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Sample records for early-onset major depression

  1. Reports of the childhood home environment in early-onset dysthymia and episodic major depression.

    PubMed

    Lizardi, H; Klein, D N; Ouimette, P C; Riso, L P; Anderson, R L; Donaldson, S K

    1995-02-01

    This study addressed 2 questions: (a) is early-onset dysthymia associated with reports of a disturbed childhood home environment; and (b) can adverse early experiences account, at least in part, for the differing clinical presentations of dysthymia and major depression? Participants included 97 outpatients with early-onset dysthymia, 45 outpatients with episodic major depression, and 45 normal controls. The early home environment was assessed blind to diagnosis using both interview and self-report measures. Early-onset dysthymia patients reported significantly more physical and sexual abuse and poorer relationships with both parents than normal controls. In addition, patients with dysthymia reported having received significantly poorer parenting than those with episodic major depression. The results could not be accounted for by mood state effects, comorbidity with borderline and antisocial personality disorder, or comorbid major depression.

  2. Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course?

    PubMed

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

    2014-11-01

    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 single nucleotide polymorphism 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.

  3. Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

    ERIC Educational Resources Information Center

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

    2008-01-01

    Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

  4. Can lncRNAs be indicators for the diagnosis of early onset or acute schizophrenia and distinguish major depressive disorder and generalized anxiety disorder?-A cross validation analysis.

    PubMed

    Cui, Xuelian; Niu, Wei; Kong, Lingming; He, Mingjun; Jiang, Kunhong; Chen, Shengdong; Zhong, Aifang; Li, Wanshuai; Lu, Jim; Zhang, Liyi

    2017-03-28

    Depression and anxiety are apparent symptoms in the early onset or acute phase of schizophrenia (SZ), which complicate timely diagnosis and treatment. It is imperative to seek an indicator to distinguish schizophrenia from depressive and anxiety disorders. Using lncRNA microarray profiling and RT-PCR, three up-regulated lncRNAs in SZ, six down-regulated lncRNAs in major depressive disorder (MDD), and three up-regulated lncRNAs in generalized anxiety disorder (GAD) had been identified as potential biomarkers. All the lncRNAs were, then, cross-validated in 40 SZ patients, 40 MDD patients, 40 GAD patients, and 40 normal controls. Compared with controls, three up-regulated SZ lncRNAs had a significantly down-regulated expression in GAD, and no remarkable differences existed between MDD and the controls. Additionally, the six down-regulated MDD lncRNAs were expressed in an opposite fashion in SZ, and the expression of the three up-regulated GAD lncRNAs were significantly different between SZ and GAD. These results indicate that the expression patterns of the three up-regulated SZ lncRNAs could not be completely replicated in MDD and GAD, and vice versa. Thus, these three SZ lncRNAs seem to be established as potential indicators for diagnosis of schizophrenia and distinguishing it from MDD and GAD.© 2017 Wiley Periodicals, Inc.

  5. Major depression

    MedlinePlus

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  6. Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

    ERIC Educational Resources Information Center

    Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

    2016-01-01

    This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

  7. Reduced sleep spindle activity in early-onset and elevated risk for depression Running head: Sleep Spindles and Adolescent MDD

    PubMed Central

    Lopez, Jorge; Hoffmann, Robert; Armitage, Roseanne

    2010-01-01

    Objective Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than in adulthood, and as such, may be a more sensitive measure of sleep alteration than PSG in early-onset depression. This study investigated SPA changes related to early-onset MDD, comparing those already ill and those at high-risk for MDD to healthy non-depressed controls. Method The study included 63 participants (8-15 year-olds): 21 currently depressed, 21 at high-risk for MDD based on positive family history of MDD, and 21 healthy controls with no personal or family history of psychiatric illness. All participants maintained a regular sleep/wake schedule for 5 days, followed by 2 nights in the lab. SPA was analyzed in Stage 2 of non-Rapid Eye Movement (NREM) sleep. Results SPA differed significantly between groups, particularly in the late part of the night (F2,62=7.3 p=0.001). Although, the difference was greatest between MDD and healthy controls, both the MDD (p=0.0004) and at high-risk groups (p=0.02) had significantly lower SPA compared to healthy controls. SPA deficit was more prominent in females than males (F5,62=5.19 p=0.005). Conclusions Low SPA characterizes youths with MDD and those at high-risk, particularly among girls, suggesting that early-onset depression and risk for the illness are associated with decreased neuroplasticity. PMID:20732629

  8. Apathy and depressive mood in nursing home patients with early-onset dementia.

    PubMed

    Leontjevas, Ruslan; van Hooren, Susan; Waterink, Wim; Mulders, Ans

    2009-01-01

    The study explored whether apathy and depressive mood symptoms (DMS) are related to cognitive and functional features of dementia in 63 nursing home (NH) residents with early-onset dementia (EOD). All EOD residents from one NH (n = 41) and a random sample from another NH were assessed for depressive symptoms (Montgomery Asberg Depression Rating Scale [MADRS]), apathy (Neuropsychiatric Inventory [NPI]), global cognitive functions (Mini-Mental State Examination [MMSE]), activities of daily living (ADL, Minimum Data Set-Resident Assessment Instrument [MDS-RAI]), and overall dementia severity (Global Deterioration Scale [GDS]). DMS were not associated with apathy and dementia severity. Regression analyses adjusted for age, gender, the type of dementia, and DMS revealed that dementia severity measures accounted, respectively, for 14% (ADL), 13% (GDS), and 9% (MMSE) of the variance in apathy. In line with previous research in older patients, the higher apathy scores were associated with more cognitive and functional problems in EOD.

