0.004). Aside from these differences, the two groups were similar with regards to their clinical features and the time of onset of symptoms did not predict response to standard treatment. The majority of patients (86%) responded to treatment with tricyclic antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine. Non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of emergency department visits in the year prior to presentation, presence of disability and non-compliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response. (88% vs. 38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05). Despite reported genetic differences, the clinical features and

Novel Antipsychotics in the Treatment of Behavioral Disturbances and Psychoses Associated With Neurodegenerative Disorders

PubMed Central

Masand, Prakash S.

2000-01-01

Behavioral disturbances and psychosis are common features of neurodegenerative disorders and may be drug induced, intrinsic to the underlying pathology, or both. These disturbances, including psychotic and mood symptoms, apathy, aggression and other behavioral symptoms, and superimposed delirium, cause a great amount of disability to the patient and stress on the caregiver. Conventional neuroleptics have been shown to be effective in the treatment of these symptoms, but unacceptable side effects may occur. However, the novel antipsychotics, with their lower risk of inducing extrapyramidal symptoms, have shown promise in the treatment of behavioral disturbances and psychosis associated with neurodegenerative disorders. PMID:15014653

Age of onset and the subclassification of conduct/dissocial disorder

PubMed Central

Silberg, Judy; Moore, Ashlee A.; Rutter, Michael

2015-01-01

Background Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. Methods The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Results Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Conclusions Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial

Age of onset and the subclassification of conduct/dissocial disorder.

PubMed

Silberg, Judy; Moore, Ashlee A; Rutter, Michael

2015-07-01

Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurrence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. © 2014

Comorbid psychiatric disorders in female adolescents with first-onset anorexia nervosa.

PubMed

Bühren, K; Schwarte, R; Fluck, F; Timmesfeld, N; Krei, M; Egberts, K; Pfeiffer, E; Fleischhaker, C; Wewetzer, C; Herpertz-Dahlmann, B

2014-01-01

Patients with anorexia nervosa (AN) exhibit high rates of psychiatric comorbidity. To disentangle the effects of duration of illness on comorbid psychiatric symptoms, we investigated the rates of comorbid psychiatric disorders, suicidality and self-harm behaviour in adolescent patients with a first onset of AN. In adolescent females (n = 148) with a first onset of AN, body mass index, psychiatric comorbidity (according to DSM-IV), depressive symptoms, suicidality and self-injurious behaviour were assessed. Seventy patients (47.3%) met the criteria for at least one comorbid psychiatric disorder. The binge-purging subtype was associated with increased rates of psychiatric comorbidity, suicidality and self-injurious behaviour. The severity of eating disorder-specific psychopathology influenced current psychiatric comorbidity and suicidal ideation. Prevalence rates of comorbid psychiatric disorders and suicidal ideation are considerably lower among adolescents with AN compared with adults. An early and careful assessment, along with adequate treatment of the eating disorder, might prevent the development of severe psychiatric comorbidities. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives

PubMed Central

Herradón, G; Pérez-García, C

2014-01-01

Midkine (MK) and pleiotrophin (PTN) are two neurotrophic factors that are highly up-regulated in different brain regions after the administration of various drugs of abuse and in degenerative areas of the brain. A deficiency in both MK and PTN has been suggested to be an important genetic factor, which confers vulnerability to the development of the neurodegenerative disorders associated with drugs of abuse in humans. In this review, evidence demonstrating that MK and PTN limit the rewarding effects of drugs of abuse and, potentially, prevent drug relapse is compiled. There is also convincing evidence that MK and PTN have neuroprotective effects against the neurotoxicity and development of neurodegenerative disorders induced by drugs of abuse. Exogenous administration of MK and/or PTN into the CNS by means of non-invasive methods is proposed as a novel therapeutic strategy for addictive and neurodegenerative diseases. Identification of new molecular targets downstream of the MK and PTN signalling pathways or pharmacological modulation of those already known may also provide a more traditional, but probably effective, therapeutic strategy for treating addictive and neurodegenerative disorders. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:23889475

Factors Associated With the Persistence and Onset of New Anxiety Disorders in Youth With Bipolar Spectrum Disorders

PubMed Central

Sala, Regina; Axelson, David A.; Castro-Fornieles, Josefina; Goldstein, Tina R.; Goldstein, Benjamin I.; Ha, Wonho; Liao, Fangzi; Gill, Mary Kay; Iyengar, Satish; Strober, Michael A.; Yen, Shirley; Hower, Heather; Hunt, Jeffrey I.; Dickstein, Daniel P.; Ryan, Neal D.; Keller, Martin B.; Birmaher, Boris

2013-01-01

Objective Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder, but, to our knowledge, no studies examined the course of anxiety disorders in youth and adults with bipolar disorder. Method As part of the Course and Outcome of Bipolar Youth study, 413 youth, ages 7 to 17 years who met criteria for Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) bipolar I disorder (n = 244), bipolar II disorder (n = 28), and operationally defined bipolar disorder not otherwise specified (n = 141) were recruited primarily from outpatient clinics. Subjects were followed on average for 5 years using the Longitudinal Interval Follow-Up Evaluation. We examined factors associated with the persistence (> 50% of the follow-up time) and onset of new anxiety disorders in youth with bipolar disorder. Results Of the 170 youth who had anxiety at intake, 80.6% had an anxiety disorder at any time during the follow-up. Most of the anxiety disorders during the follow-up were of the same type as those present at intake. About 50% of the youth had persistent anxiety, particularly generalized anxiety disorder (GAD). Persistence was associated with multiple anxiety disorders, less follow-up time in euthymia, less conduct disorder, and less treatment with antimanic and antidepressant medications (all P values ≤ .05). Twenty-five percent of the sample who did not have an anxiety disorder at intake developed new anxiety disorders during follow-up, most commonly GAD. The onset of new anxiety disorders was significantly associated with being female, lower socioeconomic status, presence of attention-deficit/hyperactivity disorder and substance use disorder, and more follow-up time with manic or hypomanic symptoms (all P values ≤ .05) Conclusions Anxiety disorders in youth with bipolar disorder tend to persist, and new-onset anxiety disorders developed in a substantial proportion of the sample. Early identification of factors associated with the

Cooler biologically compatible core body temperatures may prolong longevity and combat neurodegenerative disorders.

PubMed

Salerian, Alen J; Saleri, Nansen G

2006-01-01

Scientific evidence suggests the critical role of temperature in regulating three mechanisms contributing to cellular damage: Oxidative stress, oxygen demand overload and inflammation. In this article, we propose that the Arrhenius rate law has a profound impact on aging and a variety of neurodegenerative disorders including Alzheimer's disease, and we review the supporting evidence. Published studies suggest empirical correlations between temperature and lifespan of various organisms, bolstering the hypothesis that variations in lifespan may stem from differences in the mitochondrial production rates of radicals - a process also influenced by temperature. Given the exponential temperature dependency of all biochemical factors, cooler body temperatures may promote longevity and combat neurodegenerative disorders. This promises to offer extraordinary yet unexplored weapons against two formidable enemies of the human body: aging and neurodegenerative disorders. Stated in the form of a thesis referred to as Salerian and Saleri Temperature Thesis (SSTT): "Cooler biologically compatible core body temperatures prolong lifespan and are of value to combat illness". Double blind studies of SSTT in therapeutic strategies against amyotrophic lateral sclerosis (ALS) or early-stage Alzheimer's disease may offer a reasonable first stage to validate SSTT. In view of the known rapid progressive neurodegeneration associated with ALS, minute variations in core body temperature may, in fact, demonstrate statistically significant differences in disease progression.

Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

PubMed

Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

2016-08-01

Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Age at onset versus family history and clinical outcomes in 1,665 international bipolar-I disorder patients

PubMed Central

BALDESSARINI, ROSS J.; TONDO, LEONARDO; VAZQUEZ, GUSTAVO H.; UNDURRAGA, JUAN; BOLZANI, LORENZA; YILDIZ, AYSEGUL; KHALSA, HARI-MANDIR K.; LAI, MASSIMO; LEPRI, BEATRICE; LOLICH, MARIA; MAFFEI, PIER MARIO; SALVATORE, PAOLA; FAEDDA, GIANNI L.; VIETA, EDUARD; MAURICIO, TOHEN

2012-01-01

Early onset in bipolar disorder (BPD) has been associated with greater familial risk and unfavorable clinical outcomes. We pooled data from seven international centers to analyze the relationships of family history and symptomatic as well as functional measures of adult morbidity to onset age, or onset in childhood (age <12), adolescence (12-18), or adulthood (19-55 years). In 1,665 adult, DSM-IV BPD-I patients, onset was 5% in childhood, 28% in adolescence, and 53% at peak ages 15-25. Adolescent and adult onset did not differ by symptomatic morbidity (episodes/year, percentage of months ill, co-morbidity, hospitalization, suicide attempts) or family history. Indications of favorable adult functional outcomes (employment, living independently, marriage and children, and a composite measure including education) ranked, by onset: adult > adolescent > child. Onset in childhood versus adolescence had more episodes/year and more psychiatric co-morbidity. Family history was most prevalent with childhood onset, similar over onset ages 12-40 years, and fell sharply thereafter. Multivariate modeling sustained the impression that family history and poor functional, but not symptomatic, outcomes were associated with younger, especially childhood onset. Early onset was more related to poor functional outcomes than greater symptomatic morbidity, with least favorable outcomes and greater family history with childhood onset. PMID:22295008

Reduced immunity to measles in adults with major depressive disorder.

PubMed

Ford, Bart N; Yolken, Robert H; Dickerson, Faith B; Teague, T Kent; Irwin, Michael R; Paulus, Martin P; Savitz, Jonathan

2018-03-19

Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.

AMPD2 Regulates GTP Synthesis and is Mutated in a Potentially-Treatable Neurodegenerative Brainstem Disorder

PubMed Central

Akizu, Naiara; Cantagrel, Vincent; Schroth, Jana; Cai, Na; Vaux, Keith; McCloskey, Douglas; Naviaux, Robert K.; Vleet, Jeremy Van; Fenstermaker, Ali G.; Silhavy, Jennifer L.; Scheliga, Judith S.; Toyama, Keiko; Morisaki, Hiroko; Sonmez, Fatma Mujgan; Celep, Figen; Oraby, Azza; Zaki, Maha S.; Al-Baradie, Raidah; Faqeih, Eissa; Saleh, Mohammad; Spencer, Emily; Rosti, Rasim Ozgur; Scott, Eric; Nickerson, Elizabeth; Gabriel, Stacey; Morisaki, Takayuki; Holmes, Edward W.; Gleeson, Joseph G.

2013-01-01

Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a new distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new, potentially treatable early-onset neurodegenerative disease. PMID:23911318

Iron biomineralization of brain tissue and neurodegenerative disorders

NASA Astrophysics Data System (ADS)

Mikhaylova (Mikhailova), Albina

The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies

Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

PubMed Central

Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai

2014-01-01

Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.

PubMed

Hagenaars, Saskia P; Radaković, Ratko; Crockford, Christopher; Fawns-Ritchie, Chloe; Harris, Sarah E; Gale, Catharine R; Deary, Ian J

2018-01-01

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.

Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target

PubMed Central

Cassano, Tommaso; Calcagnini, Silvio; Pace, Lorenzo; De Marco, Federico; Romano, Adele; Gaetani, Silvana

2017-01-01

As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis. In particular, the up-regulation of type-2 cannabinoid (CB2) receptors has been found in a number of neurodegenerative disorders. Thus, the modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neuronal degeneration. For these reasons this review will focus on the CB2 receptor as a promising pharmacological target in a number of neurodegenerative diseases. PMID:28210207

Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

PubMed

Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

2016-07-01

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. © The Author(s) 2016.

Lifetime Prevalence of Mental Disorders in Lebanon: First Onset, Treatment, and Exposure to War

PubMed Central

Karam, Elie G; Mneimneh, Zeina N; Dimassi, Hani; Fayyad, John A; Karam, Aimee N; Nasser, Soumana C; Chatterji, Somnath; Kessler, Ronald C

2008-01-01

Background There are no published data on national lifetime prevalence and treatment of mental disorders in the Arab region. Furthermore, the effect of war on first onset of disorders has not been addressed previously on a national level, especially in the Arab region. Thus, the current study aims at investigating the lifetime prevalence, treatment, age of onset of mental disorders, and their relationship to war in Lebanon. Methods and Findings The Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation study was carried out on a nationally representative sample of the Lebanese population (n = 2,857 adults). Respondents were interviewed using the fully structured WHO Composite International Diagnostic Interview 3.0. Lifetime prevalence of any Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder was 25.8%. Anxiety (16.7%) and mood (12.6%) were more common than impulse control (4.4%) and substance (2.2%) disorders. Only a minority of people with any mental disorder ever received professional treatment, with substantial delays (6 to 28 y) between the onset of disorders and onset of treatment. War exposure increased the risk of first onset of anxiety (odds ratio [OR] 5.92, 95% confidence interval [CI] 2.5–14.1), mood (OR 3.32, 95% CI 2.0–5.6), and impulse control disorders (OR 12.72, 95% CI 4.5–35.7). Conclusions About one-fourth of the sample (25.8%) met criteria for at least one of the DSM-IV disorders at some point in their lives. There is a substantial unmet need for early identification and treatment. Exposure to war events increases the odds of first onset of mental disorders. PMID:18384228

Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.

PubMed

Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe

2018-02-12

There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since

Personality disorder traits as predictors of subsequent first-onset panic disorder or agoraphobia

PubMed Central

Bienvenu, O. Joseph; Stein, Murray B.; Samuels, Jack F.; Onyike, Chiadi U.; Eaton, William W.; Nestadt, Gerald

2009-01-01

Determining how personality disorder traits and panic disorder and/or agoraphobia relate longitudinally is an important step in developing a comprehensive understanding of the etiology of panic/agoraphobia. In 1981, a probabilistic sample of adult (≥ 18 years old) residents of east Baltimore were assessed for Axis I symptoms and disorders using the Diagnostic Interview Schedule (DIS); psychiatrists re-evaluated a sub-sample of these participants and made Axis I diagnoses, as well as ratings of individual DSM-III personality disorder traits. Of the participants psychiatrists examined in 1981, 432 were assessed again in 1993–1996 using the DIS. Excluding participants who had baseline panic attacks or panic-like spells from the risk groups, baseline timidity (avoidant, dependent, and related traits) predicted first-onset DIS panic disorder or agoraphobia over the follow-up period. These results suggest that avoidant and dependent personality traits are predisposing factors, or at least markers of risk, for panic disorder and agoraphobia - not simply epiphenomena. PMID:19374963

AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder.

PubMed

Akizu, Naiara; Cantagrel, Vincent; Schroth, Jana; Cai, Na; Vaux, Keith; McCloskey, Douglas; Naviaux, Robert K; Van Vleet, Jeremy; Fenstermaker, Ali G; Silhavy, Jennifer L; Scheliga, Judith S; Toyama, Keiko; Morisaki, Hiroko; Sonmez, Fatma M; Celep, Figen; Oraby, Azza; Zaki, Maha S; Al-Baradie, Raidah; Faqeih, Eissa A; Saleh, Mohammed A M; Spencer, Emily; Rosti, Rasim Ozgur; Scott, Eric; Nickerson, Elizabeth; Gabriel, Stacey; Morisaki, Takayuki; Holmes, Edward W; Gleeson, Joseph G

2013-08-01

Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acid synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH) due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a potentially treatable early-onset neurodegenerative disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Mitochondria: the next (neurode)generation

PubMed Central

Schon, Eric A.; Przedborski, Serge

2012-01-01

SUMMARY Adult-onset neurodegenerative disorders are disabling and often fatal diseases of the nervous system whose underlying mechanisms of cell death remain, in most instances, unknown. Defects in mitochondrial respiration had previously been proposed to contribute to the occurrence of many, if not all of the most common neurodegenerative disorders. However, the discovery of genes mutated in hereditary forms of these enigmatic diseases has additionally suggested defects in mitochondrial dynamics. Such disturbances can lead to changes in mitochondrial trafficking, in interorganellar communication, and in mitochondrial quality control. These new mechanisms by which mitochondria may also be linked to neurodegeneration will likely have far-reaching implications for our understanding of the pathophysiology and treatment of adult-onset neurodegenerative disorders. PMID:21689593

Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

PubMed

Lin, Yu-Ju; Gau, Susan Shur-Fen

2017-09-01

We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

Vergence and Strabismus in Neurodegenerative Disorders

PubMed Central

Kang, Sarah L.; Shaikh, Aasef G.; Ghasia, Fatema F.

2018-01-01

Maintaining proper eye alignment is necessary to generate a cohesive visual image. This involves the coordination of complex neural networks, which can become impaired by various neurodegenerative diseases. When the vergence system is affected, this can result in strabismus and disorienting diplopia. While previous studies have detailed the effect of these disorders on other eye movements, such as saccades, relatively little is known about strabismus. Here, we focus on the prevalence, clinical characteristics, and treatment of strabismus and disorders of vergence in Parkinson’s disease, spinocerebellar ataxia, Huntington disease, and multiple system atrophy. We find that vergence abnormalities may be more common in these disorders than previously thought. In Parkinson’s disease, the evidence suggests that strabismus is related to convergence insufficiency; however, it is responsive to dopamine replacement therapy and can, therefore, fluctuate with medication “on” and “off” periods throughout the day. Diplopia is also established as a side effect of deep brain stimulation and is thought to be related to stimulation of the subthalamic nucleus and extraocular motor nucleus among other structures. In regards to the spinocerebellar ataxias, oculomotor symptoms are common in many subtypes, but diplopia is most common in SCA3 also known as Machado–Joseph disease. Ophthalmoplegia and vergence insufficiency have both been implicated in strabismus in these patients, but cannot fully explain the properties of the strabismus, suggesting the involvement of other structures as well. Strabismus has not been reported as a common finding in Huntington disease or atypical parkinsonian syndromes and more studies are needed to determine how these disorders affect binocular alignment.

Investigation of C9orf72 in 4 Neurodegenerative Disorders

PubMed Central

Xi, Zhengrui; Zinman, Lorne; Grinberg, Yakov; Moreno, Danielle; Sato, Christine; Bilbao, Juan M.; Ghani, Mahdi; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Morón, Francisco J.; Lang, Anthony E.; Marras, Connie; Bruni, Amalia; Colao, Rosanna; Maletta, Raffaele G.; Puccio, Gianfranco; Rainero, Innocenzo; Pinessi, Lorenzo; Galimberti, Daniela; Morrison, Karen E.; Moorby, Catriona; Stockton, Joanne D.; Masellis, Mario; Black, Sandra E.; Hazrati, Lili-Naz; Liang, Yan; van Haersma de With, Jan; Fornazzari, Luis; Villagra, Roque; Rojas-Garcia, Ricardo; Clarimón, Jordi; Mayeux, Richard; Robertson, Janice; St George-Hyslop, Peter; Rogaeva, Ekaterina

2014-01-01

Objective To estimate the allele frequency of C9orf72 (G4C2) repeats in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and Parkinson disease (PD). Design The number of repeats was estimated by a 2-step genotyping strategy. For expansion carriers, we sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2 haplotypes. Setting Hospitals specializing in neurodegenerative disorders. Subjects We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD with the LRRK2 G2019S mutation. Main Outcome Measure The expansion frequency. Results Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3% of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD but not in controls or patients with AD. It was significantly associated with family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS vs FTLD) was not associated with MAPT, APOE, or variability in the repeat flanking regions. Two patients with PD were carriers of 39 and 32 repeats with questionable pathological significance, since the 39-repeat allele does not segregate with PD. No expansion or intermediate alleles (20–29 repeats) were found among the G2019S carriers and AD cases with TAR DNA-binding protein 43–positive inclusions. Surprisingly, the frequency of the 10-repeat allele was marginally increased in all 4 neurodegenerative diseases compared with controls, indicating the presence of an unknown risk variation in the C9orf72 locus. Conclusions The C9orf72 expansion is a common cause of ALS and FTLD, but not of AD or PD. Our study raises concern about a reliable cutoff for the pathological repeat number, which is important in the utility of genetic screening. PMID:22964832

Admixture analysis of age of onset in generalized anxiety disorder.

PubMed

Rhebergen, Didi; Aderka, Idan M; van der Steenstraten, Ira M; van Balkom, Anton J L M; van Oppen, Patricia; Stek, Max L; Comijs, Hannie C; Batelaan, Neeltje M

2017-08-01

Age of onset is a marker of clinically relevant subtypes in various medical and psychiatric disorders. Past research has also reported that age of onset in generalized anxiety disorder (GAD) is clinically significant; but, in research to date, arbitrary cut-off ages have been used. In the present study, admixture analysis was used to determine the best fitting model for age of onset distribution in GAD. Data were derived from 459 adults with a diagnosis of GAD who took part in the Netherlands Study of Depression and Anxiety (NESDA). Associations between age of onset subtypes, identified by admixture analysis, and sociodemographic, clinical, and vulnerability factors were examined using univariate tests and multivariate logistic regression analyses. Two age of onset distributions were identified: an early-onset group (24 years of age and younger) and a late-onset group (greater than 24 years of age). Multivariate analysis revealed that early-onset GAD was associated with female gender (OR 2.1 (95%CI 1.4-3.2)), higher education (OR 1.1 (95%CI 1.0-1.2)), and higher neuroticism (OR 1.4 (95%CI 1.1-1.7)), while late-onset GAD was associated with physical illnesses (OR 1.3 (95%CI 1.1-1.7)). Study limitations include the possibility of recall bias given that age of onset was assessed retrospectively, and an inability to detect a possible very-late-onset GAD subtype. Collectively, the results of the study indicate that GAD is characterized by a bimodal age of onset distribution with an objectively determined early cut-off at 24 years of age. Early-onset GAD is associated with unique factors that may contribute to its aetiology; but, it does not constitute a more severe subtype compared to late-onset GAD. Future research should use 24 years of age as the cut-off for early-onset GAD to when examining the clinical relevance of age of onset for treatment efficacy and illness course. Copyright © 2017 Elsevier Ltd. All rights reserved.

Responses to depressed mood and suicide attempt in young adults with a history of childhood-onset mood disorder.

PubMed

Liu, Xianchen; Gentzler, Amy L; George, Charles J; Kovacs, Maria

2009-05-01

Although individuals' responses to their depressed mood are hypothesized to play an important role in the development and maintenance of depression, how these responses might impact the likelihood of suicidal behavior in mood disorders remains largely unexplored. The goal of the current study was to examine whether maladaptive responses to depressed mood are associated with suicide attempts in adults with a history of childhood-onset mood disorder (COMD). Participants included 223 young adult probands with COMD meeting DSM-III or DSM-IV criteria for major depressive disorder or bipolar disorder and 112 controls without a history of psychiatric disorders. All participants were recruited between 1996 and 2004. Probands were followed for 6 to 99 months (median = 32 months). The Responses Styles Questionnaire was used to assess 2 adaptive (distraction and problem solving) and 2 maladaptive (dangerous activity and rumination) ways of coping with depressed mood. Compared to controls, COMD probands scored significantly higher on maladaptive response styles and lower on adaptive styles. Compared to their COMD peers, probands with a history of suicide attempt were less likely to report using distracting activities to manage their depressed mood. However, COMD probands who engaged in dangerous activities in response to depressed mood were more likely to attempt suicide during the follow-up period (hazard ratio = 1.8, 95% CI = 1.2 to 2.8). One of the pathways to suicide attempt in mood disorders may involve maladaptive responses to depressed mood. The assessment of how depressed individuals manage their dysphoric moods, therefore, should be considered an important aspect of treatment and prevention of suicidal behavior. Copyright 2009 Physicians Postgraduate Press, Inc.

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults

PubMed Central

Wegbreit, Ezra; Weissman, Alexandra B; Cushman, Grace K; Puzia, Megan E; Kim, Kerri L; Leibenluft, Ellen; Dickstein, Daniel P

2015-01-01

Objectives Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report their symptoms started in childhood, suggesting BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition in both children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood-onset type-I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study. Methods Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared facial emotion recognition errors among participants with BD (n = 66; ages 7–26 years) and HC participants (n = 87; ages 7–25 years). Complementary analyses investigated errors for child and adult faces. Results A significant diagnosis-by-age interaction indicated that younger BD participants performed worse than expected relative to HC participants their own age. The deficits occurred for both child and adult faces and were particularly strong for angry child faces, which were most often mistaken as sad. Our results were not influenced by medications, comorbidities/substance use, or mood state/global functioning. Conclusions Younger individuals with BD are worse than their peers at this important social skill. This deficit may be an important developmentally salient treatment target, i.e., for cognitive remediation to improve BD youths’ emotion recognition abilities. PMID:25951752

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

PubMed

Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD. �

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder.

PubMed

Lizardi, Humberto; Klein, Daniel N; Shankman, Stewart A

2004-03-01

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.

Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

PubMed

Postuma, Ronald B; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y

2013-11-01

Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Prospective cohort study. Tertiary sleep disorders center. 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.

Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults

PubMed Central

Chorlian, David B.; Rangaswamy, Madhavi; Manz, Niklas; Wang, Jen-Chyong; Dick, Danielle; Almasy, Laura; Bauer, Lance; Bucholz, Kathleen; Foroud, Tatiana; Hesselbrock, Victor; Kang, Sun J.; Kramer, John; Kuperman, Sam; Nurnberger, John; Rice, John; Schuckit, Marc; Tischfield, Jay; Edenberg, Howard J.; Goate, Alison; Bierut, Laura; Porjesz, Bernice

2013-01-01

Discrete time survival analysis (DTSA) was used to assess the age-specific association of event related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2938 adolescents and young adults ages 12 to 25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens. PMID:23963516

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

PubMed

Novarino, Gaia; Fenstermaker, Ali G; Zaki, Maha S; Hofree, Matan; Silhavy, Jennifer L; Heiberg, Andrew D; Abdellateef, Mostafa; Rosti, Basak; Scott, Eric; Mansour, Lobna; Masri, Amira; Kayserili, Hulya; Al-Aama, Jumana Y; Abdel-Salam, Ghada M H; Karminejad, Ariana; Kara, Majdi; Kara, Bulent; Bozorgmehri, Bita; Ben-Omran, Tawfeg; Mojahedi, Faezeh; El Din Mahmoud, Iman Gamal; Bouslam, Naima; Bouhouche, Ahmed; Benomar, Ali; Hanein, Sylvain; Raymond, Laure; Forlani, Sylvie; Mascaro, Massimo; Selim, Laila; Shehata, Nabil; Al-Allawi, Nasir; Bindu, P S; Azam, Matloob; Gunel, Murat; Caglayan, Ahmet; Bilguvar, Kaya; Tolun, Aslihan; Issa, Mahmoud Y; Schroth, Jana; Spencer, Emily G; Rosti, Rasim O; Akizu, Naiara; Vaux, Keith K; Johansen, Anide; Koh, Alice A; Megahed, Hisham; Durr, Alexandra; Brice, Alexis; Stevanin, Giovanni; Gabriel, Stacy B; Ideker, Trey; Gleeson, Joseph G

2014-01-31

Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.

Therapeutic Role and Drug Delivery Potential of Neuroinflammation as a Target in Neurodegenerative Disorders.

PubMed

Singh, Abhijeet; Chokriwal, Ankit; Sharma, Madan Mohan; Jain, Devendra; Saxena, Juhi; Stephen, Bjorn John

2017-08-16

Neuroinflammation, the condition associated with the hyperactivity of immune cells within the CNS (central nervous system), has recently been linked to a host range of neurodegenerative disorders. Targeting neuroinflammation could be of prime importance as recent research highlights the beneficial aspects associated with modulating the inflammatory mediators associated with the CNS. One of the main obstructions in neuroinflammatory treatments is the hindrance posed by the blood-brain barrier for the delivery of drugs. Hence, research has focused on novel modes of transport for drugs to cross the barrier through drug delivery and nanotechnology approaches. In this Review, we highlight the therapeutic advancement made in the field of neurodegenerative disorders by focusing on the effect neuroinflammation treatment has on these conditions.

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease.

PubMed

Megna, Matteo; Patruno, Cataldo; Balato, Anna; Rongioletti, Franco; Stingeni, Luca; Balato, Nicola

2017-08-01

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p < 0.05), itch intensity (higher in adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behaviour.

PubMed

Howard, Richard; Finn, Peter; Jose, Paul; Gallagher, Jennifer

2011-12-16

This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: APA), as follows: neither childhood conduct disorder (CCD) nor alcohol abuse/dependence; CCD but no alcohol abuse or dependence; alcohol abuse/dependence but no CCD; both CCD and alcohol abuse/dependence. The outcome measure was the sum of positive responses to 55 interview items capturing a variety of antisocial behaviours engaged in since age 15. Severity of lifetime alcohol-related and CCD problems served as predictor variables in regression analysis. Antisocial behaviour problems were greatest in individuals with a history of co-occurring conduct disorder (CD) and alcohol abuse/dependence. While CCD was strongly predictive of adult antisocial behaviour, this effect was both mediated and moderated (exacerbated) by AOAA.

Dysthymic disorder in the elderly population.

PubMed

Devanand, D P

2014-01-01

The diagnosis of dysthymic disorder was created in DSM-III and maintained in DSM-IV to describe a depressive syndrome of mild to moderate severity of at least two years' duration that did not meet criteria for major depressive disorder. The prevalence of dysthymic disorder is approximately 2% in the elderly population where subsyndromal depressions of lesser severity are more common. Dysthymic disorder was replaced in DSM-V by the diagnosis of "persistent depressive disorder" that includes chronic major depression and dysthymic disorder. In older adults, epidemiological and clinical evidence supports the use of the term "dysthymic disorder." In contrast to young adults with dysthymic disorder, older adults with dysthymic disorder commonly present with late age of onset, without major depression and other psychiatric disorders, and with a low rate of family history of mood disorders. They often have stressors such as loss of social support and bereavement, and some have cerebrovascular or neurodegenerative pathology. A minority has chronic depression dating from youth with psychiatric comorbidity similar to young adults with dysthymic disorder. In older adults, both dysthymic disorder and subsyndromal depression increase disability and lead to poor medical outcomes. Elderly patients with dysthymic disorder are seen mainly in primary care where identification and treatment are often inadequate. Treatment with antidepressant medication shows marginal superiority over placebo in controlled trials, and problem-solving therapy shows similar efficacy. Combined treatment and collaborative care models show slightly better results, but cost effectiveness is a concern. Further work is needed to clarify optimal approaches to the treatment of dysthymic disorder in elderly patients.

Sigma-1 receptor chaperones in neurodegenerative and psychiatric disorders

PubMed Central

Pokrass, Michael J; Klauer, Neal R; De Credico, Nicole E

2017-01-01

Introduction Sigma-1 receptors (Sig-1Rs) are molecular chaperones that reside mainly in the endoplasmic reticulum (ER) but exist also in the proximity of the plasma membrane. Sig-1Rs are highly expressed in the CNS and are involved in many cellular processes including cell differentiation, neuritogenesis, microglia activation, protein quality control, calcium-mediated ER stress and ion channel modulation. Disturbance in any of the above cellular processes can accelerate the progression of many neurological disorders; therefore, the Sig-1R has been implicated in several neurological diseases. Areas covered This review broadly covers the functions of Sig-1Rs including several neurodegenerative disorders in humans and drug addiction-associated neurological disturbance in the case of HIV infection. We discuss how several Sig-1R ligands could be utilized in therapeutic approaches to treat those disorders. Expert opinion Emerging understanding of the cellular functions of this unique transmembrane chaperone may lead to the use of new agents or broaden the use of certain available ligands as therapeutic targets in those neurological disorders. PMID:25331742

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults.

PubMed

Wegbreit, Ezra; Weissman, Alexandra B; Cushman, Grace K; Puzia, Megan E; Kim, Kerri L; Leibenluft, Ellen; Dickstein, Daniel P

2015-08-01

Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report that their symptoms started in childhood, suggesting that BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition both in children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood-onset type-I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study. Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared facial emotion recognition errors among participants with BD (n = 66; ages 7-26 years) and HC participants (n = 87; ages 7-25 years). Complementary analyses investigated errors for child and adult faces. A significant diagnosis-by-age interaction indicated that younger BD participants performed worse than expected relative to HC participants their own age. The deficits occurred both for child and adult faces and were particularly strong for angry child faces, which were most often mistaken as sad. Our results were not influenced by medications, comorbidities/substance use, or mood state/global functioning. Younger individuals with BD are worse than their peers at this important social skill. This deficit may be an important developmentally salient treatment target - that is, for cognitive remediation to improve BD youths' emotion recognition abilities. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Targeting innate immunity for neurodegenerative disorders of the central nervous system.

PubMed

Andreasson, Katrin I; Bachstetter, Adam D; Colonna, Marco; Ginhoux, Florent; Holmes, Clive; Lamb, Bruce; Landreth, Gary; Lee, Daniel C; Low, Donovan; Lynch, Marina A; Monsonego, Alon; O'Banion, M Kerry; Pekny, Milos; Puschmann, Till; Russek-Blum, Niva; Sandusky, Leslie A; Selenica, Maj-Linda B; Takata, Kazuyuki; Teeling, Jessica; Town, Terrence; Van Eldik, Linda J

2016-09-01

Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of

Neural abnormalities in early-onset and adolescence-onset conduct disorder.

PubMed

Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

2010-07-01

Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for

Head Trauma as a Precipitating Factor for Late-onset Leigh Syndrome: a Case Report.

PubMed

Ashrafi, Farzad; Pakdaman, Hossein; Arabahmadi, Mehran; Behnam, Behdad

2017-01-01

Leigh syndrome is a severe progressive neurodegenerative disorder with different clinical presentationsthat usually becomes apparent in the first year of life and rarely in late childhood and elderly years. It is causedby failure of mitochondrial respiratory chain and often results in regression of both mental and motor skills and might even lead to death. In some of the inherited neurodegenerative diseases like Alexander disease, head trauma is reported as a trigger for onset of the disease. We present a late onset Leigh syndrome in a 14-year-old girl whose symptoms were initiating following head trauma.

Childhood adversities and first onset of psychiatric disorders in a national sample of adolescents

PubMed Central

McLaughlin, Katie A.; Green, Jennifer Greif; Gruber, Michael J.; Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C.

2012-01-01

Context Although childhood adversities (CAs) are known to be highly co-occurring, most research examines their associations with mental disorders one at a time. Recent evidence from adult studies suggests, though, that the associations of multiple CAs with mental disorders are non-additive, arguing for the importance of multivariate analysis of multiple CAs. No attempt has yet been made to carry out a similar kind of analysis among children or adolescents. Objective To examine the multivariate associations of 12 CAs with first onset of mental disorders in a national sample of US adolescents. Design US national survey of adolescents (ages 13–17) assessing DSM-IV anxiety, mood, behavior, and substance disorders and CAs. The CAs include parental loss (death, divorce, other separations), maltreatment (physical, sexual, and emotional abuse, neglect), parental maladjustment (psychopathology, substance abuse, criminality, violence) and economic adversity. Setting Dual-frame household-school samples. Participants 6,483 adolescents-parent pairs. Main outcome measure Lifetime DSM-IV disorders assessed with the WHO Composite International Diagnostic Interview. Results 58.3% of adolescents reported at least one CA, among whom 59.7% reported multiple CAs. CAs reflecting maladaptive family functioning (MFF) were more strongly associated than other CAs with disorder onsets. The best-fitting model included terms for type and number of CAs and distinguished between MFF and Other CAs. CAs predicted behavior disorders most strongly and fear disorders least strongly. The joint associations of multiple CAs were sub-additive. The population-attributable risk proportions for disorder classes ranged from 15.7% for fear disorders to 40.7% for behavior disorders. CAs were associated with 28.2% of all onsets. Conclusions CAs are common, highly co-occurring, and strongly associated with onset of mental disorders among US adolescents. The sub-additive multivariate associations of CAs with

Is Adolescent-Onset First-Episode Psychosis Different from Adult Onset?

ERIC Educational Resources Information Center

Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-01-01

Objective: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Method: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated…

Lipid peroxidation and neurodegenerative disease.

PubMed

Reed, Tanea T

2011-10-01

Lipid peroxidation is a complex process involving the interaction of oxygen-derived free radicals with polyunsaturated fatty acids, resulting in a variety of highly reactive electrophilic aldehydes. Since 1975, lipid peroxidation has been extensively studied in a variety of organisms. As neurodegenerative diseases became better understood, research establishing a link between this form of oxidative damage, neurodegeneration, and disease has provided a wealth of knowledge to the scientific community. With the advent of proteomics in 1995, the identification of biomarkers for neurodegenerative disorders became of paramount importance to better understand disease pathogenesis and develop potential therapeutic strategies. This review focuses on the relationship between lipid peroxidation and neurodegenerative diseases. It also demonstrates how findings in current research support the common themes of altered energy metabolism and mitochondrial dysfunction in neurodegenerative disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Quantitative analysis on electrooculography (EOG) for neurodegenerative disease

NASA Astrophysics Data System (ADS)

Liu, Chang-Chia; Chaovalitwongse, W. Art; Pardalos, Panos M.; Seref, Onur; Xanthopoulos, Petros; Sackellares, J. C.; Skidmore, Frank M.

2007-11-01

Many studies have documented abnormal horizontal and vertical eye movements in human neurodegenerative disease as well as during altered states of consciousness (including drowsiness and intoxication) in healthy adults. Eye movement measurement may play an important role measuring the progress of neurodegenerative diseases and state of alertness in healthy individuals. There are several techniques for measuring eye movement, Infrared detection technique (IR). Video-oculography (VOG), Scleral eye coil and EOG. Among those available recording techniques, EOG is a major source for monitoring the abnormal eye movement. In this real-time quantitative analysis study, the methods which can capture the characteristic of the eye movement were proposed to accurately categorize the state of neurodegenerative subjects. The EOG recordings were taken while 5 tested subjects were watching a short (>120 s) animation clip. In response to the animated clip the participants executed a number of eye movements, including vertical smooth pursued (SVP), horizontal smooth pursued (HVP) and random saccades (RS). Detection of abnormalities in ocular movement may improve our diagnosis and understanding a neurodegenerative disease and altered states of consciousness. A standard real-time quantitative analysis will improve detection and provide a better understanding of pathology in these disorders.

Nuclear Receptors in Neurodegenerative Diseases

PubMed Central

Skerrett, Rebecca; Malm, Tarja; Landreth, Gary

2014-01-01

Nuclear receptors have generated substantial interest in the past decade as potential therapeutic targets for the treatment of neurodegenerative disorders. Despite years of effort, effective treatments for progressive neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and ALS remain elusive, making non-classical drug targets such as nuclear receptors an attractive alternative. A substantial literature in mouse models of disease and several clinical trials have investigated the role of nuclear receptors in various neurodegenerative disorders, most prominently AD. These studies have met with mixed results, yet the majority of studies in mouse models report positive outcomes. The mechanisms by which nuclear receptor agonists affect disease pathology remain unclear. Deciphering the complex signaling underlying nuclear receptor action in neurodegenerative diseases is essential for understanding this variability in preclinical studies, and for the successful translation of nuclear receptor agonists into clinical therapies. PMID:24874548

Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behaviour

PubMed Central

Howard, Richard; Finn, Peter; Jose, Paul; Gallagher, Jennifer

2012-01-01

This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: APA), as follows: neither childhood conduct disorder (CCD) nor alcohol abuse/dependence; CCD but no alcohol abuse or dependence; alcohol abuse/dependence but no CCD; both CCD and alcohol abuse/dependence. The outcome measure was the sum of positive responses to 55 interview items capturing a variety of antisocial behaviours engaged in since age 15. Severity of lifetime alcohol-related and CCD problems served as predictor variables in regression analysis. Antisocial behaviour problems were greatest in individuals with a history of co-occurring conduct disorder (CD) and alcohol abuse/dependence. While CCD was strongly predictive of adult antisocial behaviour, this effect was both mediated and moderated (exacerbated) by AOAA. PMID:23459369

Autistic-like traits in adult patients with mood disorders and schizophrenia.

PubMed

Matsuo, Junko; Kamio, Yoko; Takahashi, Hidetoshi; Ota, Miho; Teraishi, Toshiya; Hori, Hiroaki; Nagashima, Anna; Takei, Reiko; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

2015-01-01

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of

Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia

PubMed Central

Matsuo, Junko; Kamio, Yoko; Takahashi, Hidetoshi; Ota, Miho; Teraishi, Toshiya; Hori, Hiroaki; Nagashima, Anna; Takei, Reiko; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

2015-01-01

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of

Comorbidity, age of onset and suicidality in obsessive-compulsive disorder (OCD): An international collaboration.

PubMed

Brakoulias, V; Starcevic, V; Belloch, A; Brown, C; Ferrao, Y A; Fontenelle, L F; Lochner, C; Marazziti, D; Matsunaga, H; Miguel, E C; Reddy, Y C J; do Rosario, M C; Shavitt, R G; Shyam Sundar, A; Stein, D J; Torres, A R; Viswasam, K

2017-07-01

To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. Data from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4%; n=1055), obsessive-compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these

Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review.

PubMed

Keightley, Michelle L; Sinopoli, Katia J; Davis, Karen D; Mikulis, David J; Wennberg, Richard; Tartaglia, Maria C; Chen, Jen-Kai; Tator, Charles H

2014-01-01

While generalized cerebral atrophy and neurodegenerative change following traumatic brain injury (TBI) is well recognized in adults, it remains comparatively understudied in the pediatric population, suggesting that research should address the potential for neurodegenerative change in children and youth following TBI. This focused review examines original research findings documenting evidence for neurodegenerative change following TBI of all severities in children and youth. Our relevant inclusion and exclusion criteria identified a total of 16 articles for review. Taken together, the studies reviewed suggest there is evidence for long-term neurodegenerative change following TBI in children and youth. In particular both cross-sectional and longitudinal studies revealed volume loss in selected brain regions including the hippocampus, amygdala, globus pallidus, thalamus, periventricular white matter, cerebellum, and brain stem as well as overall decreased whole brain volume and increased CSF and ventricular space. Diffusion Tensor Imaging (DTI) studies also report evidence for decreased cellular integrity, particularly in the corpus callosum. Sensitivity of the hippocampus and deep limbic structures in pediatric populations are similar to findings in the adult literature and we consider the data supporting these changes as well as the need to investigate the possibility of neurodegenerative onset in childhood associated with mild traumatic brain injury (mTBI).

[Sense of smell, physiological ageing and neurodegenerative diseases: II. Ageing and neurodegenerative diseases].

PubMed

Fusari, A; Molina, J A

The sense of smell, which was once studied because of its biological and evolutionary significance, is today one of the centres of interest in research on normal and pathological ageing. The latest scientific developments point to an inversely proportional relationship between age and olfactory sensitivity. In certain neurodegenerative diseases this sensory decline is one of the first symptoms of the disorder and is correlated with the progression of the disease. In this work we are going to review the scientific knowledge on loss of sense of smell in ageing and in neurodegenerative diseases, with special attention given to Alzheimer's and Parkinson's diseases. A survey of studies that have examined the olfactory deficits in ageing and in some neurodegenerative diseases offers conclusive results about the presence of these impairments in the early stages of these disorders and even among healthy elderly persons. Although a number of causes contribute to these sensory losses in physiological ageing, a common neurological foundation has been proposed for Alzheimer's and Parkinson's diseases. Nevertheless, despite certain initial similarities, the olfactory deficits shown in these disorders seem to be qualitatively different.

The Age of Onset of Anxiety Disorders

PubMed Central

de Lijster, Jasmijn M.; Dierckx, Bram; Utens, Elisabeth M.W.J.; Verhulst, Frank C.; Zieldorff, Carola; Dieleman, Gwen C.

2016-01-01

Objective: The objective was to estimate the age of onset (AOO) for all anxiety disorders and for specific subtypes. Gender differences in the AOO of anxiety disorders were examined, as were the influence of study characteristics on reported AOOs. Methods: Seven electronic databases were searched up to October 2014, with keywords representing anxiety disorder subtypes, AOO, and study design. The inclusion criteria were studies using a general population sample that provided data on the AOO for all anxiety disorders, or specific anxiety disorders, according to DSM-III-R, DSM-IV, or ICD-10 criteria. Results: There were 1028 titles examined, which yielded 24 studies meeting the inclusion criteria. Eight studies reported the AOO and gender. Meta-analysis found a mean AOO of all anxiety disorders of 21.3 years (95% CI 17.46 to 25.07). Separation anxiety disorder, specific phobia, and social phobia had their mean onset before the age of 15 years, whereas the AOO of agoraphobia, obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, and generalized anxiety disorder began, on average, between 21.1 and 34.9 years. Meta-analysis revealed no difference in the AOO between genders. A prospective study design and higher developmental level of the study country were associated with an earlier AOO. Conclusions: Results from this meta-analysis indicate that anxiety disorder subtypes differ in the mean AOO, with onsets ranging from early adolescence to young adulthood. These findings suggest that prevention strategies of anxiety disorders should be directed towards factors associated with the development of anxiety disorder subtypes in the age groups with the greatest vulnerability for developing those disorders. PMID:27310233

ROCK in CNS: Different Roles of Isoforms and Therapeutic Target for Neurodegenerative Disorders.

PubMed

Chong, Cheong-Meng; Ai, Nana; Lee, Simon Ming-Yuen

2017-01-01

Rho-associated protein kinase (ROCK) is a serine-threonine kinase originally identified as a crucial regulator of actin cytoskeleton. Recent studies have defined new functions of ROCK as a critical component of diverse signaling pathways in neurons. In addition, inhibition of ROCK causes several biological events such as increase of neurite outgrowth, axonal regeneration, and activation of prosurvival Akt. Thus, it has attracted scientist's strong attentions and considered ROCK as a promising therapeutic target for the treatment of neurodegenerative disorders including Alzheimer disease, Parkinson's disease, Huntington';s disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, ROCK has two highly homologous isoforms, ROCK1 and ROCK2. Accumulated evidences indicate that ROCK1 and ROCK2 might involve in distinct cellular functions in central nervous system (CNS) and neurodegenerative processes. This review summarizes recent updates regarding ROCK isoformspecific functions in CNS and the progress of ROCK inhibitors in preclinical studies for neurodegenerative diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Adult attention deficit/hyperactivity disorder, associated symptoms and comorbid psychiatric disorders: diagnosis and pharmacological treatment].

PubMed

Paslakis, G; Schredl, M; Alm, B; Sobanski, E

2013-08-01

Adult attention deficit/hyperactivity disorder (ADHD) is characterised by inattention and/or hyperactivity and impulsivity and is a frequent psychiatric disorder with childhood onset. In addition to core symptoms, patients often experience associated symptoms like emotional dysregulation or low self-esteem and suffer from comorbid disorders, particularly depressive episodes, substance abuse, anxiety or sleep disorders. It is recommended to include associated symptoms and comorbid psychiatric disorders in the diagnostic set-up and in the treatment plan. Comorbid psychiatric disorders should be addressed with disorder-specific therapies while associated symptoms also often improve with treatment of the ADHD core symptoms. The most impairing psychiatric disorder should be treated first. This review presents recommendations for differential diagnosis and treatment of adult ADHD with associated symptoms and comorbid psychiatric disorders with respect to internationally published guidelines, clinical trials and expert opinions. © Georg Thieme Verlag KG Stuttgart · New York.

Infantile onset progressive cerebellar atrophy and anterior horn cell degeneration--a late onset variant of PCH-1?

PubMed

Lev, Dorit; Michelson-Kerman, Marina; Vinkler, Chana; Blumkin, Lubov; Shalev, Stavit A; Lerman-Sagie, Tally

2008-03-01

Despite major recent advances in our understanding of developmental cerebellar disorders, classification and delineation of these disorders remains difficult. The term pontocerebellar hypoplasia is used when there is a structural defect, originating in utero of both pons and cerebellar hemispheres. The term olivopontocerebellar atrophy is used when the disorder starts later in life and the process is a primary degeneration of cerebellar neurons. Pontocerebellar hypoplasia type 1 is associated with spinal anterior horn cell degeneration, congenital contractures, microcephaly, polyhydramnion and respiratory insufficiency leading to early death. However, anterior horn cell degeneration has also been described in cases with later onset pontocerebellar atrophy and recently the spectrum has even been further extended to include the association of anterior horn cell degeneration and cerebellar atrophy without pontine involvement. We describe two siblings from a consanguineous Moslem Arabic family who presented with progressive degeneration of both the cerebellum and the anterior horn cells. The patients presented after 1 year of age with a slow neurodegenerative course that included both cognitive and motor functions. There is considerable phenotypic variability; the sister shows a much milder course. Both children are still alive at 6 and 9 years. The sister could still crawl and speak two word sentences at the age of 3 years while the brother was bedridden and only uttered guttural sounds at the same age. Our cases further extend the phenotype of the cerebellar syndromes with anterior horn cell involvement to include a childhood onset and protracted course and further prove that this neurodegenerative disorder may start in utero or later in life.

Determinants of Social Outcomes in Adults With Childhood-onset Epilepsy

PubMed Central

Baca, Christine B.; Rychlik, Karen; Vickrey, Barbara G.; Caplan, Rochelle; Testa, Francine M.; Levy, Susan R.

2016-01-01

BACKGROUND: Adults with childhood-onset epilepsy experience poorer adult social outcomes than their peers. The relative roles of seizures over time versus learning and psychiatric problems are unclear. METHODS: We examined independent influences of psychiatric and learning disorders and of seizure course in 241 young adults (22–35 years old) with uncomplicated epilepsy in a longitudinal community-based cohort study. Social outcomes were ascertained throughout the study. A history of psychiatric and learning problems was ascertained ∼9 years after study entry. Seizure course was: “Excellent,” no seizures after the first year, in complete remission at last contact (N = 95, 39%); “Good,” seizures occurred 1 to 5 years after diagnosis, in complete remission at last contact (N = 56, 23%); “Fluctuating,” more complicated trajectories, but never pharmacoresistant (N = 70, 29%); “Pharmacoresistant,” long-term pharmacoresistant (N = 20, 8%). Multiple logistic regression was used to identify contributors to each social outcome. RESULTS: Better seizure course predicted college completion, being either employed or pursuing a degree, and driving, but was not substantially associated with other social outcomes. Poorer seizure course was associated with a greater likelihood of having offspring, particularly in women without partners. Learning problems, psychiatric disorders, or both negatively influenced all but 2 of the social outcomes. CONCLUSIONS: In young adults with uncomplicated epilepsy, the course of seizures contributed primarily to education, employment, and driving. A history of learning problems and psychiatric disorders adversely influenced most adult outcomes. These findings identify potential reasons for vocational and social difficulties encountered by young adults with childhood epilepsy and areas to target for counseling and transition planning. PMID:26983470

Juvenile and adult-onset psychogenic non-epileptic seizures.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad

2013-09-01

Psychogenic non-epileptic seizures (PNES) tend to begin in adolescence and young adulthood, although the seizures can occur in a wide range of ages. In the current study, we investigated the age of onset in patients with PNES and tried to determine the correlation between the age of onset and the demographic and clinical characteristics and factors potentially predisposing to PNES. In this cross-sectional study, all patients with a clinical diagnosis of PNES were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 to 2012. We dichotomized the patients into two groups; those with age of onset below 18 years (juvenile), and those with age of onset at 18-55 years (adult-onset). We studied the demographic and clinical characteristics and factors potentially predisposing to PNES between these two groups. Statistical analyses were performed using Chi square and Fisher's Exact tests and Mann-Whitney U test. Fifty-seven patients with juvenile and 129 people with adult-onset PNES were studied. Demographic characteristics of these two groups were not different significantly. Seizure characteristics and semiology in these two groups were not significantly different either. However, factors potentially predisposing to PNES were significantly different between these two groups. History of being abused, academic failure, epilepsy or family history of epilepsy were more frequently observed in juvenile PNES, while medical comorbidities were more frequent among patients with adult-onset PNES. Age of onset of PNES is not correlated with the clinical manifestations; however, factors potentially predisposing to PNES are significantly different in patients with juvenile compared to those with adult-onset PNES. Copyright © 2013 Elsevier B.V. All rights reserved.

Autophagy and Human Neurodegenerative Diseases-A Fly's Perspective.

PubMed

Kim, Myungjin; Ho, Allison; Lee, Jun Hee

2017-07-23

Neurodegenerative diseases in humans are frequently associated with prominent accumulation of toxic protein inclusions and defective organelles. Autophagy is a process of bulk lysosomal degradation that eliminates these harmful substances and maintains the subcellular environmental quality. In support of autophagy's importance in neuronal homeostasis, several genetic mutations that interfere with autophagic processes were found to be associated with familial neurodegenerative disorders. In addition, genetic mutations in autophagy-regulating genes provoked neurodegenerative phenotypes in animal models. The Drosophila model significantly contributed to these recent developments, which led to the theory that autophagy dysregulation is one of the major underlying causes of human neurodegenerative disorders. In the current review, we discuss how studies using Drosophila enhanced our understanding of the relationship between autophagy and neurodegenerative processes.

Effects of comorbidity and early age of onset in young people with Bipolar Disorder on self harming behaviour and suicide attempts.

PubMed

Moor, Stephanie; Crowe, Marie; Luty, Sue; Carter, Janet; Joyce, Peter R

2012-02-01

The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (<13 years) patients bearing the greatest burden of disease. Greater comorbidity also significantly increased the risk of having self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. Copyright © 2011 Elsevier B.V. All rights reserved.

[Awareness of adult attention-deficit/hyperactivity disorder (ADHD) in Greece].

PubMed

Pehlivanidis, A

2012-06-01

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopment disorder of childhood that persists into adulthood in the majority of cases. In adults, the clinical picture of ADHD is complex and comorbidity with other psychiatric disorders is the rule. The documentation that the disorder had a childhood onset and the various comorbid symptomatologies present both in childhood and adult life represent the most influential obstacles for the accurate clinical diagnosis of the disorder. In 75% of cases with adult ADHD there is at least one coexisting comorbid disorder, with anxiety and mood disorders as well as substance abuse and impulse control disorders being the most prevalent ones. Adult psychiatrists have limited experience in the diagnosis, treatment and overall management of the disorder. Greece is a member of the European Network Adult ADHD (ENAA), founded in 2003, aiming to increase awareness of the disorder and to improve knowledge and patient care for adults with ADHD across Europe. A clinic where diagnosis as well as treatment recommendations are given after a thorough assessment of adult ADHD patients, is hosted at the First Department of Psychiatry of the Athens National and Kapodistian University. The clinic is in close collaboration with ENAA. The diagnosis of ADHD is given after a detailed evaluation of the patient, based on history taken, self-administered questionnaires and a specific psychiatric interview. The reliable trace of the symptoms' onset back in early childhood, current symptomatology, as well as its impact on at least two major areas of functioning (school, home, work or personal relationships) are pivotal for the assessment procedure. Special attention should be paid in the distinction of symptoms often coexisting with the core symptoms of the ADHD, such as emotional liability, incessant mental activity, avoidance of situations like queuing, especially when there is also frustration, from those indicating a comorbid

Gaussian processes with optimal kernel construction for neuro-degenerative clinical onset prediction

NASA Astrophysics Data System (ADS)

Canas, Liane S.; Yvernault, Benjamin; Cash, David M.; Molteni, Erika; Veale, Tom; Benzinger, Tammie; Ourselin, Sébastien; Mead, Simon; Modat, Marc

2018-02-01

Gaussian Processes (GP) are a powerful tool to capture the complex time-variations of a dataset. In the context of medical imaging analysis, they allow a robust modelling even in case of highly uncertain or incomplete datasets. Predictions from GP are dependent of the covariance kernel function selected to explain the data variance. To overcome this limitation, we propose a framework to identify the optimal covariance kernel function to model the data.The optimal kernel is defined as a composition of base kernel functions used to identify correlation patterns between data points. Our approach includes a modified version of the Compositional Kernel Learning (CKL) algorithm, in which we score the kernel families using a new energy function that depends both the Bayesian Information Criterion (BIC) and the explained variance score. We applied the proposed framework to model the progression of neurodegenerative diseases over time, in particular the progression of autosomal dominantly-inherited Alzheimer's disease, and use it to predict the time to clinical onset of subjects carrying genetic mutation.