  9. An Observational Analysis of Behavior in Depressed Preschoolers: Further Validation of Early-Onset Depression

    ERIC Educational Resources Information Center

    Luby, Joan L.; Sullivan, Jill; Belden, Andy; Stalets, Melissa; Blankenship, Samantha; Spitznagel, Edward

    2006-01-01

    Objective: To investigate whether higher levels of negative and lower levels of positive behaviors could be observed in a sample of depressed preschoolers. Support for the validity of preschool depression is now available; however, objective evidence of negative behaviors among depressed preschoolers is needed. Method: A structured observational…

  10. Major depression.

    PubMed

    Bentley, Susan M; Pagalilauan, Genevieve L; Simpson, Scott A

    2014-09-01

    Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered.

  11. Reduced Sleep Spindle Activity in Early-Onset and Elevated Risk for Depression

    ERIC Educational Resources Information Center

    Lopez, Jorge; Hoffmann, Robert; Armitage, Roseanne

    2010-01-01

    Objective: Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than…

  12. 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…

  13. Depression (Major Depressive Disorder)

    MedlinePlus

    ... unrelated to the reason for your appointment Key personal information, including any major stresses or recent life ... accompanied by delusions or hallucinations, which may involve personal inadequacy or other negative themes Catatonia — depression that ...

  14. Depression (Major Depressive Disorder)

    MedlinePlus

    ... related. Depression can cause pain — and pain can cause depression. Sometimes pain and depression create a vicious cycle ... depression worsens feelings of pain. In many people, depression causes unexplained physical symptoms such as back pain or ...

  15. Emanuel Miller Lecture: Early Onset Depressions--Meanings, Mechanisms and Processes

    ERIC Educational Resources Information Center

    Goodyer, Ian M.

    2008-01-01

    Background: Depressive syndromes in children and adolescents constitute a serious group of mental disorders with considerable risk for recurrence. A more precise understanding of aetiology is necessary to improve treatment and management. Methods: Three neuroactive agents are purported to be involved in the aetiology of these disorders: serotonin,…

  16. The significant other history: an interpersonal-emotional history procedure used with the early-onset chronically depressed patient.

    PubMed

    McCullough, James P; Lord, Benjamin D; Martin, Aaron M; Conley, Kathryn A; Schramm, Elisabeth; Klein, Daniel N

    2011-01-01

    An interpersonal-emotional history procedure, the Significant Other History, is administered to the early-onset chronically depressed patient during the second therapy session in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). Patients are asked to name up to six significant others and answer two questions: (1) What was it like growing up with or being around this person? (2) What is the emotional "stamp" you take from this relationship that informs who you are today? An interpersonal-emotional theme reflecting the early learning history of the patient is derived from these "stamps" or causal theory conclusions. One transference hypothesis (TH) is derived from the Significant Other History (SOH) and is formulated in one sentence, such as "If I do this, then the therapist will likely do that" (e.g., "If I make a mistake around Dr. E, then Dr. E will label me 'stupid' or 'incompetent"). The transference hypothesis highlights the interpersonal content that most likely informs the patient's expectancy of the therapist's reactions toward him or her. Throughout the therapy process, the therapist will proactively employ the transference hypothesis in a technique known as the Interpersonal Discrimination Exercise to help patients cognitively and emotionally discriminate the practitioner from hurtful significant others. The goal here is to increase the patient's felt safety within the therapeutic dyad and eventually to generalize the felt safety to the patient's other relationships.

  17. Neurodegenerative evidences during early onset of depression in CMS rats as detected by proton magnetic resonance spectroscopy at 7 T.

    PubMed

    Hemanth Kumar, B S; Mishra, Sushanta Kumar; Rana, Poonam; Singh, Sadhana; Khushu, Subash

    2012-06-15

    Depression is a complex psychiatric disorder characterized by anhedonia and feeling of sadness and chronic mild stress (CMS) seems to be a valuable animal model of depression. CMS animal model was induced and validated using behavioral studies. In the present study we investigated the neuro-metabolite changes occurring in prefrontal cortex and hippocampus during the onset of depression, in CMS rat model using in vivo proton magnetic resonance spectroscopy ((1)H MRS) at field strength of 7 T. Results showed that CMS caused depression-like behavior in rats, as indicated by the decrease in sucrose consumption and locomotor activity. (1)H MRS was performed in both control and CMS rats (n=10, in each group) and the quantitative assessment of the neurometabolites was done using LC model. Relative concentrations of all the metabolites along with the macromolecules were calculated for analysis. The results revealed a significant decrease of glutamate (Glu), glutamine (Gln), NAA+NAAG, Glx and GABA levels in both hippocampus and prefrontal cortex of CMS animals and an elevated level of myo-ionisitol (mI) and taurine (Tau) was observed only in hippocampus. These metabolite fluctuations revealed by proton MRS indicate that there might be change in the neuronal integrity of the glial cells and neurons within prefrontal cortex and hippocampus in CMS model of depression. The present study also suggests that there may be a degenerative process concerning the brain morphology in the CMS rats. The overall finding using (1)H MRS suggests that, there might be a major role of the glia and neuron in the onset of depression.

  18. Major Depression Among Adults

    MedlinePlus

    ... on NIMH’s depression page . NEXT Statistical Methods and Measurement Caveats Diagnostic Assessment: Modules related to major depressive ... apartments, condominiums; civilians living in housing on military bases, etc.) and persons in non-institutional group quarters ( ...

  19. Early onset pauciarticular arthritis is the major risk factor for naproxen-induced pseudoporphyria in juvenile idiopathic arthritis

    PubMed Central

    Schäd, Susanne G; Kraus, Andrea; Haubitz, Imme; Trcka, Jiri; Hamm, Henning; Girschick, Hermann J

    2007-01-01

    Pseudoporphyria (PP) is characterized by skin fragility, blistering and scarring in sun-exposed skin areas without abnormalities in porphyrin metabolism. The phenylpropionic acid derivative group of nonsteroidal anti-inflammatory drugs, especially naproxen, is known to cause PP. Naproxen is currently one of the most prescribed drugs in the therapy of juvenile idiopathic arthritis (JIA). The prevalence of PP was determined in a 9-year retrospective study of children with JIA and associated diseases. In addition, we prospectively studied the incidence of PP in 196 patients (127 girls and 69 boys) with JIA and associated diseases treated with naproxen from July 2001 to March 2002. We compared these data with those from a matched control group with JIA and associated diseases not treated with naproxen in order to identify risk factors for development of PP. The incidence of PP in the group of children taking naproxen was 11.4%. PP was particularly frequent in children with the early-onset pauciarticular subtype of JIA (mean age 4.5 years). PP was associated with signs of disease activity, such as reduced haemoglobin (<11.75 g/dl), and increased leucocyte counts (>10,400/μl) and erythocyte sedimentation rate (>26 mm/hour). Comedications, especially chloroquine intake, appeared to be additional risk factors. The mean duration of naproxen therapy before the onset of PP was 18.1 months, and most children with PP developed their lesions within the first 2 years of naproxen treatment. JIA disease activity seems to be a confounding factor for PP. In particular, patients with early-onset pauciarticular JIA patients who have significant inflammation appear to be prone to developing PP upon treatment with naproxen. PMID:17266758

  20. Physical mapping of the major early-onset familial Alzheimer`s disease locus on chromosome 14 and analysis of candidate gene sequences

    SciTech Connect

    Tanzi, R.E.; Romano, D.M.; Crowley, A.C.

    1994-09-01

    Genetic studies of kindreds displaying evidence for familial AD (FAD) have led to the localization of gene defects responsible for this disorder on chromosomes 14, 19, and 21. A minor early-onset FAD gene on chromosome 21 has been identified to enode the amyloid precursor protein (APP), and the late-onset FAD susceptibility locus on chromosome 19 has been shown to be in linkage disequilibrium with the E4 allele of the APOE gene. Meanwhile, the locus responsible for the major form of early-onset FAD on chromosome 14q24 has not yet been identified. By recombinational analysis, we have refined the minimal candidate region containing the gene defect to approximately 3 megabases in 14q24. We will describe our laboratory`s progress on attempts to finely localize this locus, as well as test known candidate genes from this region for either inclusion in the minimal candidate region or the presence of pathogenic mutations. Candidate genes that have been tested so far include cFOS, heat shock protein 70 member (HSF2A), transforming growth factor beta (TGFB3), the trifunctional protein C1-THF synthase (MTHFD), bradykinin receptor (BR), and the E2k component of a-ketoglutarate dehydrogenase. HSP2A, E2k, MTHFD, and BR do not map to the current defined minimal candidate region; however, sequence analysis must be performed to confirm exclusion of these genes as true candidates. Meanwhile, no pathogenic mutations have yet been found in cFOS or TGFB3. We have also isolated a large number of novel transcribed sequences from the minimal candidate region in the form of {open_quotes}trapped exons{close_quotes} from cosmids identified by hybridization to select YAC clones; we are currently in the process of searching for pathogenic mutations in these exons in affected individuals from FAD families.

  1. Do You Have Major Depression?

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Depression Do You Have Major Depression? Past Issues / Fall 2009 Table of Contents Simple ... member may have major depression. —NIMH Types of Depression Just like other illnesses, such as heart disease, ...

  2. Major depression, dysthymia and depressive personality disorder.

    PubMed

    Hirschfeld, R M

    1994-12-01

    The separation of persistent depression into meaningful and useful subcategories, including major depression, dysthymia, recurrent brief depression, and depressive personality disorder, is the subject of much debate. Depressions can be grouped on the basis of their type and severity of symptoms, aetiology, clinical course, or their association with other psychiatric illnesses. Several investigators have conducted epidemiologic and family studies to evaluate the prevalence of depressive disorders, their diagnostic stability over time, and the amount of overlap among the disorders. Although progress has been made toward a better understanding of the different disorders, insufficient evidence exists to support the hypothesis that these disorders are separate and distinct from one another. However, preliminary data suggest that depressive personality disorder is separate from the other disorders. Additionally, several questions have been raised, particularly the extent to which differentiation between the depressive disorders, specifically major depression and dysthymia, has an impact on treatment decisions.

  3. Major depression with psychotic features

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000933.htm Major depression with psychotic features To use the sharing features on this page, please enable JavaScript. Major depression with psychotic features is a mental disorder in ...

  4. Major depression: emerging therapeutics.

    PubMed

    Sen, Srijan; Sanacora, Gerard

    2008-01-01

    The first effective antidepressants, monoamine oxidase inhibitors and tricyclic antidepressants, were identified 50 years ago, largely through serendipity. These medications were found to improve mood in a little more than half of depressed patients after a few weeks of chronic use. Almost all antidepressants prescribed today were developed through minor modifications of these original antidepressants and, like monoamine oxidase inhibitors and tricyclic antidepressants, act primarily through monoaminergic mechanisms. Although there have been improvements in side-effect profiles and overdose toxicity, these newer medications have not provided substantial advances in the efficacy and speed of the antidepressant effect for patients. Over the last 2 decades, our understanding of the neurobiology underlying depression has expanded exponentially. Given this expansion, we may be nearing an inflection point in antidepressant drug development, at which useful medicines will be designed through a rational understanding of the biological systems. In this review, we discuss the biological basis and preclinical and clinical evidence for a series of promising classes of antidepressants developed primarily out of a pathophysiologically informed approach.