Role of 4-hydroxy-2-nonenal (HNE) in the pathogenesis of alzheimer disease and other selected age-related neurodegenerative disorders.

PubMed

Di Domenico, Fabio; Tramutola, Antonella; Butterfield, D Allan

2017-10-01

Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered membrane permeability and eventual cell death. Moreover, the peroxidation of polyunsaturated fatty acids leads to the formation of aldehydes, which can act as toxic by-products. One of the most abundant and cytotoxic lipid -derived aldehydes is 4-hydroxy 2-nonenal (HNE). HNE toxicity is mainly due to the alterations of cell functions by the formation of covalent adducts of HNE with proteins. A key marker of lipid peroxidation, HNE-protein adducts, were found to be elevated in brain tissues and body fluids of Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis subjects and/or models of the respective age-related neurodegenerative diseases. Although only a few proteins were identified as common targets of HNE modification across all these listed disorders, a high overlap of these proteins occurs concerning the alteration of common pathways, such as glucose metabolism or mitochondrial function that are known to contribute to cognitive decline. Within this context, despite the different etiological and pathological mechanisms that lead to the onset of different neurodegenerative diseases, the formation of HNE-protein adducts might represent the shared leit-motif, which aggravates brain damage contributing to disease specific clinical presentation and decline in cognitive performance observed in each case. Copyright © 2016 Elsevier Inc. All rights reserved.

Dysthymic disorder: clinical characteristics in relation to age at onset.

PubMed

Barzega, G; Maina, G; Venturello, S; Bogetto, F

2001-09-01

The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. The study is retrospective and enrolls a limited number of cases. The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.

A preliminary study of the influence of age of onset and childhood trauma on cortical thickness in major depressive disorder.

PubMed

Jaworska, Natalia; MacMaster, Frank P; Gaxiola, Ismael; Cortese, Filomeno; Goodyear, Bradley; Ramasubbu, Rajamannar

2014-01-01

Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Adults with MDD (N=36) and controls (HC; N=18) underwent magnetic resonance imaging. Twenty patients had MDD onset<24 years of age (pediatric onset) and 16 had onset>25 years of age (adult onset). The MDD group was also subdivided into those with (N=12) and without (N=19) physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

PubMed

Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A

2010-03-01

Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.

Early-Onset Psychoses: Comparison of Clinical Features and Adult Outcome in 3 Diagnostic Groups

ERIC Educational Resources Information Center

Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

2009-01-01

A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a…

Biological insight, high-throughput datasets and the nature of neuro-degenerative disorders.

PubMed

Valente, André X C N; Oliveira, Paulo J; Khaiboullina, Svetlana F; Palotás, András; Rizvanov, Albert A

2013-09-01

Life sciences are experiencing a historical shift towards a quantitative, data-rich regime. This transition has been associated with the advent of bio-informatics: mathematicians, physicists, computer scientists and statisticians are now commonplace in the field, working on the analysis of ever larger data-sets. An open question regarding what should drive scientific progress in this new era remains: will biological insight become increasingly irrelevant in a world of hypothesis-free, unbiased data analysis? This piece offers a different perspective, pin-pointing that biological thought is more-than-ever relevant in a data-rich setting. Some of the novel highthroughput information being acquired in the field of neuro-degenerative disorders is highlighted here. As but one example of how theory and experiment can interact in this new reality, our efforts in developing an idiopathic neuro-degenerative disease hematopoietic stemcell ageing theory are described.

Mood disorders in eating disorder patients: Prevalence and chronology of ONSET.

PubMed

Godart, N; Radon, L; Curt, F; Duclos, J; Perdereau, F; Lang, F; Venisse, J L; Halfon, O; Bizouard, P; Loas, G; Corcos, M; Jeammet, Ph; Flament, M F

2015-10-01

In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control group matched for age and gender. The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Transgenic Mouse Models of Childhood Onset Psychiatric Disorders

PubMed Central

Robertson, Holly R.; Feng, Guoping

2011-01-01

Childhood onset psychiatric disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Mood Disorders, Obsessive Compulsive Spectrum Disorders (OCSD), and Schizophrenia (SZ), affect many school age children leading to a lower quality of life, including difficulties in school and personal relationships that persists into adulthood. Currently, the causes of these psychiatric disorders are poorly understood resulting in difficulty diagnosing affected children, and insufficient treatment options. Family and twin studies implicate a genetic contribution for ADHD, ASD, Mood Disorders, OCSD, and SZ. Identification of candidate genes and chromosomal regions associated with a particular disorder provide targets for directed research, and understanding how these genes influence the disease state will provide valuable insights for improving the diagnosis and treatment of children with psychiatric disorders. Animal models are one important approach in the study of human diseases, allowing for the use of a variety of experimental approaches to dissect the contribution of a specific chromosomal or genetic abnormality in human disorders. While it is impossible to model an entire psychiatric disorder in a single animal model, these models can be extremely valuable in dissecting out the specific role of a gene, pathway, neuron subtype, or brain region in a particular abnormal behavior. In this review we discuss existing transgenic mouse models for childhood onset psychiatric disorders. We compare the strength and weakness of various transgenic animal models proposed for each of the common childhood onset psychiatric disorders, and discuss future directions for the study of these disorders using cutting-edge genetic tools. PMID:21309772

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PubMed

Sanchez, Lauren A; Maggadottir, Solrun Melkorka; Pantell, Matthew S; Lugar, Patricia; Rundles, Charlotte Cunningham; Sullivan, Kathleen E

2017-08-01

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for

Stroke and neurodegenerative disorders. 3. Stroke: rehabilitation management.

PubMed

Bogey, Ross A; Geis, Carolyn C; Bryant, Phillip R; Moroz, Alex; O'neill, Bryan J

2004-03-01

This self-directed learning module highlights common rehabilitation issues in stroke survivors. Topics include spasticity, constraint-induced movement therapy, partial body weight-supported treadmill training, virtual reality training, vestibular retraining, aphasia treatment, and cognitive retraining. It is part of the study chapter on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. (a) To identify and review the treatment options for poststroke spasticity; (b) to review the use of body weight-supported treadmill training in stroke patients; (c) to describe virtual reality training as an adjunct in stroke rehabilitation; (d) to review vestibular rehabilitation; (e) to discuss advances in aphasia treatment; (f) to discuss cognitive retraining; and (g) to provide an update on treatment of neglect syndromes.

Early onset obsessive-compulsive disorder with and without tics.

PubMed

de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

2009-07-01

Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

In Vitro Microfluidic Models for Neurodegenerative Disorders.

PubMed

Osaki, Tatsuya; Shin, Yoojin; Sivathanu, Vivek; Campisi, Marco; Kamm, Roger D

2018-01-01

Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progressive and self-limiting neurodegenerative disorders in Africa: a new prominent field of research led by South Africa but without strong health policy.

PubMed

Poreau, Brice

2016-01-01

Neurodegenerative disorders are involved in mortality and morbidity of every country. A high prevalence is estimated in Africa. Neurodegenerative disorders are defined by a progressive or self-limiting alteration of neurons implied in specific functional and anatomical functions. It encompasses a various range of clinical disorders from self-limiting to progressive. Focus on public health policies and scientific research is needed to understand the mechanisms to reduce this high prevalence. We use bibliometrics and mapping tools to explore the area studies and countries involved in scientific research on neurodegenerative disorders in Africa. We used two databases: Web of Science and Pubmed. We analyzed the journals, most cited articles, authors, publication years, organizations, funding agencies, countries and keywords in Web of Science Core collection database and publication years and Medical Subject Headings in Pubmed database. We mapped the data using VOSviewer. We accessed 44 articles published between 1975 and 2014 in Web of Science Core collection Database and 669 from Pubmed database. The majority of which were after 2006. The main countries involved in research on neurodegenerative disorders in Africa the USA, the United Kingdom, France and South Africa representing the main network collaboration. Clinical neurology and Genetics hereditary are the main Web of Science categories whereas Neurosciences and Biochemistry and Molecular Biology are the main Web of Science categories for the general search "neurodegenerative disorders" not restrained to Africa. This is confirmed by Medical Subject Headings analysis from Pubmed with one more area study: Treatment. Neurodegenerative disorders research is leaded by South Africa with a network involving the USA, the UK, as well as African countries such Zambia. The chief field that emerged was on patient and hereditary as well as treatment. Public health policies were lacking fields in research whereas prevalence is

Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control

PubMed Central

Bächle, Christina; Lange, Karin; Stahl-Pehe, Anna; Castillo, Katty; Scheuing, Nicole; Holl, Reinhard W.; Giani, Guido; Rosenbauer, Joachim

2015-01-01

Background This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. Methods In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. Results A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, p<0.001). However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006). Conclusions Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes. PMID:26121155

Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control.

PubMed

Bächle, Christina; Lange, Karin; Stahl-Pehe, Anna; Castillo, Katty; Scheuing, Nicole; Holl, Reinhard W; Giani, Guido; Rosenbauer, Joachim

2015-01-01

This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, p<0.001). However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006). Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.

Mitochondrial medicine for neurodegenerative diseases.

PubMed

Du, Heng; Yan, Shirley ShiDu

2010-05-01

Mitochondrial dysfunction has been reported in a wide array of neurological disorders ranging from neuromuscular to neurodegenerative diseases. Recent studies on neurodegenerative diseases have revealed that mitochondrial pathology is generally found in inherited or sporadic neurodegenerative diseases and is believed to be involved in the pathophysiological process of these diseases. Commonly seen types of mitochondrial dysfunction in neurodegenerative diseases include excessive free radical generation, lowered ATP production, mitochondrial permeability transition, mitochondrial DNA lesions, perturbed mitochondrial dynamics and apoptosis. Mitochondrial medicine as an emerging therapeutic strategy targeted to mitochondrial dysfunction in neurodegenerative diseases has been proven to be of value, though this area of research is still at in its early stage. In this article, we report on recent progress in the development of several mitochondrial therapies including antioxidants, blockade of mitochondrial permeability transition, and mitochondrial gene therapy as evidence that mitochondrial medicine has promise in the treatment of neurodegenerative diseases. 2010 Elsevier Ltd. All rights reserved.

[MicroRNA in neurodegenerative disorders].

PubMed

Sobue, Gen

2013-01-01

MicroRNAs (miRNAs) bind to the 3'-untranslated region of mRNA, and thereby suppress the gene expression. Recent studies suggest that miRNAs modify the pathogenesis of cancer and neurodegeneration. Our study demonstrated that the expression levels of miR-196a is increased in a mouse model of spinal and bulbar muscular atrophy (SBMA), a neurodegenerative disease caused by the expansion of polyglutamine in androgen receptor (AR). In cultured neuronal cells, miR-196a decayed the mutant AR mRNA via silencing CUG triplet repeat RNA binding protein 2, a potent miR-196a targeting mRNA, which contributed to stabilize the mutant AR mRNA. Adeno-associated virus vector-mediated delivery of this miRNA attenuates the expression of the mutant AR, resulting in the mitigation of motor neuron degeneration in the SBMA mice. Introduction of miRNA appears to be a novel therapeutic strategy for devastating neurodegenerative diseases.

Associations between DSM-IV mental disorders and subsequent heart disease onset: beyond depression.

PubMed

Scott, Kate M; de Jonge, Peter; Alonso, Jordi; Viana, Maria Carmen; Liu, Zhaorui; O'Neill, Siobhan; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Stein, Dan J; de Girolamo, Giovanni; Florescu, Silvia E; Hu, Chiyi; Taib, Nezar Ismet; Lépine, Jean-Pierre; Levinson, Daphna; Matschinger, Herbert; Medina-Mora, Maria Elena; Piazza, Marina; Posada-Villa, José A; Uda, Hidenori; Wojtyniak, Bogdan J; Lim, Carmen C W; Kessler, Ronald C

2013-10-15

Prior studies on the depression-heart disease association have not usually used diagnostic measures of depression, or taken other mental disorders into consideration. As a result, it is not clear whether the association between depression and heart disease onset reflects a specific association, or the comorbidity between depression and other mental disorders. Additionally, the relative magnitude of associations of a range of mental disorders with heart disease onset is unknown. Face-to-face household surveys were conducted in 19 countries (n=52,095; person years=2,141,194). The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Heart disease was indicated by self-report of physician's diagnosis, or self-report of heart attack, together with their timing (year). Survival analyses estimated associations between first onset of mental disorders and subsequent heart disease onset. After comorbidity adjustment, depression, panic disorder, specific phobia, post-traumatic stress disorder and alcohol use disorders were associated with heart disease onset (ORs 1.3-1.6). Increasing number of mental disorders was associated with heart disease in a dose-response fashion. Mood disorders and alcohol abuse were more strongly associated with earlier onset than later onset heart disease. Associations did not vary by gender. Depression, anxiety and alcohol use disorders were significantly associated with heart disease onset; depression was the weakest predictor. If confirmed in future prospective studies, the breadth of psychopathology's links with heart disease onset has substantial clinical and public health implications. © 2013.

Associations between DSM-IV mental disorders and subsequent heart disease onset: beyond depression

PubMed Central

Scott, Kate M.; de Jonge, Peter; Alonso, Jordi; Viana, Maria Carmen; Liu, Zhaorui; O’Neill, Siobhan; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Stein, Dan J.; de Girolamo, Giovanni; Florescu, Silvia E.; Hu, Chiyi; Taib, Nezar Ismet; Lépine, Jean-Pierre; Levinson, Daphna; Matschinger, Herbert; Medina-Mora, Maria Elena; Piazza, Marina; Posada-Villa, José A.; Uda, Hidenori; Wojtyniak, Bogdan J.; Lim, Carmen C. W.; Kessler, Ronald C.

2013-01-01

Background Prior studies on the depression-heart disease association have not usually used diagnostic measures of depression, nor taken other mental disorders into consideration. As a result, it is not clear whether the association between depression and heart disease onset reflects a specific association, or the comorbidity between depression and other mental disorders. Additionally, the relative magnitude of associations of a range of mental disorders with heart disease onset is unknown. Methods Face-to-face household surveys were conducted in 19 countries (n=52,095; person years=2,141,194). The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Heart disease was indicated by self-report of physician’s diagnosis, or self-report of heart attack, together with their timing (year). Survival analyses estimated associations between first onset of mental disorders and subsequent heart disease onset. Results After comorbidity adjustment, depression, panic disorder, specific phobia, post-traumatic stress disorder and alcohol use disorders were associated with heart disease onset (ORs 1.3–1.6). Increasing number of mental disorders was associated with heart disease in a dose-response fashion. Mood disorders and alcohol abuse were more strongly associated with earlier onset than later onset heart disease. Associations did not vary by gender. Conclusions Depression, anxiety and alcohol use disorders were significantly associated with heart disease onset; depression was the weakest predictor. If confirmed in future prospective studies, the breadth of psychopathology’s links with heart disease onset has substantial clinical and public health implications. PMID:23993321

Is adolescent-onset first-episode psychosis different from adult onset?

PubMed

Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-08-01

To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated psychosis, diagnosis, length of prodromal period, premorbid adjustment, level of psychotic, negative, depressive, anxiety, and extrapyramidal symptoms, and alcohol and drug use. Eighty-two patients (40.8%) had an onset of psychosis during adolescence (ages 15-18) and 119 (59.2%) during young adulthood (ages 19-30). The adolescent-onset group experienced longer delays in treatment of psychosis (duration of untreated psychosis) (p < .02), showed modestly worse premorbid functioning during late adolescence (p < .05), and were more likely to present with bizarre behavior (p < .01) and primary negative symptoms (p < .01). Patients with adolescent onset of psychosis are more likely to present with clinical characteristics that portend a poorer outcome and may require a different approach to early identification and treatment.

Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.

PubMed

Koric, L; Guedj, E; Habert, M O; Semah, F; Branger, P; Payoux, P; Le Jeune, F

2016-12-01

The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition. According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias. The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders

PubMed Central

de Pedro-Cuesta, Jesús; Martínez-Martín, Pablo; Rábano, Alberto; Alcalde-Cabero, Enrique; José García López, Fernando; Almazán-Isla, Javier; Ruiz-Tovar, María; Medrano, Maria-José; Avellanal, Fuencisla; Calero, Olga; Calero, Miguel

2016-01-01

Background: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific “drivers”, i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities. Objectives and Methods: Redefining drivers as “neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms”, we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns. Results: We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson’s disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer’s disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus. Conclusion: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these. PMID:26923014

Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

PubMed

Luan, Hemi; Wang, Xian; Cai, Zongwei

2017-11-12

Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the

Depressive symptoms in neurodegenerative diseases

PubMed Central

Baquero, Miquel; Martín, Nuria

2015-01-01

Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment. PMID:26301229

Obstructive sleep apnea and neurodegenerative diseases: A bidirectional relation

PubMed Central

Bahia, Christianne Martins Corrêa da Silva; Pereira, João Santos

2015-01-01

Sleep disorders are common during the clinical course of the main neurodegenerative diseases. Among these disorders, obstructive sleep apnea has been extensively studied in the last decade and recent knowledge regarding its relationship with the neurodegenerative process points a bidirectional relationship. Neurodegenerative diseases can lead to functional changes in the respiratory system that facilitate the emergence of apnea. On the other hand, obstructive sleep apnea itself can lead to acceleration of neuronal death due to intermittent hypoxia. Considering that obstructive sleep apnea is a potentially treatable condition, its early identification and intervention could have a positive impact on the management of patients with neurodegenerative diseases. PMID:29213936

Epigenetic Research of Neurodegenerative Disorders Using Patient iPSC-Based Models

PubMed Central

2016-01-01

Epigenetic mechanisms play a role in human disease but their involvement in pathologies from the central nervous system has been hampered by the complexity of the brain together with its unique cellular architecture and diversity. Until recently, disease targeted neural types were only available as postmortem materials after many years of disease evolution. Current in vitro systems of induced pluripotent stem cells (iPSCs) generated by cell reprogramming of somatic cells from patients have provided valuable disease models recapitulating key pathological molecular events. Yet whether cell reprogramming on itself implies a truly epigenetic reprogramming, the epigenetic mechanisms governing this process are only partially understood. Moreover, elucidating epigenetic regulation using patient-specific iPSC-derived neural models is expected to have a great impact to unravel the pathophysiology of neurodegenerative diseases and to hopefully expand future therapeutic possibilities. Here we will critically review current knowledge of epigenetic involvement in neurodegenerative disorders focusing on the potential of iPSCs as a promising tool for epigenetic research of these diseases. PMID:26697081

Differences in Long-Term Disease Activity and Treatment of Adult Patients With Childhood-and Adult-Onset Systemic Lupus Erythematosus

PubMed Central

Hersh, Aimee O.; von Scheven, Emily; Yazdany, Jinoos; Panopalis, Pantelis; Trupin, Laura; Julian, Laura; Katz, Patricia; Criswell, Lindsey A.; Yelin, Edward

2009-01-01

Objective To compare differences in long-term outcome between adults with childhood-onset (age at diagnosis <18 years) systemic lupus erythematosus (SLE) and with adult-onset SLE. Methods Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 885 adult subjects with SLE (90 childhood-onset [cSLE], 795 adult-onset [aSLE]). Baseline and 1-year followup data were obtained via structured 1-hour telephone interviews conducted between 2002 and 2006. Using self-report data, differences in organ involvement and disease morbidity, current disease status and activity, past and current medication use, and number of physician visits were compared, based on age at diagnosis of SLE. Results Average disease duration for the cSLE and aSLE subgroups was 16.5 and 13.4 years, respectively, and mean age at followup was 30.5 and 49.9 years, respectively. When compared with aSLE subjects, cSLE subjects had a higher frequency of SLE-related renal disease, whereas aSLE subjects were more likely to report a history of pulmonary disease. Rates of clotting disorders, seizures, and myocardial infarction were similar between the 2 groups. At followup, cSLE subjects had lower overall disease activity, but were more likely to be taking steroids and other immunosuppressive therapies. The total number of yearly physician visits was similar between the 2 groups, although cSLE subjects had a higher number of nephrology visits. Conclusion This study demonstrates important differences in the outcomes of patients with cSLE and aSLE, and provides important prognostic information about long-term SLE disease activity and treatment. PMID:19116979

The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders.

PubMed

Smith, Derek K; He, Miao; Zhang, Chun-Li; Zheng, Jialin C

2017-10-01

Neural cell identity reprogramming strategies aim to treat age-related neurodegenerative disorders with newly induced neurons that regenerate neural architecture and functional circuits in vivo. The isolation and neural differentiation of pluripotent embryonic stem cells provided the first in vitro models of human neurodegenerative disease. Investigation into the molecular mechanisms underlying stem cell pluripotency revealed that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs) and these cells could be used to model Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease. Additional neural precursor and direct transdifferentiation strategies further enabled the induction of diverse neural linages and neuron subtypes both in vitro and in vivo. In this review, we highlight neural induction strategies that utilize stem cells, iPSCs, and lineage reprogramming to model or treat age-related neurodegenerative diseases, as well as, the clinical challenges related to neural transplantation and in vivo reprogramming strategies. Copyright © 2016. Published by Elsevier Ltd.

The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders

PubMed Central

Smith, Derek K.; He, Miao; Zhang, Chun-Li; Zheng, Jialin C.

2018-01-01

Neural cell identity reprogramming strategies aim to treat age-related neurodegenerative disorders with newly induced neurons that regenerate neural architecture and functional circuits in vivo. The isolation and neural differentiation of pluripotent embryonic stem cells provided the first in vitro models of human neurodegenerative disease. Investigation into the molecular mechanisms underlying stem cell pluripotency revealed that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs) and these cells could be used to model Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease. Additional neural precursor and direct transdifferentiation strategies further enabled the induction of diverse neural linages and neuron subtypes both in vitro and in vivo. In this review, we highlight neural induction strategies that utilize stem cells, iPSCs, and lineage reprogramming to model or treat age-related neurodegenerative diseases, as well as, the clinical challenges related to neural transplantation and in vivo reprogramming strategies. PMID:26844759

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

PubMed Central

Chin-Chan, Miguel; Navarro-Yepes, Juliana; Quintanilla-Vega, Betzabet

2015-01-01

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action. PMID:25914621

Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support.

PubMed

Marsh, Samuel E; Blurton-Jones, Mathew

2017-06-01

Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease currently affect tens of millions of people worldwide. Unfortunately, as the world's population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders. A growing number of pre-clinical studies have suggested that transplantation of neural stem cells (NSCs) could offer a promising new therapeutic approach for neurodegeneration. While much of the initial excitement about this strategy focused on the use of NSCs to replace degenerating neurons, more recent studies have implicated NSC-mediated changes in neurotrophins as a major mechanism of therapeutic efficacy. In this mini-review we will discuss recent work that examines the ability of NSCs to provide trophic support to disease-effected neuronal populations and synapses in models of neurodegeneration. We will then also discuss some of key challenges that remain before NSC-based therapies for neurodegenerative diseases can be translated toward potential clinical testing. Copyright © 2017 Elsevier Ltd. All rights reserved.

A 12-year prognosis of adult-onset asthma: Seinäjoki Adult Asthma Study.

PubMed

Tuomisto, Leena E; Ilmarinen, Pinja; Niemelä, Onni; Haanpää, Jussi; Kankaanranta, Terhi; Kankaanranta, Hannu

2016-08-01

Long-term prognosis of adult-onset asthma is poorly known. To evaluate 12-year prognosis of adult-onset asthma and the factors associated with disease prognosis. Seinäjoki Adult-onset Asthma Study (SAAS) is a 12-year real-life single-center follow-up study of new-onset asthma diagnosed at adult age and treated in primary and specialized care. Remission was defined by no symptoms and no asthma medication use for 6 months. Asthma control was evaluated according to Global Initiative for Asthma 2010. Factors associated with current asthma control were analyzed by multinomial multivariate logistic regression. A total of 203 patients (79% of the baseline population) were followed for 12 years. Remission occurred in 6 (3%) patients. In 34% asthma was controlled, in 36% it was partially controlled and in 30% uncontrolled. Uncontrolled asthma was predicted by elevated body-mass index at baseline, smoking (pack-years) and current allergic or persistent rhinitis. Elevated blood eosinophils and good lung function (FEV1) at baseline protected from uncontrolled asthma. In contrast, gender, age at the onset or baseline symptoms (Airways Questionnaire 20) were not significant predictors of uncontrolled disease. During a 12-year follow-up, remission of adult-onset asthma was rare occurring in only 3% of patients. The majority of patients (66%) presented either with uncontrolled or partially controlled asthma. This study is registered at ClinicalTrials.gov with identifier number NCT02733016. Copyright © 2016 Elsevier Ltd. All rights reserved.

Social Integration in Young Adulthood and the Subsequent Onset of Substance Use and Disorders among a Community Population of Urban African Americans*

PubMed Central

Green, Kerry M.; Doherty, Elaine E.; Reisinger, Heather S.; Chilcoat, Howard D.; Ensminger, Margaret

2009-01-01

Aims This article examines the association between social integration in young adulthood and the later onset of substance use and disorders through mid-adulthood. Design Data come from a community cohort of African Americans followed longitudinally from age 6–42 with four assessment periods. Setting The cohort all lived in the Woodlawn neighborhood of Chicago in 1966, an urban disadvantaged setting. Participants All Woodlawn first graders in 1966 were asked to participate; 13 families declined (N=1242). Measurement Substance use was measured via interview at age 42 and includes the onset of alcohol and drug use disorders and the onset of cocaine/heroin use between ages 32 and 42. Social integration measures were assessed via interview at age 32 and include social roles (employee, spouse, parent), participation in religious and social organizations, and a measure of overall social integration. Control variables were measured in childhood and later in the lifecourse. Findings Multivariate regression analyses suggest that unemployment, being unmarried, infrequent religious service attendance, and lower overall social integration in young adulthood predict later adult-onset drug use disorders, but not alcohol use disorders once confounders are taken into consideration. Unemployment and lower overall social integration predict onset of cocaine/heroin use later in adulthood. Conclusions Results show meaningful onset of drug use and substance use disorders during mid-adulthood and that social integration in young adulthood seems to play a role in later onset of drug use and drug disorders, but not alcohol disorders. PMID:20402992

Suicidality in adolescents and adults with binge-eating disorder: Results from the national comorbidity survey replication and adolescent supplement.

PubMed

Forrest, Lauren N; Zuromski, Kelly L; Dodd, Dorian R; Smith, April R

2017-01-01

The relation between binge-eating disorder (BED) and suicidality (i.e., suicide ideation, plan, and/or attempt) has not been studied extensively, and it is unknown whether BED is uniquely associated with suicidality when adjusting for comorbid psychopathology. Moreover, the course of suicidality in BED has not been determined and it is unknown whether BED precedes suicidality or vice versa. A total of 10,123 adolescents and 2,980 adults from two nationally representative surveys were administered diagnostic interviews assessing psychopathology and suicidality, as well the retrospectively reported ages of onset. Among adults and adolescents, BED was associated with elevated odds of suicide ideation, plan, and attempt at a univariate level, but BED was not associated with elevated odds of suicidality when adjusting for comorbid psychopathology. Kaplan-Meier estimates of temporal patterns displayed that most adolescents experienced suicidality onset following BED onset, whereas most adults experienced suicidality onset prior to BED onset. BED, comorbid disorders, and suicidality share common factors and interrelations, and individuals with BED and comorbid disorders may be at particularly high risk for suicidal outcomes. The presence of BED in adolescence may serve as a marker for more severe symptomatology that precedes the occurrence of suicidality. Research is needed to understand how eating disorder symptoms, comorbid symptoms, and suicidality affect one another over time. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2017; 50:40-49). © 2016 Wiley Periodicals, Inc.

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

PubMed

Fagherazzi, Elen V; Garcia, Vanessa A; Maurmann, Natasha; Bervanger, Thielly; Halmenschlager, Luis H; Busato, Stefano B; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Schröder, Nadja

2012-02-01

Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

Age of onset and temporal sequencing of lifetime DSM-IV alcohol use disorders relative to comorbid mood and anxiety disorders.