  5. Premenstrual depression predicts future major depressive disorder.

    PubMed

    Graze, K K; Nee, J; Endicott, J

    1990-02-01

    To assess the power of premenstrual changes as a risk factor for future major depressive disorder (MDD), we conducted a follow-up study of 36 women who had volunteered for menstrual cycle studies. Scores on the depressive subscale of the Premenstrual Assessment Form (PAF) at initial evaluation were found to be significantly correlated (r = 0.35) with the occurrence of MDD during the follow-up period. Moreover, multiple regression analysis indicated that the PAF scores had predictive value above and beyond 2 known risk factors for MDD, family history of depression and prior personal history of depression. The Premenstrual Change Index, a score derived from prospective daily self-ratings of severity of dysphoric symptoms, was also correlated with interval MDD, but did not enhance the predictive power of the PAF score. We conclude that the assessment of premenstrual depression has validity in identifying women at risk for future MDD, even when a retrospective instrument, PAF, is utilized for such assessment.

  6. Discovering endophenotypes for major depression.

    PubMed

    Hasler, Gregor; Drevets, Wayne C; Manji, Husseini K; Charney, Dennis S

    2004-10-01

    The limited success of genetic studies of major depression has raised questions concerning the definition of genetically relevant phenotypes. This paper presents strategies to improve the phenotypic definition of major depression by proposing endophenotypes at two levels: First, dissecting the depressive phenotype into key components results in narrow definitions of putative psychopathological endophenotypes: mood bias toward negative emotions, impaired reward function, impaired learning and memory, neurovegetative signs, impaired diurnal variation, impaired executive cognitive function, psychomotor change, and increased stress sensitivity. A review of the recent literature on neurobiological and genetic findings associated with these components is given. Second, the most consistent heritable biological markers of major depression are proposed as biological endophenotypes for genetic studies: REM sleep abnormalities, functional and structural brain abnormalities, dysfunctions in serotonergic, catecholaminergic, hypothalamic-pituitary-adrenocortical axis, and CRH systems, and intracellular signal transduction endophenotypes. The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiality, and clinical and biological plausibility. Finally, the case is made for the development of a new classification system in order to reduce the heterogeneity of depression representing a major impediment to elucidating the genetic and neurobiological basis of this common, severe, and often life-threatening illness.

  7. Major Depression Can Be Prevented

    ERIC Educational Resources Information Center

    Munoz, Ricardo F.; Beardslee, William R.; Leykin, Yan

    2012-01-01

    The 2009 Institute of Medicine report on prevention of mental, emotional, and behavioral disorders (National Research Council & Institute of Medicine, 2009b) presented evidence that major depression can be prevented. In this article, we highlight the implications of the report for public policy and research. Randomized controlled trials have shown…

  8. Molecular signatures of major depression.

    PubMed

    Cai, Na; Chang, Simon; Li, Yihan; Li, Qibin; Hu, Jingchu; Liang, Jieqin; Song, Li; Kretzschmar, Warren; Gan, Xiangchao; Nicod, Jerome; Rivera, Margarita; Deng, Hong; Du, Bo; Li, Keqing; Sang, Wenhu; Gao, Jingfang; Gao, Shugui; Ha, Baowei; Ho, Hung-Yao; Hu, Chunmei; Hu, Jian; Hu, Zhenfei; Huang, Guoping; Jiang, Guoqing; Jiang, Tao; Jin, Wei; Li, Gongying; Li, Kan; Li, Yi; Li, Yingrui; Li, Youhui; Lin, Yu-Ting; Liu, Lanfen; Liu, Tiebang; Liu, Ying; Liu, Yuan; Lu, Yao; Lv, Luxian; Meng, Huaqing; Qian, Puyi; Sang, Hong; Shen, Jianhua; Shi, Jianguo; Sun, Jing; Tao, Ming; Wang, Gang; Wang, Guangbiao; Wang, Jian; Wang, Linmao; Wang, Xueyi; Wang, Xumei; Yang, Huanming; Yang, Lijun; Yin, Ye; Zhang, Jinbei; Zhang, Kerang; Sun, Ning; Zhang, Wei; Zhang, Xiuqing; Zhang, Zhen; Zhong, Hui; Breen, Gerome; Wang, Jun; Marchini, Jonathan; Chen, Yiping; Xu, Qi; Xu, Xun; Mott, Richard; Huang, Guo-Jen; Kendler, Kenneth; Flint, Jonathan

    2015-05-04

    Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual's somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 × 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

  9. Molecular Signatures of Major Depression

    PubMed Central

    Cai, Na; Chang, Simon; Li, Yihan; Li, Qibin; Hu, Jingchu; Liang, Jieqin; Song, Li; Kretzschmar, Warren; Gan, Xiangchao; Nicod, Jerome; Rivera, Margarita; Deng, Hong; Du, Bo; Li, Keqing; Sang, Wenhu; Gao, Jingfang; Gao, Shugui; Ha, Baowei; Ho, Hung-Yao; Hu, Chunmei; Hu, Jian; Hu, Zhenfei; Huang, Guoping; Jiang, Guoqing; Jiang, Tao; Jin, Wei; Li, Gongying; Li, Kan; Li, Yi; Li, Yingrui; Li, Youhui; Lin, Yu-Ting; Liu, Lanfen; Liu, Tiebang; Liu, Ying; Liu, Yuan; Lu, Yao; Lv, Luxian; Meng, Huaqing; Qian, Puyi; Sang, Hong; Shen, Jianhua; Shi, Jianguo; Sun, Jing; Tao, Ming; Wang, Gang; Wang, Guangbiao; Wang, Jian; Wang, Linmao; Wang, Xueyi; Wang, Xumei; Yang, Huanming; Yang, Lijun; Yin, Ye; Zhang, Jinbei; Zhang, Kerang; Sun, Ning; Zhang, Wei; Zhang, Xiuqing; Zhang, Zhen; Zhong, Hui; Breen, Gerome; Wang, Jun; Marchini, Jonathan; Chen, Yiping; Xu, Qi; Xu, Xun; Mott, Richard; Huang, Guo-Jen; Kendler, Kenneth; Flint, Jonathan

    2015-01-01

    Summary Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease. PMID:25913401

  10. Neurobiology of major depressive disorder.

    PubMed

    Villanueva, Rosa

    2013-01-01

    We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed.

  11. Recurrence in Major Depression: A Conceptual Analysis

    ERIC Educational Resources Information Center

    Monroe, Scott M.; Harkness, Kate L.

    2011-01-01

    Theory and research on major depression have increasingly assumed a recurrent and chronic disease model. Yet not all people who become depressed suffer recurrences, suggesting that depression is also an acute, time-limited condition. However, few if any risk indicators are available to forecast which of the initially depressed will or will not…

  12. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

    PubMed

    Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

    2015-11-10

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

  13. Symptoms of Major Depression and Complicated Grief

    MedlinePlus

    ... Loss of a Loved One Symptoms of major depression and complicated grief Depression It’s common for people to have sadness, pain, ... might be getting worse—going into a major depression. About 1 in 5 bereaved people will develop ...

  14. Molecular epidemiology of major depressive disorder.

    PubMed

    Kiyohara, Chikako; Yoshimasu, Kouichi

    2009-03-01

    Major depressive disorder causes significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, major depressive disorder increases the risk of suicidal ideation, attempted suicide and death by completed suicide. There is evidence that chronic stress can cause major depressive disorder. As for genetic factors, only minor susceptibility genes have been reliably identified. The serotonin system provides a logical source of susceptibility genes for depression, because this system is the target of selective serotonin reuptake-inhibitor drugs that are effective in treating depression. The 5-hydroxytryptamine (serotonin) transporter (5-HTT) has received particular attention because it is involved in the reuptake of serotonin at brain synapses. One common polymorphic variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which affects the promoter of the 5-HTT gene, causes reduced uptake of the neurotransmitter serotonin into the presynaptic cells in the brain. The authors discussed the relationship between genetic polymorphisms and major depressive disorder, with special emphasis on the 5-HTTTLPR polymorphism. As the 5-HTTLPR polymorphism was significantly associated with an increased risk of major depressive disorder, the 5-HTT gene may be a candidate for a major depressive disorder susceptibility gene. As major depressive disorder is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for major depressive disorder. Hopefully, in the future we will be able to screen for major depressive disorder susceptibility by using specific biomarkers.

  15. Major depressive disorder subtypes to predict long-term course

    PubMed Central

    van Loo, Hanna M.; Cai, Tianxi; Gruber, Michael J.; Li, Junlong; de Jonge, Peter; Petukhova, Maria; Rose, Sherri; Sampson, Nancy A.; Schoevers, Robert A.; Wardenaar, Klaas J.; Wilcox, Marsha A.; Al-Hamzawi, Ali Obaid; Andrade, Laura Helena; Bromet, Evelyn J.; Bunting, Brendan; Fayyad, John; Florescu, Silvia E.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Levinson, Daphna; Medina-Mora, Maria Elena; Nakane, Yoshibumi; Posada-Villa, Jose; Scott, Kate M.; Xavier, Miguel; Zarkov, Zahari; Kessler, Ronald C.

    2016-01-01

    Background Variation in course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. Methods Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs) followed by k-means cluster analysis, are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) Surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode; number of with an episode lasting most of the year) and severity (hospitalization for MDD; disability due to MDD). Results Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity and was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. Conclusions Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data. PMID:24425049

  16. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  17. 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.

  18. Emerging antidepressants to treat major depressive disorder.

    PubMed

    Block, Samantha G; Nemeroff, Charles B

    2014-12-01

    Depression is a common disorder with an annual risk of a depressive episode in the United States of 6.6%. Only 30-40% of patients remit with antidepressant monotherapy, leaving 60-70% of patients who do not optimally respond to therapy. Unremitted depressive patients are at increased risk for suicide. Considering the prevalence of treatment resistant depression and its consequences, treatment optimization is imperative. This review summarizes the latest treatment modalities for major depressive disorder including pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation and psychotherapy. Through advancements in research to better understand the pathophysiology of depression, advances in treatment will be realized.

  19. Early onset torsion dystonia (Oppenheim's dystonia)

    PubMed Central

    Kamm, Christoph

    2006-01-01

    Early onset torsion dystonia (EOTD) is a rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body. A US study estimated the prevalence at approximately 1 in 30,000. The estimated prevalence in the general population of Europe seems to be lower, ranging from 1 in 330,000 to 1 in 200,000, although precise numbers are currently not available. The estimated prevalence in the Ashkenazi Jewish population is approximately five to ten times higher, due to a founder mutation. Symptoms of EOTD typically develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. Distribution and severity of symptoms vary widely between affected individuals. The majority of cases from various ethnic groups are caused by an autosomal dominantly inherited deletion of 3 bp (GAG) in the DYT1 gene on chromosome 9q34. This gene encodes a protein named torsinA, which is presumed to act as a chaperone protein associated with the endoplasmic reticulum and the nuclear envelope. It may interact with the dopamine transporter and participate in intracellular trafficking, although its precise function within the cell remains to be determined. Molecular genetic diagnostic and genetic counseling is recommended for individuals with age of onset below 26 years, and may also be considered in those with onset after 26 years having a relative with typical early onset dystonia. Treatment options include botulinum toxin injections for focal symptoms, pharmacological therapy such as anticholinergics (most commonly trihexiphenydil) for generalized dystonia and surgical approaches such as deep brain stimulation of the internal globus pallidus or intrathecal baclofen application in severe cases. All patients have normal cognitive function, and despite a high rate of generalization of dystonia, 75% of those patients

  20. Major depressive episodes and diet pills.

    PubMed

    Patten, Scott B

    2002-10-01

    A variety of medications used to assist with weight loss have been implicated in the precipitation or induction of depressive symptoms and disorders. This is true of a large number of phenylethylamine agents possessing psychostimulant properties, non-phenylethylamine psychostimulants (e.g., caffeine) and the serotonergic agent, fenfluramine. There is, as yet, no substantial evidence linking the more modern weight loss drugs, sibutramine and orlistat, to the aetiology of major depression. Nevertheless, when these drugs are used, major depression will continue to be an important clinical consideration because of the elevated frequency with which major depression occurs in obese patients, the contribution that major depression may make to poor outcomes in non-pharmacological weight loss treatment and because of the interplay between symptoms of depression and weight loss treatment.