PubMed

Falk, Daniel E; Yi, Hsiao-Ye; Hilton, Michael E

2008-04-01

Understanding the temporal sequencing of alcohol use disorders (AUDs) and comorbid mood and anxiety disorders may help to disentangle the etiological underpinnings of comorbidity. Methodological limitations of previous studies, however, may have led to inconsistent or inconclusive findings. To describe the temporal sequencing of the onset of AUDs relative to the onset of specific comorbid mood and anxiety disorders using a large, nationally representative survey. AUD onset tended to follow the onset of 2 of the 9 mood and anxiety disorders (specific and social phobia). The onset of alcohol abuse tended to precede the onset of 5 of the 9 mood and anxiety disorders (GAD, panic, panic with agoraphobia, major depression, and dysthymia), whereas the onset of alcohol dependence tended to precede the onset of only 2 of the 9 mood and anxiety disorders (GAD and panic). Lag times between primary and subsequent disorders generally ranged from 7 to 16 years. Comorbid individuals whose alcohol dependence came after panic with agoraphobia, hypomania, and GAD had increased risk of persistent alcohol dependence. Alcohol abuse, but not dependence, precedes many mood and anxiety disorders. If the primary disorder does in fact play a causative or contributing role in the development of the subsequent disorder, this role can best be described as "temporally distal." However, in assessing the risk for persistent alcohol dependence, clinicians should not only consider the type of comorbid mood/anxiety disorder, but also the temporal ordering of these disorders.

Integration of Nanobots Into Neural Circuits As a Future Therapy for Treating Neurodegenerative Disorders.

PubMed

Saniotis, Arthur; Henneberg, Maciej; Sawalma, Abdul-Rahman

2018-01-01

Recent neuroscientific research demonstrates that the human brain is becoming altered by technological devices. Improvements in biotechnologies and computer based technologies are now increasing the likelihood for the development of brain augmentation devices in the next 20 years. We have developed the idea of an "Endomyccorhizae like interface" (ELI) nanocognitive device as a new kind of future neuroprosthetic which aims to facilitate neuronal network properties in individuals with neurodegenerative disorders. The design of our ELI may overcome the problems of invasive neuroprosthetics, post-operative inflammation, and infection and neuroprosthetic degradation. The method in which our ELI is connected and integrated to neuronal networks is based on a mechanism similar to endomyccorhizae which is the oldest and most widespread form of plant symbiosis. We propose that the principle of Endomyccorhizae could be relevant for developing a crossing point between the ELI and neuronal networks. Similar to endomyccorhizae the ELI will be designed to form webs, each of which connects multiple neurons together. The ELI will function to sense action potentials and deliver it to the neurons it connects to. This is expected to compensate for neuronal loss in some neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

Developmental differences according to age at onset in juvenile bipolar disorder.

PubMed

Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Toni, Cristina; Bertini, Nicoletta; Pfanner, Chiara; Berloffa, Stefano; Pari, Cinzia

2006-12-01

This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

Body height and weight of patients with childhood onset and adult onset thyrotoxicosis.

PubMed

Takamatsu, J; Kobe, N; Ito, M; Ohsawa, N

1999-03-01

The present study has compared body height and weight of thyrotoxic female patients of childhood onset and adult onset. The body height of 141 out of 143 (99%) adult-onset thyrotoxic patients was within the range of mean +/- 2SD for the age-matched general Japanese female population. On the other hand, in 42 patients with childhood-onset thyrotoxicosis, 6 (14%) had their height being greater than the mean + 2SD of general population, and 34 (81%) were taller than the mean value. In 86 patients with siblings, 42 (49%) were at least 2 cm taller than their sisters, and 26 (30%) were more than 2 cm shorter than their sisters. The body weight of 27 out of 42 (68%) patients younger than 20 years was not decreased but was even greater than the mean value for the age-matched general population. The results indicate that excessive thyroid hormone in vivo enhances body height in humans. The increased body weight in some young patients suggests that enhanced dietary intake due to increased appetite in hyperthyroidism has overcome the energy loss with increased metabolism.

Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Blandizzi, Corrado; Fornai, Matteo

2018-05-24

Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.

Oxidative Stress and Neurodegenerative Disorders

PubMed Central

Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

2013-01-01

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

Glutamate and Neurodegenerative Disease

NASA Astrophysics Data System (ADS)

Schaeffer, Eric; Duplantier, Allen

As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

PubMed

Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

2010-08-01

The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Niemann-Pick Disease Type C Presenting as a Developmental Coordination Disorder with Bullying by Peers in a School-Age Child.

PubMed

Suzuki, Ryo; Tanaka, Atsushi; Matsui, Toshiharu; Gunji, Tetsuki; Tohyama, Jun; Nairita, Aya; Nanba, Eiji; Ohno, Kousaku

2015-01-01

Niemann-Pick disease type C (NPC) is a rare progressive neurodegenerative disorder, often with onset after normal early childhood development. Juvenile onset NPC patients slowly develop cerebellar symptoms and cognitive impairment and often experience difficulties at school. However, these problems may be overlooked due to the unpublicized nature of NPC, given that it is a rare metabolic disorder. In this report, we present an 11-year-old male NPC patient, who suffered from clumsiness and difficulties in attention and academic and social skills. His symptoms were initially considered to be due to developmental coordination disorder (DCD) coexisting with bullying by peers. DCD is a type of neurodevelopmental disorder defined according to DSM-IV and is characterized by clumsiness that interferes with academic achievement and social integration not due to other general medical conditions. However, a detailed investigation of the patient suggested that the problems could be attributed to the onset of NPC. Clinicians should keep neurodegenerative disorders as differential diagnosis of children with multiple school problems.

Obsessive-compulsive disorder and the risk of subsequent mental disorders: A community study of adolescents and young adults.

PubMed

Hofer, Patrizia D; Wahl, Karina; Meyer, Andrea H; Miché, Marcel; Beesdo-Baum, Katja; Wong, Shiu F; Grisham, Jessica R; Wittchen, Hans-Ulrich; Lieb, Roselind

2018-04-01

Comorbidity of obsessive-compulsive disorder (OCD) with other mental disorders has been demonstrated repeatedly. Few longitudinal studies, however, have evaluated the temporal association of prior OCD and subsequent mental disorders across the age period of highest risk for first onset of mental disorders. We examined associations between prior OCD and a broad range of subsequent mental disorders and simulated proportions of new onsets of mental disorders that could potentially be attributed to prior OCD, assuming a causal relationship. Data from 3,021 14- to 24-year-old community subjects were prospectively collected for up to 10 years. DSM-IV OCD and other DSM-IV mental disorders were assessed with the Munich-Composite International Diagnostic Interview. We used adjusted time-dependent proportional hazard models to estimate the temporal associations of prior OCD with subsequent mental disorders. Prior OCD was associated with an increased risk of bipolar disorders (BIP; [hazard ratio, HR = 6.9, 95% confidence interval, CI, (2.8,17.3)], bulimia nervosa [HR = 6.8 (1.3,36.6)], dysthymia [HR = 4.4 (2.1,9.0)], generalized anxiety disorder (GAD; [HR = 3.4 (1.1,10.9)], and social phobia [HR = 2.9 (1.1,7.7)]). Of these outcome disorders, between 65 and 85% could be attributed to OCD in the exposed group, whereas between 1.5 and 7.7% could be attributed to OCD in the total sample. This study provides strong evidence that prior OCD is associated with an increased risk of subsequent onset of BIP, bulimia nervosa, dysthymia, GAD, and social phobia among adolescents and young adults. Future studies should evaluate if early treatment of OCD can prevent the onset of these subsequent mental disorders. © 2018 Wiley Periodicals, Inc.

Variation in Genes Related to Cochlear Biology Is Strongly Associated with Adult-Onset Deafness in Border Collies

PubMed Central

Ruhe, Alison L.; Erdman, Carolyn A.; Robertson, Kathryn R.; Webb, Aubrey A.; Williams, D. Colette; Chang, Melanie L.; Hytönen, Marjo K.; Lohi, Hannes; Hamilton, Steven P.; Neff, Mark W.

2012-01-01

Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3–5 years) than typically expected for aging dogs (8–10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09×10−13). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS–guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders. PMID:23028339

Childhood-Onset Bipolar Disorder: Evidence for Increased Familial Loading of Psychiatric Illness

ERIC Educational Resources Information Center

Rende, Richard; Birmaher, Boris; Axelson, David; Strober, Michael; Gill, Mary Kay; Valeri, Sylvia; Chiappetta, Laurel; Ryan, Neal; Leonard, Henrietta; Hunt, Jeffrey; Iyengar, Satish; Keller, Martin

2007-01-01

Objective: To determine whether childhood-onset bipolar disorder (BP) is associated with an increased psychiatric family history compared with adolescent-onset BP. Method: Semistructured psychiatric interviews were conducted for 438 youth with BP spectrum disorders. To evaluate the effects of age at onset and psychiatric family history, the sample…

Predicting the onset of major depressive disorder and dysthymia in older adults with subthreshold depression: a community based study.

PubMed

Cuijpers, Pim; Beekman, Aartjan; Smit, Filip; Deeg, Dorly

2006-09-01

It is well-established that the incidence of major depressive disorder is increased in subjects with subthreshold depression. A new research area focuses on the possibilities of preventing the onset of major depressive disorders in subjects with subthreshold depression. An important research question for this research area is which subjects with subthreshold depression will develop a full-blown depressive disorder and which will not. We selected 154 older subjects with subthreshold depression (CES-D>16) but no DSM mood disorder from a longitudinal study among a large population based cohort aged between 55 and 85 years in The Netherlands. Of these subjects, 31 (20.1%) developed a mood disorder (major depression and/or dysthymia) at three-year or six-year follow-up. We examined risk factors and individual symptoms of mood disorder as predictors of onset of mood disorder. Two variables were found to be significant predictors in both bivariate and multivariate analyses: eating problems and sleep problems. The incidence of mood disorders differed strongly for different subpopulations, varying from 9% (for those not having any of the two risk factors) to 57% (for those having both risk factors). It appears to be possible to predict to a certain degree whether a subject with subthreshold depression will develop a mood disorder during the following years. Copyright (c) 2006 John Wiley & Sons, Ltd.

Adult-Onset NREM Parasomnia with Hypnopompic Hallucinatory Pain: A Case Report

PubMed Central

Mantoan, Laura; Eriksson, Sofia H.; Nisbet, Angus P.; Walker, Matthew C.

2013-01-01

We report the case of a 43-year-old woman presenting with nocturnal episodes of pain and screaming during sleep starting at age 30. There was no childhood or family history of parasomnia. The events had gradually become more frequent over the years, occurring in the first half of the night within 2 h of sleep onset. There were no triggers, and she had partial amnesia for the events. A diagnosis of adult-onset sleep terrors was made on clinical grounds and supported polysomnographically. Seizures and periodic limb movements were excluded as triggering factors. There was some mild sleep disordered breathing (predominantly non-desaturating hypopnea with a propensity for REM sleep of debatable significance). Imaging of the brain and spine and neurophysiological investigations ruled out lesions, entrapments, or neuropathies as possible causes of pain. Treatment (clonazepam, paroxetine, or gabapentin) was poorly tolerated and made no difference to the nocturnal episodes, while trazodone worsened them. This is the first report of hypnopompic psychic pain in association with a NREM parasomnia. We hypothesize that the pain may represent a sensory hallucination analogous to the more commonly recognized visual NREM parasomnia-associated hypnopompic visual hallucinations and that, as such, it may arise during arousal of the sensory neocortex as confabulatory response. Citation: Mantoan L; Eriksson SH; Nisbet AP; Walker MC. Adult-onset nrem parasomnia with hypnopompic hallucinatory pain: a case report. SLEEP 2013;36(2):287–290. PMID:23372277

Early-onset Major Depressive Disorder in men is associated with childlessness.

PubMed

Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

2010-07-01

The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat.

PubMed

Bowman, Elizabeth A; Velakoulis, Dennis; Desmond, Patricia; Walterfang, Mark

2018-01-01

Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.

IMPACT OF SPECIFIC PHOBIA ON THE RISK OF ONSET OF MENTAL DISORDERS: A 10-YEAR PROSPECTIVE-LONGITUDINAL COMMUNITY STUDY OF ADOLESCENTS AND YOUNG ADULTS.

PubMed

Lieb, Roselind; Miché, Marcel; Gloster, Andrew T; Beesdo-Baum, Katja; Meyer, Andrea H; Wittchen, Hans-Ulrich

2016-07-01

The role of specific phobia as a potentially important psychopathological precursor condition to more severe mental disorders is understudied. We examined the prospective-longitudinal association of early childhood/adolescent phobia with subsequent mental disorders and the proportion of outcome disease incidence attributable to specific phobia simultaneously for a broad range of disorders. N = 2210 14- to 24-year-old community subjects were followed up for 10 years. DSM-IV-specific phobia as exposure and a broad range of DSM-IV mental disorders as outcomes were assessed with the DSM-IV/M-CIDI. Logistic regressions, adjusting for confounders, were used to estimate the associations of specific phobia with the subsequent onset of outcome disorders. Baseline specific phobia predicted the subsequent first onset of anxiety disorders [panic disorder: risk ratio (RR) = 4.38, 95% confidence interval (2.34, 8.21); generalized anxiety disorder: RR = 4.10 (2.19, 7.69); posttraumatic stress disorder: RR = 2.15 (1.13, 4.10); obsessive-compulsive disorder: RR = 3.79 (1.63, 8.82)], affective disorders [major depression: RR = 1.54 (1.16, 2.03); bipolar disorder: RR = 2.20 (1.10, 4.41); dysthymia: RR = 2.75 (1.48, 5.11)], pain disorder: RR = 1.52 (1.14, 2.02), and eating disorders: RR = 2.27 (1.14, 4.51). Population attributable fractions (PAFs; i.e., proportion of outcome disease incidence in the total population attributable to specific phobia) were highest for panic disorder (PAF = 22.9), generalized anxiety disorder (PAF = 32.3), and obsessive-compulsive disorders (PAF = 30.2). This study provides strong evidence that specific phobia is an early onset disorder predicting the subsequent onset of a range of disorders. Future studies should examine the underlying mechanisms and the potential of using specific phobia as a target for prevention of subsequent psychopathology. © 2016 Wiley Periodicals, Inc.

Risk factors for secondary substance use disorders in people with childhood and adolescent-onset bipolar disorder: opportunities for prevention.

PubMed

Kenneson, Aileen; Funderburk, Jennifer S; Maisto, Stephen A

2013-07-01

Compared to other mental illnesses, bipolar disorder is associated with a disproportionately high rate of substance use disorders (SUDs), and the co-occurrence is associated with significant morbidity and mortality. Early diagnosis of primary bipolar disorder may provide opportunities for SUD prevention, but little is known about the risk factors for secondary SUD among individuals with bipolar disorder. The purposes of this study were to describe the population of people with childhood and adolescent-onset primary bipolar disorder, and to identify risk factors for secondary SUD in this population. Using data collected from the National Comorbidity Survey Replication study, we identified 158 individuals with childhood-onset (<13 years) or adolescent-onset (13-18 years) primary bipolar disorder (I, II or subthreshold). Survival analysis was used to identify risk factors for SUD. Compared to adolescent-onset, people with childhood-onset bipolar disorder had increased likelihoods of attention deficit hyperactivity disorder (ADHD) (adjusted odds ratio=2.81) and suicide attempt (aOR=3.61). Males were more likely than females to develop SUD, and did so at a faster rate. Hazard ratios of risk factors for SUD were: lifetime oppositional defiant disorder (2.048), any lifetime anxiety disorder (3.077), adolescent-onset bipolar disorder (1.653), and suicide attempt (15.424). SUD was not predicted by bipolar disorder type, family history of bipolar disorder, hospitalization for a mood episode, ADHD or conduct disorder. As clinicians struggle to help individuals with bipolar disorder, this study provides information that might be useful in identifying individuals at higher risk for SUD. Future research can examine whether targeting these risk factors may help prevent secondary SUD. Published by Elsevier Inc.

Treatment and outcome of adult-onset neuroblastoma.

PubMed

Suzuki, Maya; Kushner, Brian H; Kramer, Kim; Basu, Ellen M; Roberts, Stephen S; Hammond, William J; LaQuaglia, Michael P; Wolden, Suzanne L; Cheung, Nai-Kong V; Modak, Shakeel

2018-03-25

Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11 patients with locoregional disease, 10-year progression-free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti-GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5-year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long-term survival. Anti-GD2 immunotherapy was well tolerated and might be beneficial. © 2018 UICC.

Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

ERIC Educational Resources Information Center

Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

2010-01-01

Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

Anxiety and Related Disorders and Concealment in Sexual Minority Young Adults.

PubMed

Cohen, Jeffrey M; Blasey, Christine; Barr Taylor, C; Weiss, Brandon J; Newman, Michelle G

2016-01-01

Sexual minorities face greater exposure to discrimination and rejection than heterosexuals. Given these threats, sexual minorities may engage in sexual orientation concealment in order to avoid danger. This social stigma and minority stress places sexual minorities at risk for anxiety and related disorders. Given that three fourths of anxiety disorder onset occurs before the age of 24, the current study investigated the symptoms of generalized anxiety disorder, social phobia, panic disorder, posttraumatic stress disorder, and depression in sexual minority young adults relative to their heterosexual peers. Secondarily, the study investigated sexual orientation concealment as a predictor of anxiety and related disorders. A sample of 157 sexual minority and 157 heterosexual young adults matched on age and gender completed self-report measures of the aforementioned disorders, and indicated their level of sexual orientation concealment. Results revealed that sexual minority young adults reported greater symptoms relative to heterosexuals across all outcome measures. There were no interactions between sexual minority status and gender, however, women had higher symptoms across all disorders. Sexual minority young women appeared to be at the most risk for clinical levels of anxiety and related disorders. In addition, concealment of sexual orientation significantly predicted symptoms of social phobia. Implications are offered for the cognitive and behavioral treatment of anxiety and related disorders in this population. Copyright © 2015. Published by Elsevier Ltd.

Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia.

PubMed

Hohenbichler, Katharina; Lelotte, Julie; Lhommel, Renaud; Tahry, Riëm El; Vrielynck, Pascal; Santos, Susana Ferrao

2017-12-01

Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.

Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

PubMed Central

Luchowska-Kocot, Dorota; Kiełczykowska, Małgorzata; Musik, Irena; Kurzepa, Jacek

2017-01-01

Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders. PMID:28654017

Impact of sunlight on the age of onset of bipolar disorder

PubMed Central

Bauer, Michael; Glenn, Tasha; Alda, Martin; Andreassen, Ole A; Ardau, Raffaella; Bellivier, Frank; Berk, Michael; Bjella, Thomas D; Bossini, Letizia; Zompo, Maria Del; Dodd, Seetal; Fagiolini, Andrea; Frye, Mark A; Gonzalez-Pinto, Ana; Henry, Chantal; Kapczinski, Flávio; Kliwicki, Sebastian; König, Barbara; Kunz, Mauricio; Lafer, Beny; Lopez-Jaramillo, Carlos; Manchia, Mirko; Marsh, Wendy; Martinez-Cengotitabengoa, Mónica; Melle, Ingrid; Morken, Gunnar; Munoz, Rodrigo; Nery, Fabiano G; O’Donovan, Claire; Pfennig, Andrea; Quiroz, Danilo; Rasgon, Natalie; Reif, Andreas; Rybakowski, Janusz; Sagduyu, Kemal; Simhandl, Christian; Torrent, Carla; Vieta, Eduard; Zetin, Mark; Whybrow, Peter C

2012-01-01

Objective Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= −4.724, 95% CI: −8.124 to −1.323, p = 0.006), controlling for each country’s median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder. PMID:22612720

Induced Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Neurodegenerative Diseases.

PubMed

Cao, Lei; Tan, Lan; Jiang, Teng; Zhu, Xi-Chen; Yu, Jin-Tai

2015-08-01

Although most neurodegenerative diseases have been closely related to aberrant accumulation of aggregation-prone proteins in neurons, understanding their pathogenesis remains incomplete, and there is no treatment to delay the onset or slow the progression of many neurodegenerative diseases. The availability of induced pluripotent stem cells (iPSCs) in recapitulating the phenotypes of several late-onset neurodegenerative diseases marks the new era in in vitro modeling. The iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in these diseases and provides a novel human stem cell platform for screening new candidate therapeutics. Modeling human diseases using iPSCs has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. In this review, we introduce iPSC-based disease modeling in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In addition, we discuss the implementation of iPSCs in drug discovery associated with some new techniques.

Observing the onset of disability in older adults.

PubMed

Reynolds, Sandra L; Silverstein, Merril

2003-11-01

One of the greatest threats to the ability of older adults to live independently is the onset of disability in activities adults perform in their daily lives, such as dressing, eating, toileting, managing one's money, preparing meals and so on. This article examines the onset of disability in older adult Americans using three waves of the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey (1993, 1995, 1998; n=4228). We use medical/demographic factors (arthritis, heart disease, diabetes; age, gender, race/ethnicity, wealth), baseline characteristics (affect, cognition, health behaviors, medical insurance), and time-varying covariates (changes in chronic conditions and baseline characteristics) to predict the onset of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) disability, individually and in the aggregate, over time. We find the onset of ADL and IADL disability is a complex process, suggesting important roles for medical, demographic, social, psychological, and behavioral triggers, specifically negative affect, higher body weight, and by the lack of vigorous exercise. We also find that individual ADL and IADL impairments are predicted by a variety of different factors, suggesting that summary measures of disability may be masking a wealth of potentially useful interventions. In general, public health efforts in the area of controlling obesity and treating depressive symptoms should be supported.

Educational and vocational outcomes of adults with childhood- and adult-onset systemic lupus erythematosus: nine years of followup.

PubMed

Lawson, Erica F; Hersh, Aimee O; Trupin, Laura; von Scheven, Emily; Okumura, Megumi J; Yazdany, Jinoos; Yelin, Edward H

2014-05-01

To compare educational and vocational outcomes among adults with childhood-onset systemic lupus erythematosus (SLE) and adult-onset SLE. We used data derived from the 2002–2010 cycles of the Lupus Outcomes Study, a longitudinal cohort of 1,204 adult subjects with SLE. Subjects ages 18–60 years living in the US (n = 929) were included in the analysis and were classified as childhood-onset SLE if age at diagnosis was <18 years (n = 115). Logistic regression was used to assess the unadjusted and adjusted effect of childhood-onset SLE, sex, race/ethnicity, baseline age, urban or rural location, and US region on the likelihood of completing a bachelor's degree. Generalized estimating equations were used to assess the effect of childhood-onset SLE, demographics, education, and disease-related factors on the odds of employment, accounting for multiple observations over the study period. Subjects with childhood-onset SLE were on average younger (mean ± SD 29 ± 10 years versus 44 ± 9 years), with longer disease duration (mean ± SD 15 ± 10 years versus 11 ± 8 years). Subjects with adult-onset SLE and childhood-onset SLE subjects were equally likely to complete a bachelor's degree. However, subjects with childhood-onset SLE were significantly less likely to be employed, independent of demographic and disease characteristics (odds ratio 0.62, 95% confidence interval 0.42–0.91). While subjects with SLE are just as likely as those with adult-onset SLE to complete college education, childhood-onset SLE significantly increases the risk of not working in adulthood, even when controlling for disease and demographic factors. Exploring reasons for low rates of employment and providing vocational support may be important to maximize long-term functional outcomes in patients with childhood-onset SLE.

Vitrectomy for epiretinal membrane in adult-onset Coats' disease.

PubMed

Kumar, Pradeep; Kumar, Vinod

2017-10-01

Coats' disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats' disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats' disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed.

Movement and Other Neurodegenerative Syndromes in Patients with Systemic Rheumatic Diseases

PubMed Central

Menezes, Rikitha; Pantelyat, Alexander; Izbudak, Izlem; Birnbaum, Julius

2015-01-01

Abstract Patients with rheumatic diseases can present with movement and other neurodegenerative disorders. It may be underappreciated that movement and other neurodegenerative disorders can encompass a wide variety of disease entities. Such disorders are strikingly heterogeneous and lead to a wider spectrum of clinical injury than seen in Parkinson's disease. Therefore, we sought to stringently phenotype movement and other neurodegenerative disorders presenting in a case series of rheumatic disease patients. We integrated our findings with a review of the literature to understand mechanisms which may account for such a ubiquitous pattern of clinical injury. Seven rheumatic disease patients (5 Sjögren's syndrome patients, 2 undifferentiated connective tissue disease patients) were referred and could be misdiagnosed as having Parkinson's disease. However, all of these patients were ultimately diagnosed as having other movement or neurodegenerative disorders. Findings inconsistent with and more expansive than Parkinson's disease included cerebellar degeneration, dystonia with an alien-limb phenomenon, and nonfluent aphasias. A notable finding was that individual patients could be affected by cooccurring movement and other neurodegenerative disorders, each of which could be exceptionally rare (ie, prevalence of ∼1:1000), and therefore with the collective probability that such disorders were merely coincidental and causally unrelated being as low as ∼1-per-billion. Whereas our review of the literature revealed that ubiquitous patterns of clinical injury were frequently associated with magnetic resonance imaging (MRI) findings suggestive of a widespread vasculopathy, our patients did not have such neuroimaging findings. Instead, our patients could have syndromes which phenotypically resembled paraneoplastic and other inflammatory disorders which are known to be associated with antineuronal antibodies. We similarly identified immune-mediated and inflammatory markers

Anxiety disorders and drug dependence: evidence on sequence and specificity among adults.

PubMed

Goodwin, Renee D; Stein, Dan J

2013-04-01

The goal of this study was to investigate the relation between specific anxiety disorders and substance dependence, adjusting for potentially confounding demographic factors (e.g. sex) and comorbidity (e.g. alcohol dependence, major depression), among adults in the USA. Data were drawn from the National Comorbidity Survey (NCS), a nationally representative population sample of the US adult population aged 15-54. The temporal sequence of onset of anxiety and substance dependence disorders was examined. Substance dependence temporally precedes several anxiety disorders, particularly panic disorder. Specifically, a history of past substance dependence predicts current panic disorder (odds ratio [OR] =2.62, 95% confidence interval [CI] =1.29, 5.32), social phobia (OR=1.7, 95%CI=1.12, 2.41), and agoraphobia (OR=1.78, 95%CI=1.08, 2.94). Conversely, in more than 50% of substance abuse disorder cases, in nearly 40% of post-traumatic stress disorder (PTSD) cases, and in nearly 30% of generalized anxiety disorder (GAD) cases, the anxiety disorder has first onset. Similarly, a lifetime history of social phobia, PTSD, or GAD significantly predicts lifetime substance dependence (OR=1.51 for social phobia, 2.06 for PTSD, 1.45 for GAD). For any particular anxiety disorder, a diagnosis of substance abuse can occur prior to or subsequent to an anxiety disorder. Nevertheless, there is also evidence for the specificity of some associations between anxiety and substance dependence disorders; these are independent of the effects of sex and other comorbid disorders, may be causal in nature, and deserve particular attention in clinical settings. The possibility that within a particular anxiety disorder there are a variety of mechanisms of association with various substances should be addressed in future work. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Late-onset obsessive compulsive disorder associated with possible gliomatosis cerebri.

PubMed

Kumar, Vineet; Chakrabarti, Subho; Modi, Manish; Sahoo, Manoj

2009-01-01

Onset of obsessive-compulsive disorder (OCD) after the age of 50 years is rare, and should alert the physician to possible "organic" causes of OCD. These include infections, degenerative disorders, brain injury and cerebrovascular lesions, principally involving the frontal lobes and basal ganglia. The current patient had obsessive images, anxiety, auditory hallucinations and seizures following (possible) gliomatosis cerebri, with onset around 69 years of age. The atypical presentation, lesions involving the cortical-basal ganglia-thalamic-cortical circuit and the association with neurological signs/symptoms, was characteristic. However, late-onset OCD has not been commonly reported with diffuse lesions, and the association with gliomatosis cerebri is not known. This patient's case illustrates the need for careful screening of older patients with recently acquired OCD, and for further systematic study of OCD in the broad range of neuropsychiatric disorders affecting the elderly.