  1. DEXAMETHASONE SUPPRESSION TEST FOR MAJOR DEPRESSION

    PubMed Central

    Ghulam, R.; Anand, Mohini; Lal, Narottam; Trivedi, J.K.

    1985-01-01

    SUMMARY Overnight post dexamethasone plasma Cortisol levels were estimated in thirty patients of major depression and 30 controls. The cut-off point after which post dexamethasone plasma Cortisol level could be considered abnormal, in patients of major depression, has been worked out at 15 μg/dl in the present study. The results are discussed. PMID:21927130

  2. Delayed mood transitions in major depressive disorder.

    PubMed

    Korf, Jakob

    2014-05-01

    The hypothesis defended here is that the process of mood-normalizing transitions fails in a significant proportion of patients suffering from major depressive disorder. Such a failure is largely unrelated to the psychological content. Evidence for the hypothesis is provided by the highly variable and unpredictable time-courses of the depressive episodes. The main supporting observations are: (1) mood transitions within minutes or days have been reported during deep brain stimulation, naps after sleep deprivation and bipolar mood disorders; (2) sleep deprivation, electroconvulsive treatment and experimental drugs (e.g., ketamine) may facilitate mood transitions in major depressive disorder within hours or a few days; (3) epidemiological and clinical studies show that the time-to-recovery from major depressive disorder can be described with decay models implying very short depressive episodes; (4) lack of relationship between the length of depression and recovery episodes in recurrent depression; (5) mood fluctuations predict later therapeutic success in major depressive disorder. We discuss some recent models aimed to describe random mood transitions. The observations together suggest that the mood transitions have a wide variety of apparently unrelated causes. We suggest that the mechanism of mood transition is compromised in major depressive disorder, which has to be recognized in diagnostic systems.

  3. Atypical major depressive episode as initial presentation of intracranial germinoma in a male adolescent

    PubMed Central

    Chen, Yi-Ting; Su, Kuan-Pin; Chang, Jane Pei-Chen

    2017-01-01

    A 17-year-old adolescent boy presented with atypical major depressive episode (MDE) without specific focal neurological signs for 6 months. He had a diagnosis of intra-cranial germinoma, and the atypical MDE symptoms subsided after the operation. However, he had a relapse of atypical MDE 7 months after the first surgery. His mood and binge eating symptoms subsided, but intractable body weight gain only partially improved after treatment. When encountering manifestations of depression with atypical features, especially with binge eating symptoms in male children and adolescents, with early onset age, no family history, and prolonged depressive episodes, clinicians should consider not only mood disorders including bipolar spectrum disorders but also organic brain lesions such as intracranial germinoma. PMID:28053535

  4. Genetics Home Reference: early-onset glaucoma

    MedlinePlus

    ... of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. ... pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends ...

  5. Hippocampal atrophy in recurrent major depression.

    PubMed Central

    Sheline, Y I; Wang, P W; Gado, M H; Csernansky, J G; Vannier, M W

    1996-01-01

    Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity. Images Fig. 1 Fig. 4 PMID:8632988

  6. Examining Minor and Major Depression in Adolescents

    ERIC Educational Resources Information Center

    Gonzalez-Tejera, Gloria; Canino, Glorisa; Ramirez, Rafael; Chavez, Ligia; Shrout, Patrick; Bird, Hector; Bravo, Milagros; Martinez-Taboas, Alfonso; Ribera, Julio; Bauermeister, Jose

    2005-01-01

    Background: Research has shown that a large proportion of adolescents with symptoms of depression and substantial distress or impairment fail to meet the diagnostic criteria for a major depressive disorder (MDD). However, many of these undiagnosed adolescents may meet criteria for a residual category of the "Diagnostic and Statistical Manual of…

  7. Depression and major depressive disorder in patients with Parkinson's disease.

    PubMed

    Inoue, Takeshi; Kitagawa, Mayumi; Tanaka, Teruaki; Nakagawa, Shin; Koyama, Tsukasa

    2010-01-15

    The prevalence of depression in Parkinson's disease (PD) varies greatly. In this study, we investigated major depressive disorder (MDD) and depressive symptoms without MDD in patients with PD. The psychopathological characteristics of depressive symptoms were assessed by a psychiatric interview. A total of 105 Japanese patients with PD without dementia were included. The Japanese version of the Beck Depression Inventory-II (BDI-II) with a cutoff score of 13/14 was used to screen for depression. Using a structured interview, a comprehensive psychiatric evaluation of patients with BDI-II scores >13 (high BDI patients) was completed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR. Forty patients (38%) had a BDI-II >13, but 29 did not show any depressed mood. Five cases met the criteria for MDD (three current, two past) and one patient was diagnosed with minor depressive disorder. A slight depressed mood that was associated with worrying about PD was seen in 6 of 34 patients without any depressive disorder and fluctuated with aggravation of PD symptoms in two of these patients. For the diagnosis of MDD, the number of positive items from the DSM-IV-TR definition of MDD is most important and useful for differentiating MDD and non-MDD. The low-prevalence rate of MDD in our patient population suggests that PD may be a psychological stressor for MDD, but does not necessarily induce MDD.

  8. Emerging from Depression: Treatment of Adolescent Depression Using the Major Treatment Models of Adult Depression.

    ERIC Educational Resources Information Center

    Long, Kathleen M.

    Noting that adolescents who commit suicide are often clinically depressed, this paper examines various approaches in the treatment of depression. Major treatment models of adult depression, which can be directly applied to the treatment of the depressed adolescent, are described. Major treatment models and selected research studies are reviewed in…

  9. [Major depression: features indicative of bipolarity?].

    PubMed

    Azorin, J-M

    2011-12-01

    Several recent studies have shown that bipolar disorder is underdiagnosed in patients with major depression. Missing the diagnosis of a bipolar disorder may have serious and even occasionally fatal consequences for a patient with the disease. Moreover misdiagnosis may lead to inappropriate treatment and therefore contribute to worsening medical and functional prognosis. Although there are no pathognomonic characteristics of bipolar depression compared to unipolar depression, evidence-based findings suggest that some features may be indicative of bipolarity, in patients with depression. These features are related to clinical picture of depressive state, course of episode and illness, response to treatment, family history, comorbid conditions, as well as demographic and temperamental characteristics. Based on such features, some authors have proposed operationalized criteria or a diagnostic specific for bipolarity, to identify bipolar depression. Screening instruments may also be used, to facilitate early recognition. Validation studies of these diagnostic features and instruments are underway.

  10. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2014-04-01

    Mayeux RP, Alzheimer’s Disease Genetics Consortium. Whole-exome sequencing of Hispanic early-onset Alzheimer disease families identifies rare variants...majority of genetic risk for this form of Alzheimer disease unexplained. We performed Whole-Exome Sequencing (WES) on 55 individuals in 19 Caribbean...EOAD and ~11% of EOAD overall, leaving the majority of genetic risk for the most severe form of Alzheimer disease unexplained. Methods We

  11. [Vortioxetine in the treatment of major depression].

    PubMed

    de Bartolomeis, Andrea; Fagiolini, Andrea; Maina, Giuseppe

    2016-01-01

    Notwithstanding the high prevalence, functional burden, negative consequences and risk of chronicity of major depressive disorder, few innovative medications have been developed in recent years for the treatment of this heterogeneous disease. Vortioxetine is a multi-modal antidepressant that functions both as serotonin transporter (SERT) inhibitor and as 5-HT3, 5-HT7 and 5-HT1D receptors antagonist, 5-HT1A receptor agonist and 5-HT1B receptor partial agonist. A recent meta-analysis of 11 randomized, double-blind, placebo controlled, acute (6-8 weeks) treatment studies has demonstrated the efficacy of vortioxetine 5-20 mg/day in the treatment of depression, with an increasing effect associated with increasing dose. Additionally, vortioxetine 5-20 mg/day has shown efficacy on the whole range of depression symptoms (as demonstrated by the improvement of all single-item MADRS scores). Vortioxetine has also been shown effective in the treatment of severe depression and depression with inadequate response to a previous SSRI or SNRI treatment, as well as in the prevention of relapse. In studies designed to assess cognition in depression, vortioxetine showed evidence of improving cognitive performance in patients with acute major depressive disorder. Vortioxetine appears well-tolerated, with very limited effects on weight gain and sexual functioning. The most commonly occurring adverse event (nausea) was generally transitory.

  12. Interpersonal psychotherapy (IPT) in major depressive disorder.

    PubMed

    Brakemeier, Eva-Lotta; Frase, Lukas

    2012-11-01

    In this article, we will introduce interpersonal psychotherapy as an effective short-term treatment strategy in major depression. In IPT, a reciprocal relationship between interpersonal problems and depressive symptoms is regarded as important in the onset and as a maintaining factor of depressive disorders. Therefore, interpersonal problems are the main therapeutic targets of this approach. Four interpersonal problem areas are defined, which include interpersonal role disputes, role transitions, complicated bereavement, and interpersonal deficits. Patients are helped to break the interactions between depressive symptoms and their individual interpersonal difficulties. The goals are to achieve a reduction in depressive symptoms and an improvement in interpersonal functioning through improved communication, expression of affect, and proactive engagement with the current interpersonal network. The efficacy of this focused and structured psychotherapy in the treatment of acute unipolar major depressive disorder is summarized. This article outlines the background of interpersonal psychotherapy, the process of therapy, efficacy, and the expansion of the evidence base to different subgroups of depressed patients.

  13. Paroxetine treatment of major depressive disorder.

    PubMed

    Keller, Martin B

    2003-01-01

    Major depression is recognized as a common, often chronic and recurrent illness that is associated with significant disability and comorbidity. The treatment of patients with major depressive disorder has advanced tremendously in the past decade as a result of the availability of effective and well-tolerated antidepressants. Paroxetine is a widely studied selective serotonin reuptake inhibitor (SSRI) with evidence for efficacy and safety that is supported by a large body of published literature. Evidence for the efficacy and tolerability of anew controlled-release formulation of paroxetine also has been published. Findings from paroxetine clinical studies have added considerably to our knowledge and understanding of the treatment of major depressive disorder, particularly with regard to duration of treatment, the need for treating to full remission and with full doses, and treatment of patients with concurrent symptoms of anxiety.

  14. Treatment of resistant insomnia and major depression.

    PubMed

    Vellante, F; Cornelio, M; Acciavatti, T; Cinosi, E; Marini, S; Dezi, S; De Risio, L; Di Iorio, G; Martinotti, G; Di Giannantonio, M

    2013-01-01

    Daily rhythms regulate everiday life and sleep/wake alternation is the best expression of this. Disruptions in biological rhythms is strongly associated with mood disorders, often being the major feature of this, major depressive disorder first of all. Although stabilization of rhythms produced by treatments have important outcome on therapeutic efficacy, insomnia often remains an unresolved symptom when major depression has otherwise been successfully treated with antidepressant. We review scientific literature in order to better clarify how to better approach insomnia as a clinical aspect to investigate and to early treat while treating other psychiatric conditions, major depression in particular. Insomnia is associated with impaired quality of life. It can be resolved with adequate diagnosis and treatment: it should be considered a comorbid condition and should be early identificated and treated in a multidisciplinary way, so that the ideal of treatment for patients with treatment resistant insomnia in major depression is an integration of non-pharmacologic measures, along with judicious use of medication, often used as an adjunctive therapy.