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

PubMed Central

Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X.-Q.; Beitel, Lenore K.; Durcan, Thomas M.

2018-01-01

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders. PMID:29467610

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.

PubMed

Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X-Q; Beitel, Lenore K; Durcan, Thomas M

2018-01-01

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop "first-of-their-kind" disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an "Open Science" model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

Niemann-Pick Disease Type C Presenting as a Developmental Coordination Disorder with Bullying by Peers in a School-Age Child

PubMed Central

Suzuki, Ryo; Tanaka, Atsushi; Matsui, Toshiharu; Gunji, Tetsuki; Tohyama, Jun; Nairita, Aya; Nanba, Eiji; Ohno, Kousaku

2015-01-01

Niemann-Pick disease type C (NPC) is a rare progressive neurodegenerative disorder, often with onset after normal early childhood development. Juvenile onset NPC patients slowly develop cerebellar symptoms and cognitive impairment and often experience difficulties at school. However, these problems may be overlooked due to the unpublicized nature of NPC, given that it is a rare metabolic disorder. In this report, we present an 11-year-old male NPC patient, who suffered from clumsiness and difficulties in attention and academic and social skills. His symptoms were initially considered to be due to developmental coordination disorder (DCD) coexisting with bullying by peers. DCD is a type of neurodevelopmental disorder defined according to DSM-IV and is characterized by clumsiness that interferes with academic achievement and social integration not due to other general medical conditions. However, a detailed investigation of the patient suggested that the problems could be attributed to the onset of NPC. Clinicians should keep neurodegenerative disorders as differential diagnosis of children with multiple school problems. PMID:26788393

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

PubMed

Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

2017-08-31

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

Attention-deficit hyperactivity disorder and anxiety disorders as precursors of bipolar disorder onset in adulthood.

PubMed

Meier, Sandra M; Pavlova, Barbara; Dalsgaard, Søren; Nordentoft, Merete; Mors, Ole; Mortensen, Preben B; Uher, Rudolf

2018-06-21

Attention-deficit hyperactivity disorder (ADHD) and anxiety disorders have been proposed as precursors of bipolar disorder, but their joint and relative roles in the development of bipolar disorder are unknown.AimsTo test the prospective relationship of ADHD and anxiety with onset of bipolar disorder. We examined the relationship between ADHD, anxiety disorders and bipolar disorder in a birth cohort of 2 409 236 individuals born in Denmark between 1955 and 1991. Individuals were followed from their sixteenth birthday or from January 1995 to their first clinical contact for bipolar disorder or until December 2012. We calculated incidence rates per 10 000 person-years and tested the effects of prior diagnoses on the risk of bipolar disorder in survival models. Over 37 394 865 person-years follow-up, 9250 onsets of bipolar disorder occurred. The incidence rate of bipolar disorder was 2.17 (95% CI 2.12-2.19) in individuals with no prior diagnosis of ADHD or anxiety, 23.86 (95% CI 19.98-27.75) in individuals with a prior diagnosis of ADHD only, 26.05 (95% CI 24.47-27.62) in individuals with a prior diagnosis of anxiety only and 66.16 (95% CI 44.83-87.47) in those with prior diagnoses of both ADHD and anxiety. The combination of ADHD and anxiety increased the risk of bipolar disorder 30-fold (95% CI 21.66-41.40) compared with those with no prior ADHD or anxiety. Early manifestations of both internalising and externalising psychopathology indicate liability to bipolar disorder. The combination of ADHD and anxiety is associated with a very high risk of bipolar disorder.Declaration of interestNone.

Does age at onset of first major depressive episode indicate the subtype of major depressive disorder?: the clinical research center for depression study.

PubMed

Park, Seon-Cheol; Hahn, Sang-Woo; Hwang, Tae-Yeon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

2014-11-01

The purpose of this study was to evaluate the effects of age at onset of the first major depressive episode on the clinical features of individuals with major depressive disorder (MDD) in a large cohort of Korean depressed patients. We recruited 419 MDD patients of age over 18 years from the Clinical Research Center for Depression study in South Korea. At the start of the study, the onset age of the first major depressive episode was self-reported by the subjects. The subjects were divided into four age-at-onset subgroups: childhood and adolescent onset (ages <18), early adult onset (ages 18-44), middle adult onset (ages 45-59), and late onset (ages 60+). Using analysis of covariance (ANCOVA) and ordinal logistic regression analysis with adjusting the effect of age, the relationships between clinical features and age at onset of MDD were evaluated. There was an apparent, but inconsistent correlation between clinical features and age at onset. Earlier onset MDD was significantly associated with higher proportion of female gender [adjusted odds ratio (AOR)=0.570, p=0.022], more previous suicide attempts (AOR=0.635, p=0.038), greater number of previous depressive episodes (F=3.475, p=0.016) and higher scores on the brief psychiatric rating scale (F=3.254, p=0.022), its negative symptom subscale (F=6.082, p<0.0001), and the alcohol use disorder identification test (F=7.061, p<0.0001). Early age at onset may increase the likelihood of distinguishable MDD subtype, and age at onset of the first major depressive episode is a promising clinical indicator for the clinical presentation, course, and outcome of MDD.

Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

PubMed

Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

2015-11-23

Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

Amyloid PET in neurodegenerative diseases with dementia.

PubMed

Camacho, V; Gómez-Grande, A; Sopena, P; García-Solís, D; Gómez Río, M; Lorenzo, C; Rubí, S; Arbizu, J

2018-05-15

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ 1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aβ amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

Aging Microglia—Phenotypes, Functions and Implications for Age-Related Neurodegenerative Diseases

PubMed Central

Spittau, Björn

2017-01-01

Aging of the central nervous system (CNS) is one of the major risk factors for the development of neurodegenerative pathologies such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). The molecular mechanisms underlying the onset of AD and especially PD are not well understood. However, neuroinflammatory responses mediated by microglia as the resident immune cells of the CNS have been reported for both diseases. The unique nature and developmental origin of microglia causing microglial self-renewal and telomere shortening led to the hypothesis that these CNS-specific innate immune cells become senescent. Age-dependent and senescence-driven impairments of microglia functions and responses have been suggested to play essential roles during onset and progression of neurodegenerative diseases. This review article summarizes the current knowledge of microglia phenotypes and functions in the aging CNS and further discusses the implications of these age-dependent microglia changes for the development and progression of AD and PD as the most common neurodegenerative diseases. PMID:28659790

Prevalence of comorbid substance use disorder during long-term central stimulant treatment in adult ADHD.

PubMed

Torgersen, Terje; Gjervan, Bjørn; Rasmussen, Kirsten; Vaaler, Arne; Nordahl, Hans M

2013-03-01

Central stimulant (CS) therapy is a cornerstone in treatment of adult attention-deficit/hyperactivity disorder (ADHD). Substance use disorder (SUD) is a common comorbid disorder of ADHD and might complicate the treatment. Our main objectives were to investigate the prevalence of SUD during CS treatment, and identify variables associated with SUD during the treatment. The collection of data was based on a naturalistic, retrospective approach using the medical records of a cohort of all adult ADHD patients (N = 117) starting treatment with CS in a specific catchment area in the period 1997 to May 2005. A logistic regression model was applied to identify possible predictors of SUD during CS treatment. The study showed no onset of SUD during the CS treatment in the group of patients without comorbid SUD at baseline (mean CS treatment length 41.1 months). In the group of patients with comorbid SUD at baseline, 58.5 % had one or more relapses of SUD during treatment (mean CS treatment length 27.9 months). Younger age and comorbid antisocial personality disorder were associated with relapse. In a logistic regression analysis, cannabis abstinence for more than 12 months was a negative predictor for relapse of SUD. CS treatment does not precipitate onset of SUD in adults without previous SUD.

Adult onset Hallervorden-Spatz disease with psychotic symptoms.

PubMed

del Valle-López, Pilar; Pérez-García, Rosa; Sanguino-Andrés, Rosa; González-Pablos, Emilio

2011-01-01

Hallervorden-Spatz disease is a rare neurological disorder characterized by pyramidal and extrapyramidal manifestations, dysarthria and dementia. Its onset is usually in childhood and most patients have a fatal outcome in few years. A high percentage of cases are hereditary with a recessive autosomal pattern. In the majority of the patients reported, a mutation of the gene that encodes the pantothenate kinase (PANK2) located in the 20p13-p12.3 chromosome that causes iron storage in the basal ganglia of the brain has been found. Its diagnosis is based on clinical symptoms as well as specific MRI imaging findings. The most common psychiatric features are cognitive impairment as well as depressive symptoms. There are few documented cases with psychotic disorders. We present the case of a patient with late onset Hallervorden-Spatz disease and psychotic symptoms that preceded the development of neurological manifestations. The pathophysiology and the treatment of psychotic symptomatology are presented and discussed. Key words: Psicosis, Hallervorden-Spatz, late onset, Basal ganglia.

Curcumin and neurodegenerative diseases

PubMed Central

Monroy, Adriana; Lithgow, Gordon J.; Alavez, Silvestre

2013-01-01

Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases. PMID:23303664

Age at Onset of Bipolar Disorder Related to Parental and Grandparental Illness Burden.

PubMed

Post, Robert M; Altshuler, Lori L; Kupka, Ralph; McElroy, Susan L; Frye, Mark A; Rowe, Michael; Grunze, Heinz; Suppes, Trisha; Keck, Paul E; Leverich, Gabriele S; Nolen, Willem A

2016-10-01

The age at onset of bipolar disorder varies greatly in different countries and continents. The association between load of family history of psychiatric illness and age at onset has not been adequately explored. 979 outpatients with bipolar disorder (from 4 sites in the United States and 3 in the Netherlands and Germany) gave informed consent and completed a questionnaire about their demographics, age at onset of illness, and family history of unipolar and bipolar disorder, alcohol and substance abuse comorbidity, suicide attempts, and "other" illnesses in their parents, 4 grandparents, and any offspring. We examined how the parental and grandparental burden of these illnesses related to the age at onset of the patients' bipolar disorder. The burden of family psychiatric history was strongly related to an earlier age at onset of illness in both US and European patients (F₃,₉₀₆ = 35.42, P < .0001). However, compared to the Europeans, patients in the United States had both more family history of most difficulties and notably earlier age at onset. Earlier age at onset was associated with a greater illness burden in the patient's offspring (t₅₆₈ = 4.1, P < .0001). More parental and grandparental psychiatric illness was associated with an earlier age at onset of bipolar disorder, which is earlier in the United States compared with Europe and is strongly related to a poor long-term prognosis. This apparent polygenic contribution to early onset deserves further study and therapeutic attempts at ameliorating the transgenerational impact. © Copyright 2016 Physicians Postgraduate Press, Inc.

Caring for Others: Internet Video-Conferencing Group Intervention for Family Caregivers of Older Adults with Neurodegenerative Disease

ERIC Educational Resources Information Center

Marziali, Elsa; Donahue, Peter

2006-01-01

Purpose: The aim of this pilot feasibility study was to evaluate the effects of an innovative, Internet-based psychosocial intervention for family caregivers of older adults with neurodegenerative disease. Design and Methods: After receiving signed informed consent from each participant, we randomly assigned 66 caregivers to an Internet-based…

Solar insolation in springtime influences age of onset of bipolar I disorder.

PubMed

Bauer, M; Glenn, T; Alda, M; Aleksandrovich, M A; Andreassen, O A; Angelopoulos, E; Ardau, R; Ayhan, Y; Baethge, C; Bharathram, S R; Bauer, R; Baune, B T; Becerra-Palars, C; Bellivier, F; Belmaker, R H; Berk, M; Bersudsky, Y; Bicakci, Ş; Birabwa-Oketcho, H; Bjella, T D; Bossini, L; Cabrera, J; Cheung, E Y W; Del Zompo, M; Dodd, S; Donix, M; Etain, B; Fagiolini, A; Fountoulakis, K N; Frye, M A; Gonzalez-Pinto, A; Gottlieb, J F; Grof, P; Harima, H; Henry, C; Isometsä, E T; Janno, S; Kapczinski, F; Kardell, M; Khaldi, S; Kliwicki, S; König, B; Kot, T L; Krogh, R; Kunz, M; Lafer, B; Landén, M; Larsen, E R; Lewitzka, U; Licht, R W; Lopez-Jaramillo, C; MacQueen, G; Manchia, M; Marsh, W; Martinez-Cengotitabengoa, M; Melle, I; Meza-Urzúa, F; Yee Ming, M; Monteith, S; Morken, G; Mosca, E; Munoz, R; Mythri, S V; Nacef, F; Nadella, R K; Nery, F G; Nielsen, R E; O'Donovan, C; Omrani, A; Osher, Y; Østermark Sørensen, H; Ouali, U; Pica Ruiz, Y; Pilhatsch, M; Pinna, M; da Ponte, F D R; Quiroz, D; Ramesar, R; Rasgon, N; Reddy, M S; Reif, A; Ritter, P; Rybakowski, J K; Sagduyu, K; Scippa, Â M; Severus, E; Simhandl, C; Stein, D J; Strejilevich, S; Subramaniam, M; Sulaiman, A H; Suominen, K; Tagata, H; Tatebayashi, Y; Tondo, L; Torrent, C; Vaaler, A E; Veeh, J; Vieta, E; Viswanath, B; Yoldi-Negrete, M; Zetin, M; Zgueb, Y; Whybrow, P C

2017-12-01

To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Management of neurodegenerative disorders: Parkinson's disease and Alzheimer's disease.

PubMed

Pal, P K; Netravathi, M

2005-03-01

Neurodegenerative disorders result from premature progressive degeneration of specific neurons, and manifest as diseases or syndromes with varied combinations of cognitive, motor, sensory and autonomic dysfunctions. The management involves pharmacotherapy as well as non-pharmacological measures and also to lessen the burden of the care-givers. The medications available for medical treatment are: Levodopa, dopamine agonists, amantadine, anticholinergics, enzyme inhibitors, etc. Advanced Parkinson's disease is concerned with management of motor complications and non-motor complications. Recently surgical treatment is a great option for managing motor complication. Orthostatic hypotension, gait distiurbances, emotional and psychiatric problems, sleep disturbances can be managed and had been discussed in brief. Currently there is no medication available for the cure of Alzheimer's disease. The specific medications claimed to improve patient's well being and cognition include cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonist, anti-oxidants, and anti-amyloid therapy. While medical and surgical treatments for Parkinson's disease have revolutionised the management, still drug therapy for Alzheimer's disease is dismal.

Vitrectomy for epiretinal membrane in adult-onset Coats’ disease

PubMed Central

Kumar, Pradeep; Kumar, Vinod

2017-01-01

Coats’ disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats’ disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats’ disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed. PMID:29044085

Age of onset of bipolar disorder: Combined effect of childhood adversity and familial loading of psychiatric disorders.

PubMed

Post, Robert M; Altshuler, Lori L; Kupka, Ralph; McElroy, Susan L; Frye, Mark A; Rowe, Michael; Grunze, Heinz; Suppes, Trisha; Keck, Paul E; Leverich, Gabriele S; Nolen, Willem A

2016-10-01

Family history and adversity in childhood are two replicated risk factors for early onset bipolar disorder. However, their combined impact has not been adequately studied. Based on questionnaire data from 968 outpatients with bipolar disorder who gave informed consent, the relationship and interaction of: 1) parental and grandparental total burden of psychiatric illness; and 2) the degree of adversity the patient experienced in childhood on their age of onset of bipolar disorder was examined with multiple regression and illustrated with a heat map. The familial loading and child adversity vulnerability factors were significantly related to age of onset of bipolar and their combined effect was even larger. A heat map showed that at the extremes (none of each factor vs high amounts of both) the average age of onset differed by almost 20 years (mean = 25.8 vs 5.9 years of age). The data were not based on interviews of family members and came from unverified answers on a patient questionnaire. Family loading for psychiatric illness and adversity in childhood combine to have a very large influence on age of onset of bipolar disorder. These variables should be considered in assessment of risk for illness onset in different populations, the need for early intervention, and in the design of studies of primary and secondary prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Epigenetic heredity (deoxyribonucleic acid methylation): Clinical context in neurodegenerative disorders and ATXN2 gene].

PubMed

Laffita-Mesa, José Miguel; Bauer, Peter

2014-10-21

Epigenetics is the group of changes in the phenotype which are related with the process independently of the primary DNA sequence. These changes are intimately related with changes in the gene expression level and its profile across the body. These are mediated by histone tail modifications, DNA methylation, micro-RNAs, with chromatin remodeling remaining as the foundation of epigenetic changes. DNA methylation involves the covalent addition of methyl group to cytosine of the DNA, which is mediated by methyltransferases enzymes. DNA methylation regulates gene expression by repressing transcription, while de-methylation activates gene transcription. Several human diseases are related with the epigenetic process: cancer, Alzheimer disease, stroke, Parkinson disease, and diabetes. We present here the basis of epigenetic inheritance and show the pathogenic mechanisms relating epigenetics in human diseases, specifically with regard to neurodegeneration. We discuss current concepts aimed at understanding the contribution of epigenetics to human neurodegenerative diseases. We also discuss recent findings obtained in our and other centers regarding the ATXN2 gene that causes spinocerebellar ataxia 2 and amyotrophic lateral sclerosis. Epigenetics play a pivotal role in the pathogenesis of human diseases and in several neurodegenerative disorders, and this knowledge will illuminate the pathways in the diagnostic and therapeutic field, which ultimately will be translated into the clinic context of neurodegenerative diseases. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Age of onset of mental disorders: A review of recent literature

PubMed Central

Kessler, Ronald C.; Amminger, G. Paul; Aguilar‐Gaxiola, Sergio; Alonso, Jordi; Lee, Sing; Ustun, T. Bedirhan

2007-01-01

Purpose of the review To review recent epidemiological research on age‐of‐onset (AOO) of mental disorders, focusing on the WHO World Mental Health (WMH) surveys. Recent findings Median and inter‐quartile range (IQR; 25th–75th percentiles) of AOO is much earlier for phobias (7–14, IQR: 4–20) and impulse‐control disorders (7–15, IQR: 4–35) than other anxiety disorders (25–53, IQR: 15–75), mood disorders (25–45, IQR: 17–65), and substance disorders (18–29, IQR: 16–43). Although less data exist for non‐affective psychosis, available evidence suggests that median AOO is in the range late teens through early 20s. Roughly half of all lifetime mental disorders in most studies start by the mid‐teens and three‐fourths by the mid‐20s. Later onsets are mostly secondary conditions. Severe disorders are typically preceded by less severe disorders that seldom are brought to clinical attention. Summary First onset of mental disorders usually occurs in childhood or adolescence, although treatment typically does not occur until a number of years later. Although interventions with early incipient disorders might help reduce severity‐persistence of primary disorders and prevent secondary disorders, additional research is needed on appropriate treatments for early incipient cases and on long‐term evaluation of the effects of early intervention on secondary prevention. PMID:17551351

Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy.

PubMed

Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

2016-12-27

Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD.

Differences in disease features between childhood-onset and adult-onset systemic lupus erythematosus patients presenting with acute abdominal pain.

PubMed

Tu, Yu-Ling; Yeh, Kuo-Wei; Chen, Li-Chen; Yao, Tsung-Chieh; Ou, Liang-Shiou; Lee, Wen-I; Huang, Jing-Long

2011-04-01

Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain. A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain. The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P < 0.001) at the time of admission. The overall case fatality rate of acute abdomen in SLE patients was 9.4%. The extra-gastrointestinal symptoms, laboratory evaluation, disease activity, and organ damage measured by the SLE Disease Activity Index and outcomes were comparable between children and adults. Various etiologies of acute abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Obesity's Effects on the Onset of Functional Impairment among Older Adults

ERIC Educational Resources Information Center

Jenkins, Kristi Rahrig

2004-01-01

Purpose: This study has two purposes. First, it determines if there is a relationship between body weight and the onset of functional impairment across time among this sample of older adults. More specifically, it examines if obese older adults are more likely to experience the onset of functional impairment. Second, it explores how health…

Annual Research Review: Transgenic Mouse Models of Childhood-Onset Psychiatric Disorders

ERIC Educational Resources Information Center

Robertson, Holly R.; Feng, Guoping

2011-01-01

Childhood-onset psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), mood disorders, obsessive compulsive spectrum disorders (OCSD), and schizophrenia (SZ), affect many school-age children, leading to a lower quality of life, including difficulties in school and personal relationships that…

29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype.

PubMed

Monin, Marie-Lorraine; Mignot, Cyril; De Lonlay, Pascale; Héron, Bénédicte; Masurel, Alice; Mathieu-Dramard, Michèle; Lenaerts, Catherine; Thauvin, Christel; Gérard, Marion; Roze, Emmanuel; Jacquette, Aurélia; Charles, Perrine; de Baracé, Claire; Drouin-Garraud, Valérie; Khau Van Kien, Philippe; Cormier-Daire, Valérie; Mayer, Michèle; Ogier, Hélène; Brice, Alexis; Seta, Nathalie; Héron, Delphine

2014-12-11

PMM2-CDG (formerly known as CDG Ia) a deficiency in phosphomannomutase, is the most frequent congenital disorder of glycosylation. The phenotype encompasses a wide range of neurological and non-neurological manifestations comprising cerebellar atrophy and intellectual deficiency. The phenotype of the disorder is well characterized in children but the long term course of the disease is unknown and the phenotype of late onset forms has not been comprehensively described. We thus retrospectively collected the clinical, biological and radiological data of 29 French PMM2-CDG patients aged 15 years or more with a proven molecular diagnosis (16 females and 13 males). In addition, thirteen of these patients were reexamined at the time of the study to obtain detailed information. 27 of the 29 patients had a typical PMM2-CDG phenotype, with infantile hypotonia, strabismus, developmental delay followed by intellectual deficiency, epilepsy, retinitis pigmentosa and/or visceral manifestations. The main health problems for these patients as teenagers and in adulthood were primary ovarian insufficiency, growth retardation, coagulation anomalies and thrombotic events, skeletal deformities and osteopenia/osteoporosis, retinitis pigmentosa, as well as peripheral neuropathy. Three patients had never walked and three lost their ability to walk. The two remaining patients had a late-onset phenotype unreported to date. All patients (n = 29) had stable cerebellar atrophy. Our findings are in line with those of previous adult PMM2-CDG cohorts and points to the need for a multidisciplinary approach to the follow up of PMM2-CDG patients to prevent late complications. Additionally, our findings add weight to the view that PMM2-CDG may be diagnosed in teenage/adult patients with cerebellar atrophy, even in the absence of intellectual deficiency or non-neurological involvement.

Anti-inflammatory effects of flavonoids in neurodegenerative disorders.

PubMed

Spagnuolo, Carmela; Moccia, Stefania; Russo, Gian Luigi

2018-06-10

Neuroinflammation is one of the main mechanisms involved in the progression of several neurodegenerative diseases, such as Parkinson, Alzheimer, multiple sclerosis, amyotrophic lateral sclerosis and others. The activation of microglia is the main feature of neuroinflammation, promoting the release of pro-inflammatory cytokines and resulting in the progressive neuronal cell death. Natural compounds, such as flavonoids, possess neuroprotective potential probably related to their ability to modulate the inflammatory responses involved in neurodegenerative diseases. In fact, pure flavonoids (e.g., quercetin, genistein, hesperetin, epigallocatechin-3-gallate) or enriched-extracts, can reduce the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2), down-regulate inflammatory markers and prevent neural damage. This anti-inflammatory activity is primarily related to the regulation of microglial cells, mediated by their effects on MAPKs and NF-κB signalling pathways, as demonstrated by in vivo and in vitro data. The present work reviews the role of inflammation in neurodegenerative diseases, highlighting the potential therapeutic effects of flavonoids as a promising approach to develop innovative neuroprotective strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

Adult-Onset Offending: A Neglected Reality? Findings From a Contemporary British General Population Cohort.

PubMed

Sapouna, Maria

2017-09-01

There is disagreement in the literature as to whether there are any true adult-onset offenders. The aim of this study is to investigate the prevalence and correlates of adult-onset offenders in a contemporary British general population cohort consisting of 739 individuals aged between 18 and 25 years. Sixteen percent of participants reported offending for the first time after the age of 18. It is concluded that adult-onset exists and deserves to be studied further. Adult-onset offenders were more likely to report using drugs, associating with deviant peers, and having mental health problems in adulthood than non-offenders. Compared with early-onset offenders, the adult-onset offenders were people with a stronger attachment to school, which may have protected them from the risk of offending in adolescence. It is possible that when that protection was removed in adulthood and they were exposed to negative life events, such as drug use and mental illness, they became involved in crime for the first time.

Social, educational and vocational outcomes in patients with childhood-onset and young-adult-onset growth hormone deficiency.

PubMed

Mitra, M Tanya; Jönsson, Peter; Åkerblad, Ann-Charlotte; Clayton, Peter; Kołtowska-Häggström, Maria; Korbonits, Márta; Toogood, Andy; Gleeson, Helena

2017-04-01

Hypopituitarism diagnosed in childhood, adolescence and young adulthood has the potential to affect growth and somatic development. Less is known about the impact of such a diagnosis on other aspects of development. An analysis of the KIMS database (Pfizer International Metabolic Database) was performed to explore social, educational and vocational outcomes of adult patients diagnosed in childhood, adolescence and young adulthood compared with adult-onset controls. A total of 2952 adult patients diagnosed with hypothalamic pituitary conditions before the age of 25 were divided into two groups: childhood-onset [<16 years (CO)] (n = 1782) and young-adult-onset [16 to <25 years (YAO)] (n = 1170). A total of 1617 adult patients diagnosed with a nonfunctioning pituitary adenoma at the age of 25 or older formed the adult-onset control group (AO). KIMS Patient Life Situation Form which provided information on social, educational and vocational outcomes. Compared with the AO control group, CO and YAO patients were between 4·5 and 8·0 times more likely to live with their parents in adulthood; CO and YAO patients were also less likely to live in partnership and to have children. The impact on educational and vocational outcomes was less marked than on social outcomes with no significant differences compared with the AO control group. Educational and vocational outcomes showed the lowest level in male and female CO and YAO patients who had been previously diagnosed with a brain tumour. Social outcomes were more affected than educational and vocational outcomes. Although CO patients are more adversely affected, YAO patients were also failing to achieve social milestones. This has consequences for the delivery of endocrine care in both paediatric and adult services. © 2016 John Wiley & Sons Ltd.

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

PubMed

Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

2015-01-01

After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

PubMed Central

Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

2015-01-01

Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

Autophagy of Mitochondria: A Promising Therapeutic Target for Neurodegenerative Disease

PubMed Central

Kamat, Pradip K.; Kalani, Anuradha; Kyles, Philip; Tyagi, Suresh C.; Tyagi, Neetu

2014-01-01

The autophagic process is the only known mechanism for mitochondrial turnover and it has been speculated that dysfunction of autophagy may result in mitochondrial error and cellular stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is associated with cellular oxidative stress and its impact on neuro-degeneration. This impaired autophagic function may be considered as a possible mechanism in the pathogenesis of several neurodegenerative disorders including: Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington disease (HD). It can be suggested that autophagy dysfunction along with oxidative stress are considered main events in neurodegenerative disorders. New therapeutic approaches have now begun to target mitochondria as a potential drug target. This review discusses evidence supporting the notion that oxidative stress and autophagy are intimately associated with neurodegenerative disease pathogenesis. This review also explores new approaches that can prevent mitochondrial dysfunction, improve neurodegenerative etiology, and also offer possible cures to the aforementioned neurodegenerative diseases. PMID:24807843

Early childhood sleep and eating problems as predictors of adolescent and adult mood and anxiety disorders.

PubMed

Ong, Say How; Wickramaratne, Priya; Tang, Min; Weissman, Myrna M

2006-11-01

Recent studies have suggested that eating and sleep problems during early childhood may pose as risk factors for mood and anxiety disorders in later life. We aim to study the associations between early childhood sleep and eating problems, specifically high motor activity during sleep and irregularities in sleep/eating schedules, and lifetime history of mood and anxiety disorders. We followed up 164 offspring, who were at high and low risk for major depression by virtue of their parental history (at least one parent had Major Depressive Disorder). Target sleep and eating problems were measured using Dimensions of Temperament Survey (DOTS). The offspring were blindly assessed at 3 times over 20 years using a structured diagnostic interview. Irregularities in sleeping and eating schedules in childhood (low rhythmicity) was associated with adolescent-onset major depression and anxiety disorder, as well as childhood-onset anxiety disorder. High motor activity level during sleep was associated with both childhood-onset and adolescent-onset dysthymic disorder. Neither childhood sleep nor eating irregularities were associated with adult onset psychopathology. Retrospective reports of childhood sleep and eating patterns were derived from parent-reports. Reported problems may overlap with clinical diagnoses. Clinicians should be alerted to parental reports of children's sleep and eating problems suggesting low rhythmicity, as well as high motor activity levels during sleep. These early behaviors may be predictive of subsequent mood and anxiety disorders in childhood and adolescence.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

PubMed

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

The distinction between juvenile and adult-onset primary open-angle glaucoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiggs, J.L.; Haines, J.L.; Damji, K.F.

1996-01-01

Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light ofmore » the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.« less

Psychological treatment of attention deficit hyperactivity disorder in adults: a systematic review.

PubMed

Vidal-Estrada, Raquel; Bosch-Munso, Rosa; Nogueira-Morais, Mariana; Casas-Brugue, Miquel; Ramos-Quiroga, Josep A

2012-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder of childhood onset. The disorder persists into adulthood in most cases, significantly affecting patient function. Although the firstline choice of treatment for ADHD is pharmacological, drug treatments are not always sufficient. All the published studies on the psychological treatment of ADHD were systematically reviewed for the present article. The MEDLINE and PsychINFO electronic databases were searched using the terms psychological treatment OR psychotherapy OR psychosocial treatment AND ADHD. Patient age was restricted to adults (all adult:19+ years). Eighteen published studies met inclusion criteria for the review. Fifteen efficacy studies of psychological treatment were selected (cognitive behavioral therapy, metacognitive therapy, dialectical behavior therapy, coaching, cognitive remediation) and three previous reviews. The results indicate that cognitive behavioral therapy is the most effective psychological treatment for ADHD symptoms in adults and the comorbid symptoms of anxiety and depression, which have an important functional impact on the daily life of patients. However, more research is needed to know the differential effects of each psychological approach in relation to improved ADHD symptoms in adults. Finally, future directions for the psychosocial treatment of ADHD problems of adults are suggested.

Adult-Onset Asthma Becomes the Dominant Phenotype among Women by Age 40 Years. The Longitudinal CARDIA Study

PubMed Central

Qualls, Clifford; Schuyler, Mark; Arynchyn, Alexander; Alvarado, Jesse H.; Smith, Lewis J.; Jacobs, David R.

2013-01-01

Rationale: Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported. Objectives: To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset. Methods: This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort in the United States over a 25-year period. Adult- and pediatric-onset asthma phenotypes were studied, as defined by age at onset of 18 years or older. Subjects with asthma were categorized by sex, obesity, atopy, smoking, and race by mean age/examination year, using a three-way analysis of covariance model. Natural history of disease was examined using probabilities derived from a Markov chain model. Measurements and Main Results: Asthma of adult onset became the dominant (i.e., exceeded 50%) phenotype in women by age 40 years. The age by which adult-onset asthma became the dominant phenotype was further lowered for obese, nonatopic, ever-smoking, or white women. The prevalence trend with increasing time for adult-onset disease was greater among subjects with nonatopic than atopic asthma among both sexes. Furthermore, adult-onset asthma had remarkable sex-related differences in risk factors. In both sexes, the quiescent state for adult-onset asthma was less frequent and also “less stable” over time than for pediatric-onset asthma. Conclusions: Using a large national cohort, this study challenges the dictum that most asthma in adults originates in childhood. Studies of the differences between pediatric- and adult-onset asthma may provide greater insight into the phenotypic heterogeneity of asthma. PMID:23802814

Personality Disorder Symptom Severity Predicts Onset of Mood Episodes and Conversion to Bipolar I Disorder in Individuals with Bipolar Spectrum Disorder

PubMed Central

Ng, Tommy H.; Burke, Taylor A.; Stange, Jonathan P.; Walshaw, Patricia D.; Weiss, Rachel B.; Urosevic, Snezana; Abramson, Lyn Y.; Alloy, Lauren B.

2017-01-01

Although personality disorders (PDs) are highly comorbid with bipolar spectrum disorders (BSDs), little longitudinal research has been conducted to examine the prospective impact of PD symptoms on the course of BSDs. The aim of this study is to examine whether PD symptom severity predicts shorter time to onset of bipolar mood episodes and conversion to bipolar I disorder over time among individuals with less severe BSDs. Participants (n = 166) with bipolar II disorder, cyclothymia, or bipolar disorder not otherwise specified completed diagnostic interview assessments of PD symptoms and self-report measures of mood symptoms at baseline. They were followed prospectively with diagnostic interviews every four months for an average of 3.02 years. Cox proportional hazard regression analyses indicated that overall PD symptom severity significantly predicted shorter time to onset of hypomanic (hazard ratio [HR]= 1.42; p < .001) and major depressive episodes (HR = 1.51; p < .001) and conversion to bipolar I disorder (HR = 2.51; p < .001), after controlling for mood symptoms. Results also suggested that cluster B severity predicted shorter time to onset of hypomanic episodes (HR = 1.38; p = .002) and major depressive episodes (HR = 1.35; p = .01) and conversion to bipolar I disorder (HR = 2.77; p < .001), whereas cluster C severity (HR= 1.56; p < .001) predicted shorter time to onset of major depressive episodes. These results support predisposition models in suggesting that PD symptoms may act as a risk factor for a more severe course of BSDs. PMID:28368159

Multiple roles of HDAC inhibition in neurodegenerative conditions

PubMed Central

Chuang, De-Maw; Leng, Yan; Marinova, Zoya; Kim, Hyeon-Ju; Chiu, Chi-Tso

2009-01-01

Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. Imbalances in protein acetylation levels and dysfunctions in transcription are associated with a wide variety of brain disorders. Treatment with various HDAC inhibitors corrects these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative diseases. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties, and improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in treating neurodegenerative disorders. PMID:19775759

Comparisons of intellectual capacities between mild and classic adult-onset phenotypes of myotonic dystrophy type 1 (DM1).

PubMed

Jean, Stéphane; Richer, Louis; Laberge, Luc; Mathieu, Jean

2014-11-26

Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic multisystem disorder and the commonest adult-onset form of muscular dystrophy. DM1 results from the expansion of an unstable trinucleotide cytosine-thymine-guanine (CTG) repeat mutation. CTG repeats in DM1 patients can range from 50 to several thousands, with a tendency toward increased repeats with successive generations (anticipation). Associated findings can include involvements in almost every systems, including the brain, and cognitive abnormalities occur in the large majority of patients. The objectives are to describe and compare the intellectual abilities of a large sample of DM1 patients with mild and classic adult-onset phenotypes, to estimate the validity of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in DM1 patients with muscular weakness, and to appraise the relationship of intelligence quotient (IQ) to CTG repeat length, age at onset of symptoms, and disease duration. A seven-subtest WAIS-R was administered to 37 mild and 151 classic adult-onset DM1 patients to measure their Full-Scale (FSIQ), Verbal (VIQ) and Performance IQ (PIQ). To control for potential bias due to muscular weakness, Standard Progressive Matrices (SPM), a motor-independent test of intelligence, were also completed. Total mean FSIQ was 82.6 corresponding to low average IQ, and 82% were below an average intelligence. Mild DM1 patients had a higher mean FSIQ (U=88.7 vs 81.1, p<0.001), VIQ (U=87.8 vs 82.3, p=0.001), and PIQ (U=94.8 vs 83.6, p<0.001) than classic adult-onset DM1 patients. In both mild and classic adult-onset patients, all subtests mean scaled scores were below the normative sample mean. FSIQ also strongly correlate with SPM (r s =0.67, p<0.001), indicating that low intelligence scores are not a consequence of motor impairment. FSIQ scores decreased with both the increase of (CTG)n (r s =-0.41, p<0.001) and disease duration (r s =-0.26, p=0.003). Results show that intellectual impairment is an

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

PubMed

Washington, Patricia M; Villapol, Sonia; Burns, Mark P

2016-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should it be classified together as traumatic encephalopathy?

PubMed Central

Washington, Patricia M.; Villapol, Sonia; Burns, Mark P.

2015-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer’s disease (AD), while mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position—examining epidemiological and case-control human studies, neuropathological evidence, and preclinical studies. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson’s disease. Further, human post-mortem studies on either single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a ‘polypathology’. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI are viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. PMID:26091850

Rhythmic movement disorder (head banging) in an adult during rapid eye movement sleep.

PubMed

Anderson, Kirstie N; Smith, Ian E; Shneerson, John M

2006-06-01

Sleep-related rhythmic movements (head banging or body rocking) are extremely common in normal infants and young children, but less than 5% of children over the age of 5 years old exhibit these stereotyped motor behaviors. They characteristically occur during drowsiness or sleep onset rather than in deep sleep or rapid eye movement (REM) sleep. We present a 27-year-old man with typical rhythmic movement disorder that had persisted into adult life and was restricted to REM sleep. This man is the oldest subject with this presentation reported to date and highlights the importance of recognizing this nocturnal movement disorder when it does occur in adults.

Toxic Proteins in Neurodegenerative Disease

NASA Astrophysics Data System (ADS)

Taylor, J. Paul; Hardy, John; Fischbeck, Kenneth H.

2002-06-01

A broad range of neurodegenerative disorders is characterized by neuronal damage that may be caused by toxic, aggregation-prone proteins. As genes are identified for these disorders and cell culture and animal models are developed, it has become clear that a major effect of mutations in these genes is the abnormal processing and accumulation of misfolded protein in neuronal inclusions and plaques. Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders.

Key goals and indicators for successful aging of adults with early-onset disability.

PubMed

LaPlante, Mitchell P

2014-01-01

Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

The Onset of Depression During the Great Recession: Foreclosure and Older Adult Mental Health

PubMed Central

Cagney, Kathleen A.; Browning, Christopher R.; Iveniuk, James; English, Ned

2014-01-01

Objectives. We examined neighborhood-level foreclosure rates and their association with onset of depressive symptoms in older adults. Methods. We linked data from the National Social Life, Health, and Aging Project (2005–2006 and 2010–2011 waves), a longitudinal, nationally representative survey, to data on zip code–level foreclosure rates, and predicted the onset of depressive symptoms using logit-linked regression. Results. Multiple stages of the foreclosure process predicted the onset of depressive symptoms, with adjustment for demographic characteristics and changes in household assets, neighborhood poverty, and visible neighborhood disorder. A large increase in the number of notices of default (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.14, 2.67) and properties returning to ownership by the bank (OR = 1.62; 95% CI = 1.06, 2.47) were associated with depressive symptoms. A large increase in properties going to auction was suggestive of such an association (OR = 1.45; 95% CI = 0.96, 2.19). Age, fewer years of education, and functional limitations also were predictive. Conclusions. Increases in neighborhood-level foreclosure represent an important risk factor for depression in older adults. These results accord with previous studies suggesting that the effects of economic crises are typically first experienced through deficits in emotional well-being. PMID:24446830

Anorexia nervosa 6 years after onset: Part I. Personality disorders.

PubMed

Gillberg, I C; Råstam, M; Gillberg, C

1995-01-01

Fifty-one adolescent-onset anorexia nervosa (AN) cases recruited after community screening were compared with 51 age-, sex-, and school-matched cases with regard to personality disorders and autism-spectrum disorders (ASD)/empathy disorders at age 21 years. All 102 cases had originally been examined at a mean age of 16 years, slightly over a year after the reported onset of the eating disorder. Structured Clinical Interview for DSM-III-R (SCID) interviews were performed by a psychiatrist blind to the original eating disorder diagnosis. Most of the former AN cases were recovered with respect to weight, but the outcome in social areas was restricted. Personality disorders coded on axis II in the DSM-III-R and empathy disorders were much more common in the AN group than in the comparison (COMP) group. Obsessive-compulsive (OCD) and avoidant personality disorders were particularly common. Obsessive-compulsive behaviors showed a high degree of stability over time and were unrelated to weight problems. Together with empathy disorder, they tended to predict outcome better than the eating disorder as such. It is concluded that in some cases, AN may be seen to reflect but one axis I diagnosis occurring in the life of an individual with a chronic personality disorder.

Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

ERIC Educational Resources Information Center

de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

2007-01-01

This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

Internalizing and externalizing psychopathology as predictors of cannabis use disorder onset during adolescence and early adulthood.

PubMed

Farmer, Richard F; Seeley, John R; Kosty, Derek B; Gau, Jeff M; Duncan, Susan C; Lynskey, Michael T; Lewinsohn, Peter M

2015-09-01

Risk-related liabilities associated with the development of cannabis use disorders (CUDs) during adolescence and early adulthood are thought to be established well before the emergence of the index episode. In this study, internalizing and externalizing psychopathology from earlier developmental periods were evaluated as risk factors for CUDs during adolescence and early adulthood. Participants (N = 816) completed 4 diagnostic assessments between the ages 16 and 30, during which current and past CUDs were assessed as well as a full range of psychiatric disorders associated with internalizing and externalizing psychopathology domains. In unadjusted and adjusted time-to-event analyses, externalizing but not internalizing psychopathology from proximal developmental periods predicted subsequent CUD onset. A large proportion of adolescent and early adult cases, however, did not manifest any externalizing or internalizing psychopathology during developmental periods before CUD onset. Findings are consistent with the emerging view that externalizing disorders from proximal developmental periods are robust risk factors for CUDs. Although the identification of externalizing liabilities may aid in the identification of individuals at risk for embarking on developmental pathways that culminate in CUDs, such liabilities are an incomplete indication of overall risk. (c) 2015 APA, all rights reserved).

Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood.

PubMed

Wilson, S; Hicks, B M; Foster, K T; McGue, M; Iacono, W G

2015-02-01

Major depressive disorder (MDD) that onsets by adolescence is associated with various deficits in psychosocial functioning. However, adolescent-onset MDD often follows a recurrent course that may drive its associated impairment. To tease apart these two clinical features, we examined the relative associations of age of onset (adolescent versus adult) and course (recurrent versus single episodes) of MDD with a broad range of psychosocial functioning outcomes assessed in early adulthood. Participants comprised a large, population-based sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252) assessed prospectively from ages 17 to 29 years. A recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood. The negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

Sleep Patterns in Adults with a Diagnosis of High-Functioning Autism Spectrum Disorder

PubMed Central

Baker, Emma K.; Richdale, Amanda L.

2015-01-01

Study Objectives: To examine sleep patterns and sleep problems and their relationship with daytime functioning in adults with a diagnosis of an autism spectrum disorder and no comorbid intellectual disability (high-functioning autism spectrum disorder [HFASD]) compared to neurotypical (NT) adults. Design: Cross-sectional. Setting: Home-based study. Participants: 36 adults with HFASD and 36 age-, intelligence quotient- and sex-matched NT adults. Measurements: Participants completed an online questionnaire battery including the Pittsburgh Sleep Quality Index (PSQI), a 14-d sleep wake diary and 14-d actigraphy data collection. Results: Adults with HFASD had significantly more general sleep disturbances and higher scores on the PSQI, longer sleep onset latencies (actigraphy), and poorer sleep efficiency (diary) and these results remained significant after accounting for the False Discovery Rate. Those adults with HFASD who did not have a comorbid diagnosis of anxiety/depression had significantly shorter total sleep time (diary and actigraphy) compared to NT adults. Compared to NT adults, the HFASD group self-reported significantly poorer refreshment scores upon waking in the morning and higher scores on the daytime dysfunction due to sleepiness subscale of the PSQI. Conclusions: These findings support the notion that problems related to sleep, in particular insomnia, continue into adulthood in individuals with high-functioning autism spectrum disorder. Citation: Baker EK, Richdale AL. Sleep patterns in adults with a diagnosis of high-functioning autism spectrum disorder. SLEEP 2015;38(11):1765–1774. PMID:26237770

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

PubMed

Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

2016-01-01

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the

Personality disorder symptom severity predicts onset of mood episodes and conversion to bipolar I disorder in individuals with bipolar spectrum disorder.

PubMed

Ng, Tommy H; Burke, Taylor A; Stange, Jonathan P; Walshaw, Patricia D; Weiss, Rachel B; Urosevic, Snezana; Abramson, Lyn Y; Alloy, Lauren B

2017-04-01

Although personality disorders (PDs) are highly comorbid with bipolar spectrum disorders (BSDs), little longitudinal research has been conducted to examine the prospective impact of PD symptoms on the course of BSDs. The aim of this study is to examine whether PD symptom severity predicts shorter time to onset of bipolar mood episodes and conversion to bipolar I disorder over time among individuals with less severe BSDs. Participants (n = 166) with bipolar II disorder, cyclothymia, or bipolar disorder not otherwise specified completed diagnostic interview assessments of PD symptoms and self-report measures of mood symptoms at baseline. They were followed prospectively with diagnostic interviews every 4 months for an average of 3.02 years. Cox proportional hazard regression analyses indicated that overall PD symptom severity significantly predicted shorter time to onset of hypomanic (hazard ratio [HR] = 1.42; p < .001) and major depressive episodes (HR = 1.51; p < .001) and conversion to bipolar I disorder (HR = 2.51; p < .001), after controlling for mood symptoms. Results also suggested that cluster B severity predicted shorter time to onset of hypomanic episodes (HR = 1.38; p = .002) and major depressive episodes (HR = 1.35; p = .01) and conversion to bipolar I disorder (HR = 2.77; p < .001), whereas cluster C severity (HR = 1.56; p < .001) predicted shorter time to onset of major depressive episodes. These results support predisposition models in suggesting that PD symptoms may act as a risk factor for a more severe course of BSDs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Gambling disorder in older adults: a cross-cultural perspective.

PubMed

Medeiros, Gustavo Costa; Leppink, Eric; Yaemi, Ana; Mariani, Mirella; Tavares, Hermano; Grant, Jon

2015-04-01

Gambling disorder (GD) in older adults is significantly increasing and became an important public health issue in different countries. However, little is known regarding GD in older adults. The prevalence and acceptance of gambling vary among different cultures and this raises the question of how and to what extent culture affects older gamblers. The majority of the important studies regarding GD in older adults have been conducted mainly in Anglo-Saxon cultures and little information is available regarding GD in other cultures. The objective of this paper is to perform the first standardized cross-cultural comparison regarding older adults presenting GD. The total studied sample involved 170 subjects: 89 from the Brazilian (BR) sample and 81 from the American (US) sample. It consisted of 67 men and 103 women (average age=64.42, standard deviation=±3.86). They were evaluated for socio-demographics, gambling behavior variables and psychiatric antecedents. Overall, there were significant differences between BR and US older adult gamblers in marital status, onset of gambling activity, onset of GD and urge scores. This study showed that there are important differences in gambling course, gambling behavior and personal antecedents between two samples of older adults presenting GD from countries with different social-cultural background. It weakens the possibility of generalization of results found in Anglo-Saxon countries to other cultures and reinforces for the need for development of research on GD in older adults outside the Anglo-Saxon culture. Copyright © 2014 Elsevier Inc. All rights reserved.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Behavioral Phenotyping Assays for Genetic Mouse Models of Neurodevelopmental, Neurodegenerative, and Psychiatric Disorders.

PubMed

Sukoff Rizzo, Stacey J; Crawley, Jacqueline N

2017-02-08

Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

ERIC Educational Resources Information Center

Danner, Stephanie; Fristad, Mary A.; Arnold, L. Eugene; Youngstrom, Eric A.; Birmaher, Boris; Horwitz, Sarah M.; Demeter, Christine; Findling, Robert L.; Kowatch, Robert A.

2009-01-01

Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

PubMed

Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

2013-06-01

The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

[Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort].

PubMed

Duarte, Angela P; Marques, Cláudia D L; Bortoluzzo, Adriana B; Gonçalves, Célio R; da Silva, José Antonio Braga; Ximenes, Antonio Carlos; Bértolo, Manoel B; Ribeiro, Sandra Lúcia E; Keiserman, Mauro; Skare, Thelma L; Carneiro, Sueli; Menin, Rita; Azevedo, Valderilio F; Vieira, Walber P; Albuquerque, Elisa N; Bianchi, Washington A; Bonfiglioli, Rubens; Campanholo, Cristiano; Carvalho, Hellen M S; Costa, Izaias P; Kohem, Charles L; Leite, Nocy; Lima, Sonia A L; Meirelles, Eduardo S; Pereira, Ivânio A; Pinheiro, Marcelo M; Polito, Elizandra; Resende, Gustavo G; Rocha, Francisco Airton C; Santiago, Mittermayer B; Sauma, Maria de Fátima L C; Valim, Valéria; Sampaio-Barros, Percival D; Barros, Percival D Sampaio

2014-01-01

To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Hemichannels in neurodegenerative diseases: is there a link to pathology?

PubMed Central

Bosch, Megan; Kielian, Tammy

2014-01-01

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario has been suggested for multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and more recently, lysosomal storage disorders, which are the focus of this perspective. Currently available evidence suggests a complex role for HCs in neurodegenerative disorders, which sets the stage for future studies to determine whether targeting HC action may improve disease outcomes. PMID:25191227

Adrenomedullin, a Novel Target for Neurodegenerative Diseases.

PubMed

Ferrero, Hilda; Larrayoz, Ignacio M; Gil-Bea, Francisco J; Martínez, Alfredo; Ramírez, María J

2018-03-29

Neurodegenerative diseases represent a heterogeneous group of disorders whose common characteristic is the progressive degeneration of neuronal structure and function. Although much knowledge has been accumulated on the pathophysiology of neurodegenerative diseases over the years, more efforts are needed to understand the processes that underlie these diseases and hence to propose new treatments. Adrenomedullin (AM) is a multifunctional peptide involved in vasodilation, hormone secretion, antimicrobial defense, cellular growth, and angiogenesis. In neurons, AM and related peptides are associated with some structural and functional cytoskeletal proteins that interfere with microtubule dynamics. Furthermore, AM may intervene in neuronal dysfunction through other mechanisms such as immune and inflammatory response, apoptosis, or calcium dyshomeostasis. Alterations in AM expression have been described in neurodegenerative processes such as Alzheimer's disease or vascular dementia. This review addresses the current state of knowledge on AM and its possible implication in neurodegenerative diseases.

Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

PubMed

Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

2016-09-01

OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

Predictors of First-Onset Substance Use Disorders During the Prospective Course of Bipolar Spectrum Disorders in Adolescents

PubMed Central

Goldstein, Benjamin I.; Strober, Michael; Axelson, David; Goldstein, Tina R.; Gill, Mary Kay; Hower, Heather; Dickstein, Daniel; Hunt, Jeffrey; Yen, Shirley; Kim, Eunice; Ha, Wonho; Liao, Fangzi; Fan, Jieyu; Iyengar, Satish; Ryan, Neal D.; Keller, Martin B.; Birmaher, Boris

2013-01-01

Objective Substance use disorders (SUD) are common and problematic in bipolar disorder (BP). We prospectively examined predictors of first-onset SUD among adolescents with BP. Method Adolescents (12–17 years old; N=167) in the Course and Outcome of Bipolar Youth (COBY) study fulfilling criteria for BP-I, BP-II, or operationalized BP not otherwise specified, without SUD at intake, were included. Baseline demographic, clinical, and family history variables, and clinical variables assessed during follow-up, were examined in relation to first-onset SUD. Participants were prospectively interviewed every 38.5±22.2 weeks for an average of 4.25±2.11 years. Results First-onset SUD developed among 32% of subjects, after a mean of 2.7±2.0 years from intake. Lifetime alcohol experimentation at intake most robustly predicted first-onset SUD. Lifetime oppositional defiant disorder and panic disorder, family history of SUD, low family cohesiveness, and absence of antidepressant treatment at intake were also associated with increased risk of SUD, whereas BP subtype was not. Risk of SUD increased with increasing number of these six predictors: 54.7% of subjects with ≥3 predictors developed SUD vs. 14.1% of those with <3 predictors (Hazard Ratio 5.41 95% CI 2.7–11.0 p<0.0001). Greater hypo/manic symptom severity in the preceding 12 weeks predicted greater likelihood of SUD onset. Lithium exposure in the preceding 12 weeks predicted lower likelihood of SUD. Conclusions This study identifies several predictors of first-onset SUD in the COBY sample which, if replicated, may suggest targets of preventive interventions for SUD among youth with BP. Treatment-related findings are inconclusive and must be interpreted tentatively given the limitations of observational naturalistic treatment data. There is a substantial window of opportunity between BP and SUD onset during which preventive strategies may be employed. PMID:24074469

Optimizing mouse models of neurodegenerative disorders: are therapeutics in sight?

PubMed

Lutz, Cathleen M; Osborne, Melissa A

2013-01-01

The genomic and biologic conservation between mice and humans, along with our increasing ability to manipulate the mouse genome, places the mouse as a premier model for deciphering disease mechanisms and testing potential new therapies. Despite these advantages, mouse models of neurodegenerative disease are sometimes difficult to generate and can present challenges that must be carefully addressed when used for preclinical studies. For those models that do exist, the standardization and optimization of the models is a critical step in ensuring success in both basic research and preclinical use. This review looks back on the history of model development for neurodegenerative diseases and highlights the key strategies that have been learned in order to improve the design, development and use of mouse models in the study of neurodegenerative disease.

“Gambling disorder in older adults: a cross-cultural perspective”

PubMed Central

Medeiros, Gustavo Costa; Leppink, Eric; Yaemi, Ana; Mariani, Mirella; Tavares, Hermano; Grant, Jon

2015-01-01

INTRODUCTION Gambling Disorder (GD) in older adults is significantly increasing and became an important public health issue in different countries. However, little is known regarding GD in older adults. The prevalence and acceptance of gambling varies among different cultures and this raises the question of how and to what extent culture affects older gamblers. The majority of the important studies regarding GD in older adults have been conducted mainly in Anglo-Saxon cultures and little information is available regarding GD in other cultures. The objective of this paper is to perform the first standardized cross-cultural comparison regarding older adults presenting GD. METHODS The total studied sample involved 170 subjects: 89 from the Brazilian (BR) sample and 81 from the American (US) sample. It consisted of 67 men and 103, women (average age = 64.42, standard deviation = ±3,86). They were evaluated for socio-demographics, gambling behavior variables and psychiatric antecedents. RESULTS Overall, there were significant differences between BR and US older adults gamblers in marital status, onset of gambling activity, onset of GD and urge scores. DISCUSSION This study showed that there are important differences in gambling course, gambling behavior and personal antecedents between two samples of older adults presenting GD from countries with different social-cultural background. It weakens the possibility of generalization of results found in Anglo-Saxon countries to other cultures and reinforces for the need for development of research on GD in older adults outside the Anglo-Saxon culture. PMID:25612901

The role of iron in neurodegenerative disorders: insights and opportunities with synchrotron light

PubMed Central

Collingwood, Joanna F.; Davidson, Mark R.

2014-01-01

There is evidence for iron dysregulation in many forms of disease, including a broad spectrum of neurodegenerative disorders. In order to advance our understanding of the pathophysiological role of iron, it is helpful to be able to determine in detail the distribution of iron as it relates to metabolites, proteins, cells, and tissues, the chemical state and local environment of iron, and its relationship with other metal elements. Synchrotron light sources, providing primarily X-ray beams accompanied by access to longer wavelengths such as infra-red, are an outstanding tool for multi-modal non-destructive analysis of iron in these systems. The micro- and nano-focused X-ray beams that are generated at synchrotron facilities enable measurement of iron and other transition metal elements to be performed with outstanding analytic sensitivity and specificity. Recent developments have increased the scope for methods such as X-ray fluorescence mapping to be used quantitatively rather than semi-quantitatively. Burgeoning interest, coupled with technical advances and beamline development at synchrotron facilities, has led to substantial improvements in resources and methodologies in the field over the past decade. In this paper we will consider how the field has evolved with regard to the study of iron in proteins, cells, and brain tissue, and identify challenges in sample preparation and analysis. Selected examples will be used to illustrate the contribution, and future potential, of synchrotron X-ray analysis for the characterization of iron in model systems exhibiting iron dysregulation, and for human cases of neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis. PMID:25191270

Effect of a Dissonance-Based Prevention Program on Risk for Eating Disorder Onset in the Context of Eating Disorder Risk Factors

PubMed Central

Rohde, Paul; Gau, Jeff; Shaw, Heather

2013-01-01

Test (a) whether a dissonance-based eating disorder prevention program that reduces thin-ideal internalization mitigates the effects of risk factors for eating disorder onset and (b) whether the risk factors moderate the effects of this intervention on risk for eating disorder onset, to place the effects of this intervention within the context of established risk factors. Female adolescents (N=481) with body image concerns were randomized to the dissonance-based program, healthy weight control program, expressive writing control condition, or assessment-only control condition. Denial of costs of pursuing the thin-ideal was the most potent risk factor for eating disorder onset during the 3-year follow-up (OR=5.0). The dissonance program mitigated the effect of this risk factor. For participants who did not deny costs of pursuing the thin-ideal, emotional eating and externalizing symptoms increased risk for eating disorder onset. Negative affect attenuated the effects of each of the active interventions in this trial. Results imply that this brief prevention program offsets the risk conveyed by the most potent risk factor for eating disorder onset in this sample, implicate three vulnerability pathways to eating pathology involving thin-ideal pursuit, emotional eating, and externalizing symptoms, and suggest that negative affect mitigates the effects of eating disorder prevention programs. PMID:21975593

[Molecular-targeted therapy for neurodegenerative diseases].

PubMed

Sobue, Gen

2009-11-01

Neurodegenerative diseases have been construed as incurable disorders. However, therapeutic development for these diseases is now facing a turning point: analyses of cellular and animal models have provided insights into pathogenesis of neurodegenerative diseases, and have indicated rational therapeutic approaches to them. Therefore, how to realize molecular targeted therapy for neurodegenerative diseases is becoming one of the most challenging issues in the clinical neurology. Primarily, pathophysiological understanding of the disease from basic science is the first step. For the successful clinical trials, effective trial design, sufficient economic and social support, and education are indispensable. The development of androgen deprivation therapy for spinal and bulbar muscular atrophy (SBMA) is a representative study in this field. SBMA is a hereditary neurodegenerative disease caused by expansion of a trinucleotide CAG repeat in the first exon of the androgen receptor (AR) gene. There is increasing evidence that testosterone, the ligand of AR, plays a pivotal role in the neurodegeneration in SBMA. The striking success of androgen deprivation therapy in SBMA mouse models has been translated into phase 2, and then phase 3, clinical trials.

Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials.

PubMed

Tortelli, Rosanna; Seripa, Davide; Panza, Francesco; Solfrizzi, Vincenzo; Logroscino, Giancarlo

2016-01-01

Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases. Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design. The same is true for genetic variants in cytochrome P450 (CYP), the principal enzymes influencing drug metabolism. A better characterization of individual genetic background may optimize clinical trial design and personal drug response. This chapter describes the state of the art about the impact of genetic factors in RCTs on neurodegenerative disease, with AD, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease as examples. Furthermore, a brief description of the genetic bases of drug response focusing on neurodegenerative diseases will be conducted. The role of pharmacogenetics in RCTs for neurodegenerative diseases is still a young, unexplored, and promising field. Genetic tools allow increased sophistication in patient profiling and treatment optimization. Pharmaceutical companies are aware of the value of collecting genetic data during their RCTs. Pharmacogenetic research is bidirectional with RCTs: efficacy data are correlated with genetic polymorphisms, which in turn define subjects for treatment stratification. © 2016 S. Karger AG, Basel.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Inflammatory mediators as biomarkers in brain disorders.

PubMed

Nuzzo, Domenico; Picone, Pasquale; Caruana, Luca; Vasto, Sonya; Barera, Annalisa; Caruso, Calogero; Di Carlo, Marta

2014-06-01

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases.

Eating disorders in older women: does late onset anorexia nervosa exist?

PubMed

Scholtz, Samantha; Hill, Laura S; Lacey, Hubert

2010-07-01

The objective of this study is to determine whether eating disorders can present for the first time in older people. This is a descriptive study of patients above the age of 50 years who have presented to a national eating disorder center within the last 10 years. Thirty-two patients were identified; data were available for 26 of these patients and 11 agreed for further interview and questionnaire completion. There were no cases where the eating disorder had its onset late in life. Of the 11 interviewed, six participants retained a diagnosis of anorexia nervosa, four had Eating Disorder Not Otherwise Specified and only one was recovered. Comorbid depression was universal in those still suffering with an eating disorder diagnosis, and their level of social functioning was impaired. Anorexia nervosa is a chronic and enduring mental illness that, although rare, can be found in older people. In our sample, we found no evidence of late-onset disorders; all described cases were lifelong. 2009 by Wiley Periodicals, Inc.

Age at asthma onset and asthma self-management education among adults in the United States.

PubMed

Mirabelli, Maria C; Beavers, Suzanne F; Shepler, Samantha H; Chatterjee, Arjun B

2015-01-01

Asthma self-management education improves asthma-related outcomes. We conducted this analysis to evaluate variation in the percentages of adults with active asthma reporting components of asthma self-management education by age at asthma onset. Data from 2011 to 2012 Asthma Call-back Surveys were used to estimate percentages of adults with active asthma reporting six components of asthma self-management education. Components of asthma self-management education include having been taught to what to do during an asthma attack and receiving an asthma action plan. Differences in the percentages of adults reporting each component and the average number of components reported across categories of age at asthma onset were estimated using linear regression, adjusted for age, education, race/ethnicity, sex, smoking status, and years since asthma onset. Overall, an estimated 76.4% of adults with active asthma were taught what to do during an asthma attack and 28.7% reported receiving an asthma action plan. Percentages reporting each asthma self-management education component declined with increasing age at asthma onset. Compared with the referent group of adults whose asthma onset occurred at 5-14 years of age, the percentage of adults reporting being taught what to do during an asthma attack was 10% lower among those whose asthma onset occurred at 65-93 years of age (95% CI: -18.0, -2.5) and the average number of components reported decreased monotonically across categories of age at asthma onset of 35 years and older. Among adults with active asthma, reports of asthma self-management education decline with increasing age at asthma onset.

The experience of living with adult-onset epilepsy.

PubMed

Kılınç, Stephanie; van Wersch, Anna; Campbell, Carol; Guy, Alison

2017-08-01

The incidence and prevalence of adults diagnosed with epilepsy is higher compared to those diagnosed in childhood, yet the experience of living with adult-onset epilepsy has rarely been examined. Hence, the current study took a phenomenological approach to examining the experience of living with epilepsy following diagnosis in adulthood. Semi-structured interviews were conducted with 39 people from across the UK, diagnosed with epilepsy between the ages of eighteen and sixty, at two points in time, six months apart. Phenomenological analysis identified three central themes: the unpredictability of seizure occurrence; the ripple effect; and re-evaluating the future. Despite the accepted consensus in the epilepsy literature that living and coping with epilepsy becomes more difficult the older a person is diagnosed, the current findings indicated that this is inadequate. Rather, it is more suitable to consider that those living with adult-onset epilepsy have a specific experience of the condition and particular support needs, given that they once lived their lives as people without epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

ERIC Educational Resources Information Center

Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

2012-01-01

Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

Neuropsychological Functioning in Childhood-Onset Psychosis and Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Brodsky, Kimberly; Willcutt, Erik G.; Davalos, Deana B.; Ross, Randal G.

2014-01-01

Background: Attention-deficit/hyperactivity disorder (ADHD) and childhood-onset psychosis (COP) are chronic, heterogeneous disorders with symptoms that frequently co-occur, but the etiology of their comorbidity is unknown. Studies of each disorder indicate that both ADHD and COP are associated with a range of neuropsychological weaknesses, but few…

Repeat expansion and autosomal dominant neurodegenerative disorders: consensus and controversy.

PubMed

Rudnicki, Dobrila D; Margolis, Russell L

2003-08-22

Repeat-expansion mutations cause 13 autosomal dominant neurodegenerative disorders falling into three groups. Huntington's disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and spinocerebellar ataxias (SCAs) types 1, 2, 3, 7 and 17 are each caused by a CAG repeat expansion that encodes polyglutamine. Convergent lines of evidence demonstrate that neurodegeneration in these diseases is a consequence of the neurotoxic effects of abnormally long stretches of glutamines. How polyglutamine induces neurodegeneration, and why neurodegeneration occurs in only select neuronal populations, remains a matter of intense investigation. SCA6 is caused by a CAG repeat expansion in CACNA1A, a gene that encodes a subunit of the P/Q-type calcium channel. The threshold length at which the repeat causes disease is much shorter than in the other polyglutamine diseases, and neurodegeneration may arise from expansion-induced change of function in the calcium channel. Huntington's disease-like 2 (HDL2) and SCAs 8, 10 and 12 are rare disorders in which the repeats (CAG, CTG or ATTCT) are not in protein-coding regions. Investigation into these diseases is still at an early stage, but it is now reasonable to hypothesise that the net effect of each expansion is to alter gene expression. The different pathogenic mechanisms in these three groups of diseases have important implications for the development of rational therapeutics.

Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

PubMed Central

Shen, Guohua; Zhang, Yuwei; Hu, Shuang; Liu, Bin; Kuang, Anren

2017-01-01

Abstract Rationale: Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. Patient concerns: A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Diagnoses, interventions and outcomes: Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. Lessons: HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms. PMID:28353596

Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

PubMed

Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

2018-01-01

We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

PubMed

Sikich, Linmarie; Frazier, Jean A; McClellan, Jon; Findling, Robert L; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2008-11-01

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia

Fathers' Alcohol and Cannabis Use Disorder and Early Onset of Drug Use by Their Children.

PubMed

Henry, Kimberly L

2017-05-01

The unique influence of fathers' alcohol and cannabis use disorder on children's onset of use of these same substances has been rarely studied. A clear understanding of family history in this context is important for the development of family-based prevention initiatives aimed at delaying the onset of substance use among children. Prospective, longitudinal, and intergenerational data on 274 father-child dyads were used. Logistic regression models were estimated to assess the association between fathers' lifetime incidence of an alcohol and cannabis use disorder and children's onset of use of these same substances at or before age 15. The children of fathers who met the criteria for a lifetime cannabis use disorder were more likely to initiate use of alcohol (odds ratio = 6.71, 95% CI [1.92, 23.52]) and cannabis (odds ratio = 8.13, 95% CI [2.07, 31.95]) by age 15, when background covariates and presence of a lifetime alcohol use disorder were controlled for. No unique effect of fathers' alcohol use disorder on children's onset of alcohol and cannabis use was observed. Fathers' lifetime cannabis use disorder had a unique and robust association with children's uptake of alcohol and cannabis by age 15. Future research is needed to identify the mediating mechanisms that link fathers' disorder with children's early onset.

Vitrectomy for full-thickness macular hole in adult-onset Coats’ disease

PubMed Central

Kumar, Vinod; Kumar, Pradeep; Garg, Gaurav; Damodaran, Saurabh

2017-01-01

The occurrence of full thickness macular hole in Coats’ disease is extremely rare. The purpose of this case report is to report pars plana vitrectomy for the treatment of full thickness macular hole in a patient with adult onset Coats disease. A young male presented with decreased vision in his right eye because of full thickness macular hole. The macular hole was found to be associated with adult onset Coats’ disease that was evident on ultra-wide field imaging. The patient underwent laser photocoagulation to the vascular telangiectasia followed by pars plana vitrectomy, large internal limiting membrane peeling and gas tamponade. This resulted in regression of exudation, closure of macular hole and improvement in vision. Coats disease of adult onset can present with decreased vision because of full thickness macular hole. Vitrectomy with internal limiting membrane peeling can result in excellent visual outcome. PMID:29133668

Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism.

PubMed

Martin, Andrew T; Pinney, Susan M; Xie, Changchun; Herrick, Robert L; Bai, Yun; Buckholz, Jeanette; Martin, Vincent T

2017-01-01

To determine whether headache disorders are a risk factor for the development of new onset hypothyroidism. Past studies have reported associations between headache disorders and hypothyroidism, but the directionality of the association is unknown. This was a longitudinal retrospective cohort study using data from the Fernald Medical Monitoring Program (FMMP). Residents received physical examinations and thyroid function testing every 3 years during the 20 year program. Residents were excluded from the cohort if there was evidence of past thyroid disease or abnormal thyroid function tests at the first office visit. A diagnosis of a headache disorder was established by self-report of "frequent headaches," use of any headache-specific medication, or a physician diagnosis of a headache disorder. The primary outcome measure was new onset hypothyroidism defined as the initiation of thyroid replacement therapy or TSH ≥ 10 without thyroid medication. A Cox survival analysis with time dependent variables were used for the model. Headache disorders, age, sex, body mass index, income, smoking, narcotic use, and hypothyroidism-producing medications were independent variables in the model. Data from 8412 residents enrolled in the FMMP were used in the current study. Headache disorders were present in about 26% of the residents and new onset hypothyroidism developed in ∼7%. The hazard ratio for the development of new onset hypothyroidism was 1.21 (95% CI = 1.001, 1.462) for those with headache disorders. Headache disorders may be associated with an increased risk for the development of new onset hypothyroidism. © 2016 American Headache Society.

Don't panic: interpretation bias is predictive of new onsets of panic disorder.

PubMed

Woud, Marcella L; Zhang, Xiao Chi; Becker, Eni S; McNally, Richard J; Margraf, Jürgen

2014-01-01

Psychological models of panic disorder postulate that interpretation of ambiguous material as threatening is an important maintaining factor for the disorder. However, demonstrations of whether such a bias predicts onset of panic disorder are missing. In the present study, we used data from the Dresden Prediction Study, in which a epidemiologic sample of young German women was tested at two time points approximately 17 months apart, allowing the study of biased interpretation as a potential risk factor. At time point one, participants completed an Interpretation Questionnaire including two types of ambiguous scenarios: panic-related and general threat-related. Analyses revealed that a panic-related interpretation bias predicted onset of panic disorder, even after controlling for two established risk factors: anxiety sensitivity and fear of bodily sensations. This is the first prospective study demonstrating the incremental validity of interpretation bias as a predictor of panic disorder onset. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stabilization in early adult-onset myopia with corneal refractive therapy.

PubMed

González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

2016-02-01

To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal Correctional Clients.

PubMed

DeLisi, Matt; Tahja, Katherine N; Drury, Alan J; Elbert, Michael J; Caropreso, Daniel E; Heinrichs, Timothy

2018-01-01

Adult antisocial behavior is almost always predated by delinquency during childhood or adolescence; however, there is also evidence of adult-onset criminal offending. This study examined this controversial subgroup of offenders using self-reported and official data from a total population of federal correctional clients selected from the Midwestern United States. Difference of means t-tests, chi-square tests, and logistic regression models found that 11.7% of clients had an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring at age 60 years or older. This group-introduced as de novo advanced adult-onset offenders-had high socioeconomic status, mixed evidence of adverse childhood experiences, and virtually no usage of drugs with the exception of alcohol. These offenders were primarily convicted of social security and white-collar crimes and evinced remarkably low psychopathology and criminal risk. More research is needed to replicate the phenomenon of de novo advanced adult-onset offending. © 2017 American Academy of Forensic Sciences.

Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

PubMed

Esopenko, Carrie; Levine, Brian

2015-02-15

Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

Admixture analysis of age at onset in first episode bipolar disorder.

PubMed

Nowrouzi, Behdin; McIntyre, Roger S; MacQueen, Glenda; Kennedy, Sidney H; Kennedy, James L; Ravindran, Arun; Yatham, Lakshmi; De Luca, Vincenzo

2016-09-01

Many studies have used the admixture analysis to separate age-at-onset (AAO) subgroups in bipolar disorder, but none of them examined first episode patients. The purpose of this study was to investigate the influence of clinical variables on AAO in first episode bipolar patients. The admixture analysis was applied to identify the model best fitting the observed AAO distribution of a sample of 194 patients with DSM-IV diagnosis of bipolar disorder and the finite mixture model was applied to assess the effect of clinical covariates on AAO. Using the BIC method, the model that was best fitting the observed distribution of AAO was a mixture of three normal distributions. We identified three AAO groups: early age-at-onset (EAO) (µ=18.0, σ=2.88), intermediate-age-at-onset (IAO) (µ=28.7, σ=3.5), and late-age-at-onset (LAO) (µ=47.3, σ=7.8), comprising 69%, 22%, and 9% of the sample respectively. Our first episode sample distribution model was significantly different from most of the other studies that applied the mixture analysis. The main limitation is that our sample may have inadequate statistical power to detect the clinical associations with the AAO subgroups. This study confirms that bipolar disorder can be classified into three groups based on AAO distribution. The data reported in our paper provide more insight into the diagnostic heterogeneity of bipolar disorder across the three AAO subgroups. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular underpinnings of neurodegenerative disorders: striatal-enriched protein tyrosine phosphatase signaling and synaptic plasticity

PubMed Central

Lombroso, Paul J.; Ogren, Marilee; Kurup, Pradeep; Nairn, Angus C.

2016-01-01

This commentary focuses on potential molecular mechanisms related to the dysfunctional synaptic plasticity that is associated with neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Specifically, we focus on the role of striatal-enriched protein tyrosine phosphatase (STEP) in modulating synaptic function in these illnesses. STEP affects neuronal communication by opposing synaptic strengthening and does so by dephosphorylating several key substrates known to control synaptic signaling and plasticity. STEP levels are elevated in brains from patients with Alzheimer’s and Parkinson’s disease. Studies in model systems have found that high levels of STEP result in internalization of glutamate receptors as well as inactivation of ERK1/2, Fyn, Pyk2, and other STEP substrates necessary for the development of synaptic strengthening. We discuss the search for inhibitors of STEP activity that may offer potential treatments for neurocognitive disorders that are characterized by increased STEP activity. Future studies are needed to examine the mechanisms of differential and region-specific changes in STEP expression pattern, as such knowledge could lead to targeted therapies for disorders involving disrupted STEP activity. PMID:29098072

Nature, nurture and neurology: gene-environment interactions in neurodegenerative disease. FEBS Anniversary Prize Lecture delivered on 27 June 2004 at the 29th FEBS Congress in Warsaw.

PubMed

Spires, Tara L; Hannan, Anthony J

2005-05-01

Neurodegenerative disorders, such as Huntington's, Alzheimer's, and Parkinson's diseases, affect millions of people worldwide and currently there are few effective treatments and no cures for these diseases. Transgenic mice expressing human transgenes for huntingtin, amyloid precursor protein, and other genes associated with familial forms of neurodegenerative disease in humans provide remarkable tools for studying neurodegeneration because they mimic many of the pathological and behavioural features of the human conditions. One of the recurring themes revealed by these various transgenic models is that different diseases may share similar molecular and cellular mechanisms of pathogenesis. Cellular mechanisms known to be disrupted at early stages in multiple neurodegenerative disorders include gene expression, protein interactions (manifesting as pathological protein aggregation and disrupted signaling), synaptic function and plasticity. Recent work in mouse models of Huntington's disease has shown that enriching the environment of transgenic animals delays the onset and slows the progression of Huntington's disease-associated motor and cognitive symptoms. Environmental enrichment is known to induce various molecular and cellular changes in specific brain regions of wild-type animals, including altered gene expression profiles, enhanced neurogenesis and synaptic plasticity. The promising effects of environmental stimulation, demonstrated recently in models of neurodegenerative disease, suggest that therapy based on the principles of environmental enrichment might benefit disease sufferers and provide insight into possible mechanisms of neurodegeneration and subsequent identification of novel therapeutic targets. Here, we review the studies of environmental enrichment relevant to some major neurodegenerative diseases and discuss their research and clinical implications.

Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder.

PubMed

Boeve, B F; Silber, M H; Ferman, T J; Lin, S C; Benarroch, E E; Schmeichel, A M; Ahlskog, J E; Caselli, R J; Jacobson, S; Sabbagh, M; Adler, C; Woodruff, B; Beach, T G; Iranzo, A; Gelpi, E; Santamaria, J; Tolosa, E; Singer, C; Mash, D C; Luca, C; Arnulf, I; Duyckaerts, C; Schenck, C H; Mahowald, M W; Dauvilliers, Y; Graff-Radford, N R; Wszolek, Z K; Parisi, J E; Dugger, B; Murray, M E; Dickson, D W

2013-08-01

To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative

Innate immune activation in neurodegenerative disease.

PubMed

Heneka, Michael T; Kummer, Markus P; Latz, Eicke

2014-07-01

The triggering of innate immune mechanisms is emerging as a crucial component of major neurodegenerative diseases. Microglia and other cell types in the brain can be activated in response to misfolded proteins or aberrantly localized nucleic acids. This diverts microglia from their physiological and beneficial functions, and leads to their sustained release of pro-inflammatory mediators. In this Review, we discuss how the activation of innate immune signalling pathways - in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome - by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders. During chronic activation of microglia, the sustained exposure of neurons to pro-inflammatory mediators can cause neuronal dysfunction and contribute to cell death. As chronic neuroinflammation is observed at relatively early stages of neurodegenerative disease, targeting the mechanisms that drive this process may be useful for diagnostic and therapeutic purposes.

Cerebral vasomotor reactivity in neurodegenerative diseases.

PubMed

Smoliński, Łukasz; Członkowska, Anna

Small-caliber cerebral vessels change their diameters in response to alterations of key metabolite concentrations such as carbon dioxide or oxygen. This phenomenon, termed the cerebral vasomotor reactivity (CVMR), is the basis for blood flow regulation in the brain in accordance with its metabolic status. Typically, CVMR is determined as the amount of change in cerebral blood flow in response to a vasodilating stimulus, which can be measured by various neuroimaging methods or by transcranial Doppler. It has been shown that CVMR is impaired in cerebrovascular diseases, but there is also evidence of a similar dysfunction in neurodegenerative disorders. Here, we review studies that have investigated CVMR in the common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Moreover, we discuss potential neurodegenerative mechanisms responsible for the impairment of CVMR. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care.

PubMed

Yamada, Shigeki; Ishikawa, Masatsune; Yamamoto, Kazuo

2017-01-01

In spite of growing evidence of idiopathic normal-pressure hydrocephalus (NPH), a viewpoint about clinical care for idiopathic NPH is still controversial. A continuous divergence of viewpoints might be due to confusing classifications of idiopathic and adult-onset congenital NPH. To elucidate the classification of NPH, we propose that adult-onset congenital NPH should be explicitly distinguished from idiopathic and secondary NPH. On the basis of conventional CT scan or MRI, idiopathic NPH was defined as narrow sulci at the high convexity in concurrent with enlargement of the ventricles, basal cistern and Sylvian fissure, whereas adult-onset congenital NPH was defined as huge ventricles without high-convexity tightness. We compared clinical characteristics and cerebrospinal fluid distribution among 85 patients diagnosed with idiopathic NPH, 17 patients with secondary NPH, and 7 patients with adult-onset congenital NPH. All patients underwent 3-T MRI examinations and tap-tests. The volumes of ventricles and subarachnoid spaces were measured using a 3D workstation based on T2-weighted 3D sequences. The mean intracranial volume for the patients with adult-onset congenital NPH was almost 100 mL larger than the volumes for patients with idiopathic and secondary NPH. Compared with the patients with idiopathic or secondary NPH, patients with adult-onset congenital NPH exhibited larger ventricles but normal sized subarachnoid spaces. The mean volume ratio of the high-convexity subarachnoid space was significantly less in idiopathic NPH than in adult-onset congenital NPH, whereas the mean volume ratio of the basal cistern and Sylvian fissure in idiopathic NPH was >2 times larger than that in adult-onset congenital NPH. The symptoms of gait disturbance, cognitive impairment, and urinary incontinence in patients with adult-onset congenital NPH tended to progress more slowly compared to their progress in patients with idiopathic NPH. Cerebrospinal fluid distributions and

Pathological Personality Traits and the Naturalistic Course of Internalizing Disorders among High-Risk Young Adults

PubMed Central

Conway, Christopher C.; Craske, Michelle G.; Zinbarg, Richard E.; Mineka, Susan

2015-01-01

Background A diagnosis of personality disorder (PD) signals a negative prognosis for depressive and anxiety disorders, but the precise abnormal personality traits that regulate the temporal course of internalizing psychopathology are unknown. In the present study, we examined prospective associations between abnormal personality traits and the onset and recurrence of internalizing disorders. Methods A sample of 371 young adults at high risk for internalizing problems completed the Schedule for Nonadaptive and Adaptive Personality-Second Edition—a measure of 12 abnormal personality traits and three temperament dimensions (i.e., Negative Temperament, Positive Temperament, Disinhibition versus Control)—and underwent annual diagnostic interviews over four years of follow-up. Results In multivariate survival analyses, Negative Temperament was a robust predictor of both new onsets and recurrences of internalizing disorder. Further, the Dependency and Self-Harm abnormal personality dimensions emerged as independent predictors of new onsets and recurrences, respectively, of internalizing disorders after statistically adjusting for variation in temperament. Conclusions Our findings suggest that abnormal personality traits and temperament dimensions have complementary effects on the trajectory of internalizing pathology during young adulthood. In assessment and treatment settings, targeting the abnormal personality and temperament dimensions with the greatest prognostic value stands to improve the early detection of enduring internalizing psychopathology. PMID:26344411

PATHOLOGICAL PERSONALITY TRAITS AND THE NATURALISTIC COURSE OF INTERNALIZING DISORDERS AMONG HIGH-RISK YOUNG ADULTS.

PubMed

Conway, Christopher C; Craske, Michelle G; Zinbarg, Richard E; Mineka, Susan

2016-01-01

A personality disorder diagnosis signals a negative prognosis for depressive and anxiety disorders, but the precise abnormal personality traits that determine the temporal course of internalizing psychopathology are unknown. In the present study, we examined prospective associations between abnormal personality traits and the onset and recurrence of internalizing disorders. A sample of 371 young adults at high risk for internalizing problems completed the Schedule for Nonadaptive and Adaptive Personality-Second Edition--a measure of 12 abnormal personality traits and three temperament dimensions (i.e., Negative Temperament, Positive Temperament, Disinhibition vs. Control)--and underwent annual diagnostic interviews over 4 years of follow-up. In multivariate survival analyses, Negative Temperament was a robust predictor of both new onsets and recurrences of internalizing disorder. Further, the Dependency and Self-Harm abnormal personality dimensions emerged as independent predictors of new onsets and recurrences, respectively, of internalizing disorders after statistically adjusting for variation in temperament. Our findings suggest that abnormal personality traits and temperament dimensions have complementary effects on the trajectory of internalizing pathology during young adulthood. In assessment and treatment settings, targeting the abnormal personality and temperament dimensions with the greatest prognostic value stands to improve the early detection of enduring internalizing psychopathology. © 2015 Wiley Periodicals, Inc.

Adult onset Leigh syndrome with mitochondrial DNA 8344 A>G mutation.

PubMed

Han, Jee-Young; Sung, Jung-Joon; Park, Hong-Kyun; Yoon, Byung-Nam; Lee, Kwang-Woo

2014-11-01

We report a pedigree of adult-onset Leigh syndrome (LS) with mitochondrial mutation 8344 A>G. A 38-year-old woman presented with optic neuropathy, weakness and cognitive impairment. Family history of optic neuropathy and systemic involvement was suggestive of mitochondrial encephalopathy. Genetic and radiologic studies showed m.8344 A>G mutation with characteristics of LS. To our knowledge this is the first case of adult-onset LS demonstrating the m.8344 A>G mutation. Copyright © 2014 Elsevier Ltd. All rights reserved.

REWARD ENHANCES TIC SUPPRESSION IN CHILDREN WITHIN MONTHS OF TIC DISORDER ONSET

PubMed Central

Greene, Deanna J.; Koller, Jonathan M.; Robichaux-Viehoever, Amy; Bihun, Emily C.; Schlaggar, Bradley L.; Black, Kevin J.

2014-01-01

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic. PMID:25220075

Adult Attention-Deficit / Hyperactivity Disorder (ADHD)

MedlinePlus

Adult attention-deficit/hyperactivity disorder (ADHD) Overview Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that ... combination of persistent problems, such as difficulty paying attention, hyperactivity and impulsive behavior. Adult ADHD can lead ...

Preceding diagnoses to young adult bipolar disorder and schizophrenia in a nationwide study

PubMed Central

2013-01-01

Background The aim of this comparative study was to investigate the type and frequency of diagnoses preceding adult bipolar disorder (BD) and schizophrenia (SZ). Methods A follow-back study of all preceding diagnoses in all patients aged 21–34 years with a primary, first time diagnosis of BD (N = 784) or SZ (N = 1667) in 2008 to 2010. Data were taken from the Danish Psychiatric Central Research Register (DPCRR) including ICD-10 and ICD-8 diagnoses. Results The numbers of patients with any preceding diagnoses amounted to 69.3% in BD and 76.6% in SZ with affective disorders (excluding BD) being the most frequent preceding diagnosis (46.6 vs. 28.0%), followed by psychoses (PSY) other than SZ (14.2 vs. 41.5%, p < .001), and substance use disorders (SUD) (16.1 vs. 26.9%, p < .001). Reactions to severe stress were equally frequent in both samples (26.3 vs. 26.6%) as were personality disorders (21.8 vs. 22.4%) and ADHD (4.2 vs. 3.5%), whereas rates of conduct disorders (1.7 vs. 3.1%) were rather low in both samples. Very few of the preceding diagnoses had their onset in childhood and adolescence. Overall patients with SZ had a minor but statistically significant earlier onset of any psychiatric disorder compared to BD (mean age: 23.3 vs. 22.5, p < .001). Regression analyses indicated that BD was associated with an increased risk of having experienced preceding affective disorders and ADHD, while SZ was associated with an increased risk of preceding substance use disorders, psychosis, anxiety disorders, and personality disorders. Conclusions Specific developmental trajectories of preceding disorders were delineated for BD and SZ with affective disorders being more specific for BD and both SUD and PSY more specific to SZ. There are different patterns of vulnerability in terms of preceding diagnosis in young adults with BD and SZ. PMID:24359146

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

PubMed

Bauer, Michael; Glenn, Tasha; Alda, Martin; Andreassen, Ole A; Angelopoulos, Elias; Ardau, Raffaella; Baethge, Christopher; Bauer, Rita; Bellivier, Frank; Belmaker, Robert H; Berk, Michael; Bjella, Thomas D; Bossini, Letizia; Bersudsky, Yuly; Cheung, Eric Yat Wo; Conell, Jörn; Del Zompo, Maria; Dodd, Seetal; Etain, Bruno; Fagiolini, Andrea; Frye, Mark A; Fountoulakis, Kostas N; Garneau-Fournier, Jade; González-Pinto, Ana; Harima, Hirohiko; Hassel, Stefanie; Henry, Chantal; Iacovides, Apostolos; Isometsä, Erkki T; Kapczinski, Flávio; Kliwicki, Sebastian; König, Barbara; Krogh, Rikke; Kunz, Mauricio; Lafer, Beny; Larsen, Erik R; Lewitzka, Ute; Lopez-Jaramillo, Carlos; MacQueen, Glenda; Manchia, Mirko; Marsh, Wendy; Martinez-Cengotitabengoa, Mónica; Melle, Ingrid; Monteith, Scott; Morken, Gunnar; Munoz, Rodrigo; Nery, Fabiano G; O'Donovan, Claire; Osher, Yamima; Pfennig, Andrea; Quiroz, Danilo; Ramesar, Raj; Rasgon, Natalie; Reif, Andreas; Ritter, Philipp; Rybakowski, Janusz K; Sagduyu, Kemal; Scippa, Ângela M; Severus, Emanuel; Simhandl, Christian; Stein, Dan J; Strejilevich, Sergio; Sulaiman, Ahmad Hatim; Suominen, Kirsi; Tagata, Hiromi; Tatebayashi, Yoshitaka; Torrent, Carla; Vieta, Eduard; Viswanath, Biju; Wanchoo, Mihir J; Zetin, Mark; Whybrow, Peter C

2014-01-01

The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. Recall bias for onset and family history data. A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Omental transplantation for neurodegenerative diseases.

PubMed

Rafael, Hernando

2014-01-01

Up to date, almost all researchers consider that there is still no effective therapy for neurodegenerative diseases (NDDs) and therefore, these diseases are incurable. However, since May 1998, we know that a progressive ischemia in the medial temporal lobes and subcommissural regions can cause Alzheimer's disease; because, in contrast to this, its revascularization by means of omental tissue can cure or improve this disease. Likewise we observed that the aging process, Huntington's disease, Parkinson's disease, and Amyotrophic lateral sclerosis; all of them are of ischemic origin caused by cerebral atherosclerosis, associated with vascular anomalies and/or environmental chemicals. On the contrary, an omental transplantation on the affected zone can stop and improve these diseases. For these reasons, I believe that NDDs, are wrongly classified as neurodegenerative disorders.

Association between mandibular retrognathia and TMJ disorders in adult females.

PubMed

Miller, James R; Burgess, Jeffrey A; Critchlow, Cathy W

2004-01-01

This study assesses the association between temporomandibular joint (TMJ) disorders and mandibular retrognathia. We conducted a case-control study among women, aged 18-70 years, recruited from Kaiser Permanente Northwest Division (KPNW, Portland, OR) and Group Health Cooperative of Puget Sound (GHC, Seattle, WA). Cases (N= 160) were women seeking treatment for TMJ disorders at KPNW and GHC clinics. Controls (N=151) were women without TMJ disorders, selected from among adult female dental hygiene patients at KPNW or GHC enrollees. Case status was determined by questionnaire; mandibular sagittal position (orthognathic, mildly retrognathic, severely retrognathic, or prognathic) was measured using digitized facial photographs. Odds ratios (OR) and associated 95 percent confidence intervals (CI) estimated the magnitude of the association between TMJ disorders and mandibular sagittal position. Women with TMJ disorders were 4.0 times (95% CI=1.5, 10.8) more likely than controls to have severe retrognathia; no association with mild retrognathia or prognathia was seen. Results were similar when cases were restricted to those with recent onset of TMJ pain (OR=6.3; 95% CI=1.8, 21.8). We found a strong association between TMJ disorders and severe mandibular retrognathia in adult females. In some women this likely resulted from TMJ disorders influencing mandibular development over time. However, among a subset of women, our data support the reverse hypothesis--that severe mandibular retrognathia may influence the development of TMJ disorders. Despite this strong association, abnormal mandibular position contributed only a small portion to the overall rate at which women sought treatment for TMJ disorders.

Posttraumatic stress disorder in adult attention-deficit/hyperactivity disorder: clinical features and familial transmission.

PubMed

Antshel, Kevin M; Kaul, Prashant; Biederman, Joseph; Spencer, Thomas J; Hier, Bridget O; Hendricks, Kaitlin; Faraone, Stephen V

2013-03-01

did not differ in core symptoms of ADHD nor in age at onset, but those with ADHD + PTSD had higher rates of psychiatric comorbidity than those with ADHD only (including higher lifetime rates of major depressive disorder, oppositional defiant disorder, social phobia, agoraphobia, and generalized anxiety disorder) and worse quality of life ratings for all domains. Familial risk analysis revealed that relatives of ADHD probands without PTSD had elevated rates of both ADHD (51%) and PTSD (12%) that significantly differed from rates among relatives of controls (7% [P ≤ .001] and 0% [P ≤ .05], respectively). A similar pattern of elevated risk for ADHD and PTSD (80% and 40%) was observed in relatives of probands with ADHD + PTSD (P ≤ .001 for both conditions). The comorbidity of PTSD and ADHD in adults leads to greater clinical severity in terms of psychiatric comorbidity and psychosocial functioning. The familial coaggregation of the 2 disorders suggests that these disorders share familial risk factors and that their co-occurrence is not due to diagnostic errors. © Copyright 2013 Physicians Postgraduate Press, Inc.

Premorbid Risk Factors for Major Depressive Disorder: Are They Associated With Early Onset and Recurrent Course?

PubMed Central

Wilson, Sylia; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

2014-01-01

Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age-11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual SNP-based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early-onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset. PMID:25422974

Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder.

PubMed

Walker, Daniel J; Mason, Oren; Clemow, David B; Day, Kathleen A

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a CNS disorder that has its onset in childhood, but often persists into adulthood. There is growing recognition that adult ADHD can result in multiple negative consequences for individuals. ADHD is also often associated with a number of comorbid psychiatric disorders. Atomoxetine (ATX), a nonstimulant, selective noradrenergic reuptake inhibitor, was approved in the United States in 2002 for the treatment of ADHD in children and adolescents, as well as adults. We review here the safety and efficacy of ATX in adults with ADHD, including data in special populations, functional outcomes, as well as provider and patient real-world perceptions. We searched the databases Embase, MEDLINE and PsycINFO using the terms 'ADHD' and 'adult' and 'ATX' capturing publications from January 1, 1998, to March 27, 2014. Only publications in English were considered. ATX demonstrated significantly greater improvement than placebo (PBO) on the Conners Adult ADHD Rating Scale-Investigator rated:Screening Version (CAARS-Inv:SV) in all trials (N = 6; total score difference ranged from -3.5 to -5.5). For long-term trials using the CAARS-Inv:SV, ATX demonstrated significantly greater improvement than PBO in three of four trials (total score differences ranged from -0.1 to -6.0). In short-term studies, ATX showed significantly greater improvement than PBO on the Adult ADHD Quality-of-Life scale total score in three of three studies, but results were mixed on the Sheehan Disability Scale. Three studies of ATX have reported statistically significant improvement (compared with PBO) on the Behavior Rating Inventory of Executive Function-Adult Version Self Report scale. The most common adverse events (occurring in ≥ 10% of patients taking ATX) were nausea, dry mouth, decreased appetite, insomnia and fatigue. ATX is an important treatment option for the right patient. ATX can provide long-term, consistent symptom relief and functional improvement

Associations between DSM-IV mental disorders and onset of self-reported peptic ulcer in the World Mental Health Surveys

PubMed Central

Scott, Kate M.; Alonso, Jordi; de Jonge, Peter; Viana, Maria Carmen; Liu, Zhaorui; O’Neill, Siobhan; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Stein, Dan J.; Angermeyer, Matthias; Benjet, Corina; de Girolamo, Giovanni; Firuleasa, Ingrid-Laura; Hu, Chiyi; Kiejna, Andrzej; Kovess-Masfety, Viviane; Levinson, Daphna; Nakane, Yoshibumi; Piazza, Marina; Posada-Villa, José A.; Khalaf, Mohammad Salih; Lim, Carmen C. W.; Kessler, Ronald C.

2013-01-01

Objective Recent research demonstrating concurrent associations between mental disorders and peptic ulcers has renewed interest in links between psychological factors and ulcers. However, little is known about associations between temporally prior mental disorders and subsequent ulcer onset. Nor has the potentially confounding role of childhood adversities been explored. The objective of this study was to examine associations between a wide range of temporally prior DSM-IV mental disorders and subsequent onset of ulcer, without and with adjustment for mental disorder comorbidity and childhood adversities. Methods Face-to-face household surveys conducted in 19 countries (n=52,095; person years=2,096,486).The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Peptic ulcer onset was assessed in the same interview by self-report of physician’s diagnosis and year of diagnosis. Survival analyses estimated associations between first onset of mental disorders and subsequent ulcer onset. Results After comorbidity and sociodemographic adjustment, depression, social phobia, specific phobia, post-traumatic stress disorder, intermittent explosive disorder, alcohol and drug abuse disorders were significantly associated with ulcer onset (ORs 1.3-1.6). Increasing number of lifetime mental disorders was associated with ulcer onset in a dose-response fashion. These associations were only slightly attenuated by adjustment for childhood adversities. Conclusions A wide range of mental disorders were linked with the self-report of subsequent peptic ulcer onset. These associations require confirmation in prospective designs, but are suggestive of a role for mental disorders in contributing to ulcer vulnerability, possibly through abnormalities in the physiological stress response associated with mental disorders. PMID:23915767

The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder.

PubMed

Eisen, J L; Leonard, H L; Swedo, S E; Price, L H; Zabriskie, J B; Chiang, S Y; Karitani, M; Rasmussen, S A

2001-11-30

Compared with healthy control subjects, individuals with childhood-onset obsessive-compulsive disorder (OCD) have been reported to have a higher percentage of B cells that react with the monoclonal antibody D8/17, a marker for rheumatic fever. This study sought to replicate these findings in adults with OCD. Double-blind analyses of blood samples from 29 consecutive adults with primary OCD and 26 healthy control subjects were conducted to determine the percentage of B cells identified by D8/17. Using a standard criterion of > or =12% labeled B cells to denote positivity, rates of D8/17 positive individuals did not significantly differ between the OCD (58.6%) and control (42.3%) groups. Early age of onset was not a predictor of D8/17 positivity in the OCD group. The percentage of B cells identified by the monoclonal antibody marker D8/17 did not distinguish adults with OCD from control subjects, nor did it distinguish a sub-group of adults with OCD who described pre-pubertal onset of their OCD symptoms.

Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

ERIC Educational Resources Information Center

Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

2005-01-01

Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

PubMed

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Adult Hippocampal Neurogenesis, Aging and Neurodegenerative Diseases: Possible Strategies to Prevent Cognitive Impairment.

PubMed

Vivar, Carmen

2015-01-01

The adult brain of humans and other mammals continuously generates new neurons throughout life. However, this neurogenic capacity is limited to two brain areas, the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ of the lateral ventricle. Although the DG generates new neurons, its neurogenic capacity declines with age and neurodegenerative diseases such as Alzheimer's disease (AD and Huntington's disease (HD. This review focuses on the role of newly-born neurons in cognitive processes, and discusses some of the strategies proposed in humans and animals to enhance neurogenesis and counteract age-related cognitive deficits, such as physical exercise and intake of natural products like omega-3 fatty acids, curcumin and flavanols.

Reward enhances tic suppression in children within months of tic disorder onset.

PubMed

Greene, Deanna J; Koller, Jonathan M; Robichaux-Viehoever, Amy; Bihun, Emily C; Schlaggar, Bradley L; Black, Kevin J

2015-02-01

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment

PubMed Central

Li, Min; Wang, Li; Liu, Jiang-Hong; Zhan, Shu-Qin

2018-01-01

Objective: Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. Data Sources: Using the combined keywords: “RBD”, “neurodegenerative disease”, “Parkinson disease”, and “magnetic resonance imaging”, the PubMed/MEDLINE literature search was conducted up to January 1, 2018. Study Selection: A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. Results: Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. Conclusions: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated

Prevalence and clinical characteristics of adult-onset atopic dermatitis with positive skin prick testing to mites.

PubMed

Kulthanan, Kanokvalai; Chularojanamontri, Leena; Manapajon, Araya; Nuchkull, Piyavadee

2011-12-01

The clinical role of house dust mite (HDM) in atopic dermatitis (AD) is still controversial. The aim of the study is to assess the prevalence, clinical relevance and characteristics of adult-onset AD patients with positive skin prick tests (SPT) to mites. The case record forms of adult-onset AD patients who underwent SPT at the Skin Allergy Clinic, Siriraj Hospital were reviewed. Forty-one of 62 patients (66.1%) had positive SPT to mites. The frequency of intrinsic AD among adult-onset AD was 4.8% (3/62). SPT to HDM tended to be positive in patients who had personal or family history of atopy, positive SPT to several specific antigens or who presented with elevated serum IgE, chelitis, recurrent conjunctivitis and perifollicular accentuation, respectively. CONCLUSION The prevalence of adult-onset AD patients with mite sensitivity was high. There were some notable features that tended to be present in mite sensitive adult-onset AD patients.

Indian Herbs for the Treatment of Neurodegenerative Disease.

PubMed

Mannangatti, Padmanabhan; Naidu, Kamalakkannan Narasimha

2016-01-01

Ayurveda, an ancient system of medicine that is indigenous to India, is believed to be the world's oldest comprehensive health-care system and is now one of the most recognized and widely practiced disciplines of alternative medicine in the world. Medicinal herbs have been in use for treating diseases since ancient times in India. Ayurvedic therapies with medicinal herbs and herbomineral products generally provide relief without much adverse effects even after prolonged administration. Neurodegenerative disorders are a major cause of mortality and disability, and increasing life spans represent one of the key challenges of medical research. Ayurvedic medicine describes most neurodegenerative diseases and has defined a number of plants with therapeutic benefits for the treatment of neurodegenerative diseases having antioxidant activities. In this chapter, the role of four important Ayurvedic medicinal plants, viz., Withania somnifera (ashwagandha), Bacopa monnieri (brahmi), Centella asiatica (gotu kola), and Mucuna pruriens (velvet bean), on neurodegenerative diseases are discussed.

Childhood abuse, family history and stressors in older patients with bipolar disorder in relation to age at onset.

PubMed

Thesing, C S; Stek, M L; van Grootheest, D S; van de Ven, P M; Beekman, A T; Kupka, R W; Comijs, H C; Dols, A

2015-09-15

The aim of this study is to explore the family history of psychiatric disorders, childhood abuse, and stressors in older patients with Bipolar Disorder (BD) and the association of these variables with the age at onset of BD. The Questionnaire for Bipolar Disorder (QBP) and the Mini International Neuropsychiatric Interview (MINI-Plus) were obtained from 78 patients aged 60 and over to determine diagnosis, age at onset of the first affective episode, childhood abuse, family history of psychiatric disorders and past and recent stressful life events. Increased family history of psychiatric disorders was the only factor associated with an earlier age at onset of BD. Less family history of psychiatric disorders and more negative stressors were significantly associated with a later age at onset of the first (hypo)manic episode. Age at onset, history of childhood abuse, and past stressful life events were assessed retrospectively. Family members of BD patients were not interviewed. Our findings suggest that age at onset can define distinct BD phenotypes. More specifically there was a stronger heredity of BD and other psychiatric disorders in patients with an early age of onset of BD. Negative stressors may play a specific role in patients with a late age at onset of a first (hypo)manic episode. Copyright © 2015 Elsevier B.V. All rights reserved.

Pain in Neurodegenerative Disease: Current Knowledge and Future Perspectives

PubMed Central

de Tommaso, Marina; Arendt-Nielsen, Lars; Defrin, Ruth; Kunz, Miriam; Pickering, Gisele; Valeriani, Massimiliano

2016-01-01

Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD related disorders, motor neuron diseases (MND), Huntington's disease (HD), spinocerebellar ataxia (SCA), and spinal muscular atrophy (SMA), is mainly addressed to motor and cognitive impairment, with special care to vital functions as breathing and feeding. Many of these patients complain of painful symptoms though their origin is variable, and their presence is frequently not considered in the treatment guidelines, leaving their management to the decision of the clinicians alone. However, studies focusing on pain frequency in such disorders suggest a high prevalence of pain in selected populations from 38 to 75% in AD, 40% to 86% in PD, and 19 to 85% in MND. The methods of pain assessment vary between studies so the type of pain has been rarely reported. However, a prevalent nonneuropathic origin of pain emerged for MND and PD. In AD, no data on pain features are available. No controlled therapeutic trials and guidelines are currently available. Given the relevance of pain in neurodegenerative disorders, the comprehensive understanding of mechanisms and predisposing factors, the application and validation of specific scales, and new specific therapeutic trials are needed. PMID:27313396

ADAM10 as a therapeutic target for brain diseases: from developmental disorders to Alzheimer's disease.

PubMed

Marcello, Elena; Borroni, Barbara; Pelucchi, Silvia; Gardoni, Fabrizio; Di Luca, Monica

2017-11-01

In the central nervous system a disintegrin and metalloproteinase 10 (ADAM10) controls several functions such as neurodevelopment, synaptic plasticity and dendritic spine morphology thanks to its activity towards a high number of substrates, including the synaptic cell adhesion molecules as the Amyloid Precursor Protein, N-cadherin, Notch and Ephrins. In particular, ADAM10 plays a key role in the modulation of the molecular mechanisms responsible for dendritic spine formation, maturation and stabilization and in the regulation of the molecular organization of the glutamatergic synapse. Consequently, an alteration of ADAM10 activity is strictly correlated to the onset of different types of synaptopathies, ranging from neurodevelopmental disorders, i.e. autism spectrum disorders, to neurodegenerative diseases, i.e. Alzheimer's Disease. Areas covered: We describe the most recent discoveries in understanding of the role of ADAM10 activity at the glutamatergic excitatory synapse and its involvement in the onset of neurodevelopmental and neurodegenerative disorders. Expert opinion: A progress in the understanding of the molecular mechanisms driving ADAM10 activity at synapses and its alterations in brain disorders is the first step before designing a specific drug able to modulate ADAM10 activity.

[Pathology of basal ganglia in neurodegenerative diseases].

PubMed

Wakabayashi, Koichi; Tanji, Kunikazu; Mori, Fumiaki

2009-04-01

Intra- and/or extracellular proteinaceous inclusions in the brain tissue are characteristic pathological markers of many neurodegenerative diseases. Tau protein in neurofibrillary tangles and beta-amyloid in senile plaques are associated with Alzheimer's disease. Tau is associated with various neurological conditions, which are collectively referred to as tauopathies. Alpha-synucleinopathy is a term that collectively refers to a set of diseases in which neurodegeneration is accompanied by intracellular accumulation of alpha-synuclein in neurons or glial cells. Recently, TDP-43 has been identified as a major disease protein in the ubiquitinated inclusions in deseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration with tau-negative, ubiquitin-positive inclusions. Thus, these neurodegenerative disorders comprise a new disease class, namely, TDP-43 proteinopathy. In this article, we review the present understanding of histopathological features of basal ganglia lesions in protein conformation disorders, including tauopathy, alpha-synucleinopathy, and TDP-43 proteinopathy.

A Follow-up Study of Early Onset Psychosis: Comparison between Outcome Diagnoses of Schizophrenia, Mood Disorders, and Personality Disorders.

ERIC Educational Resources Information Center

McClellan, Jon M.; And Others

1993-01-01

This study of 95 youths previously diagnosed with psychotic disorders found that at follow-up, 24 had a diagnosis of schizophrenia, 9 with psychotic mood disorders, 5 with personality disorders, and 1 with schizo-affective disorder. The study confirmed findings regarding early onset schizophrenia and psychotic mood disorders and emphasized the…

Amino acids as dietary excitotoxins: a contribution to understanding neurodegenerative disorders.

PubMed

Meldrum, B

1993-01-01

The possibility that some acidic amino acids occurring naturally or as additives in the diet can act as excitotoxins producing central nervous system pathology has been the subject of extensive debate in the last 20 years and is here reviewed. High doses of glutamate, aspartate or related excitatory amino acids given in isolation to neonatal rodents produce acute degeneration organs. Neuropathology resulting from consumption of glutamate or aspartate has not been described in man. Various unusual amino acids of plant origin can produce acute excitotoxic syndromes. In man domoate (consumed in mussels that have fed on (Nitschia pungens) can produce an acute syndrome associated with limbic system lesions and anterograde amnesia. Kainate and domoate produce similar syndromes in rodents; acromelate produces spinal pathology. The mechanisms and manifestations of chronic excitotoxicity are less clearly established. A combination of impaired energy metabolism or impaired buffering of calcium and free radicals and endogenous or exogenous excitotoxins may contribute to neuronal loss in human neurodegenerative disorders.

Age-Related Sexual Dimorphism in Temporal Discrimination and in Adult-Onset Dystonia Suggests GABAergic Mechanisms.

PubMed

Butler, John S; Beiser, Ines M; Williams, Laura; McGovern, Eavan; Molloy, Fiona; Lynch, Tim; Healy, Dan G; Moore, Helena; Walsh, Richard; Reilly, Richard B; O'Riordan, Seán; Walsh, Cathal; Hutchinson, Michael

2015-01-01

Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants. We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients. We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of onset and (ii) an analysis of temporal discrimination thresholds in 220 unaffected first-degree relatives (125 women) of cervical dystonia patients. In 53 studies of dystonia phenotypes, the proportion of men showed a highly significant negative association with mean age of onset (p < 0.0001, pseudo-R (2) = 59.6%), with increasing female predominance from 40 years of age. Age of onset and phenotype together explained 92.8% of the variance in proportion of men. Temporal discrimination in relatives under the age of 35 years is faster in women than men but the age-related rate of deterioration in women is twice that of men; after 45 years of age, men have faster temporal discrimination than women. Temporal discrimination in unaffected relatives of cervical dystonia patients and sex ratios in adult-onset dystonia phenotypes show similar patterns of age-related sexual dimorphism. Such age-related sexual dimorphism in temporal discrimination and adult-onset focal dystonia may reflect common underlying mechanisms. Cerebral GABA levels have been reported to show similar age-related sexual dimorphism in healthy participants and may be the mechanism underlying the observed age-related sexual dimorphism in temporal discrimination and the sex ratios in AOIFD.

Omental transplantation for neurodegenerative diseases

PubMed Central

Rafael, Hernando

2014-01-01

Up to date, almost all researchers consider that there is still no effective therapy for neurodegenerative diseases (NDDs) and therefore, these diseases are incurable. However, since May 1998, we know that a progressive ischemia in the medial temporal lobes and subcommissural regions can cause Alzheimer’s disease; because, in contrast to this, its revascularization by means of omental tissue can cure or improve this disease. Likewise we observed that the aging process, Huntington’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis; all of them are of ischemic origin caused by cerebral atherosclerosis, associated with vascular anomalies and/or environmental chemicals. On the contrary, an omental transplantation on the affected zone can stop and improve these diseases. For these reasons, I believe that NDDs, are wrongly classified as neurodegenerative disorders. PMID:25232510

Multicentric prevalence study of anti P ribosomal autoantibodies in juvenile onset systemic lupus erythematosus compared with adult onset systemic lupus erythematosus.

PubMed

Pisoni, Cecilia N; Muñoz, Sebastián Andrés; Carrizo, Carolina; Cosatti, Micaela; Álvarez, Analía; Dubinsky, Diana; Bresan, Eleonora; Russo, Ricardo; Borgia, Ezequiel; García, Mercedes; Sansinanea, Pierina; Basta, María Cristina; D'Amico, Maria Agustina; Barreira, Juan Carlos; Lancioni, Eliana; Soriano, Enrique; Cunto, Carmen de; Beron, Ana; Eimon, Alicia

2015-01-01

To investigate the prevalence and associations with clinical manifestations of anti- P ribosomal antibodies in patients with juvenile-onset and adult-onset systemic lupus erythematosus (SLE). Clinical and serological data of 30 patients with juvenile-onset SLE (age at onset younger than 16 years old) were compared with data of 92 patients with adult-onset SLE. Symptoms occurring during the entire disease course were considered. Anti- P ribosomal antibodies were tested by ELISA. Anti- P ribosomal antibodies were found significantly more often in pediatric-onset SLE patients (26.7% vs. 6.5%; OR=5.21 [CI95%=1.6-16.5], p=0.003). Alopecia (OR=10.11, CI 95%=1.25-97) and skin rash (non discoid) (OR=4.1, CI 95%=1.25-13.89) were significantly associated with anti- P ribosomal antibodies. Anti-ribosomal P antibodies are more often found in patients with juvenile SLE. Alopecia and skin rash were the only clinical manifestations associated to anti-ribosomal P antibodies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study.

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Smith, Vanessa; Cutolo, Maurizio; Foeldvari, Ivan

2015-11-01

Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders.

PubMed

Goldman, S E; Alder, M L; Burgess, H J; Corbett, B A; Hundley, R; Wofford, D; Fawkes, D B; Wang, L; Laudenslager, M L; Malow, B A

2017-06-01

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.

Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders

PubMed Central

Goldman, SE; Alder, ML; Burgess, HJ; Corbett, BA; Hundley, R; Wofford, D; Fawkes, DB; Wang, L; Laudenslager, ML; Malow, BA

2017-01-01

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (four weeks), and salivary cortisol and melatonin (four days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors. PMID:28286917

Offspring of depressed and anxious patients: Help-seeking after first onset of a mood and/or anxiety disorder.