  15. Major depressive disorder: reification and (maybe) rheostasis.

    PubMed

    Patten, S B

    2015-12-01

    The heterogeneity of clinical syndromes subsumed by diagnostic criteria for major depressive disorder (MDD) is regarded by some as a reason to abandon or modify the criteria. However, heterogeneity may be unavoidable because of the biopsychosocial complexity of depression. MDD may be characterised by complexities that cannot be distilled down to any brief set of diagnostic criteria. Psychiatrists and psychiatric epidemiologists may need to revise their expectations of this diagnosis in order to avoid over-estimating its ability to guide the selection of treatments and prediction of prognosis. An opposing perspective is that of reification, in which the diagnosis is viewed as being more real than it really is. The concept of rheostasis may help to explain some features of this condition, such as why major depressive episodes sometimes seem understandable or even adaptive (e.g. in the context of bereavement) whereas at other times such episodes are inexplicable and maladaptive.

  16. [Cognition - the core of major depressive disorder].

    PubMed

    Polosan, M; Lemogne, C; Jardri, R; Fossati, P

    2016-02-01

    Cognitive deficits have been only recently recognized as a major phenotype determinant of major depressive disorder, although they are an integral part of the definition of the depressive state. Congruent evidence suggest that these cognitive deficits persist beyond the acute phase and may be identified at all ages. The aim of the current study was to review the main meta-analyses on cognition and depression, which encompasses a large range of cognitive domains. Therefore, we discuss the "cold" (attention, memory, executive functions) and "hot" (emotional bias) cognitive impairments in MDD, as well as those of social cognition domains (empathy, theory of mind). Several factors interfere with cognition in MDD such as clinical (melancholic, psychotic...) features, age, age of onset, illness severity, medication and comorbid condition. As still debated in the literature, the type of relationship between the severity of cognitive symptoms and functioning in depression is detailed, thus highlighting their predictive value of functional outcome, independently of the affective symptoms. A better identification of the cognitive deficits in MDD and a monitoring of the effects of different treatments require appropriate instruments, which may be developed by taking advantage of the increasing success of computing tools. Overall, current data suggest a core role for different cognitive deficits in MDD, therefore opening new perspectives for optimizing the treatment of depression.

  17. Risk assessment in neonatal early onset sepsis.

    PubMed

    Mukhopadhyay, Sagori; Puopolo, Karen M

    2012-12-01

    The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures.

  18. [Brain imaging in early onset anorexia].

    PubMed

    Bargiacchi, A

    2014-05-01

    Structural and functional brain alterations in the structures involved in taste processing, emotions regulation and the reward system have been described in anorexia nervosa. The neurodevelopmental origin of this disorder has been recently discussed. In this article, brain-imaging data in early onset anorexia nervosa will be recalled and the relationship between clinical symptoms, normal brain maturation and brain imaging data in adolescents and adults will be discussed.

  19. Vortioxetine for the treatment of major depression.

    PubMed

    Dhir, A

    2013-12-01

    Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders. Vortioxetine has a unique "multi-modal" mechanism of action. It inhibits the activity of serotonin transporters and is an agonist of serotonin 5-HT1A receptor, partial agonist of 5-HT1B and antagonist of 5-HT3A, 5-HT7 and 5-HT1D receptors. Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. Vortioxetine reverses cognitive decline in patients with depression making it a unique molecule. The molecule lacks any serious side effects and drug-drug interactions. However, dose adjustments are required if vortioxetine is co-administered with rifampicin or bupropion. The molecule is under review by various regulatory agencies around the world for the treatment of major depression.

  20. Major Depression as a Complex Dynamic System

    PubMed Central

    Cramer, Angélique O. J.; van Borkulo, Claudia D.; Giltay, Erik J.; van der Maas, Han L. J.; Kendler, Kenneth S.; Scheffer, Marten; Borsboom, Denny

    2016-01-01

    In this paper, we characterize major depression (MD) as a complex dynamic system in which symptoms (e.g., insomnia and fatigue) are directly connected to one another in a network structure. We hypothesize that individuals can be characterized by their own network with unique architecture and resulting dynamics. With respect to architecture, we show that individuals vulnerable to developing MD are those with strong connections between symptoms: e.g., only one night of poor sleep suffices to make a particular person feel tired. Such vulnerable networks, when pushed by forces external to the system such as stress, are more likely to end up in a depressed state; whereas networks with weaker connections tend to remain in or return to a non-depressed state. We show this with a simulation in which we model the probability of a symptom becoming ‘active’ as a logistic function of the activity of its neighboring symptoms. Additionally, we show that this model potentially explains some well-known empirical phenomena such as spontaneous recovery as well as accommodates existing theories about the various subtypes of MD. To our knowledge, we offer the first intra-individual, symptom-based, process model with the potential to explain the pathogenesis and maintenance of major depression. PMID:27930698

  1. Early-onset Lafora body disease

    PubMed Central

    Turnbull, Julie; Girard, Jean-Marie; Lohi, Hannes; Chan, Elayne M.; Wang, Peixiang; Tiberia, Erica; Omer, Salah; Ahmed, Mushtaq; Bennett, Christopher; Chakrabarty, Aruna; Tyagi, Atul; Liu, Yan; Pencea, Nela; Zhao, XiaoChu; Scherer, Stephen W.; Ackerley, Cameron A.

    2012-01-01

    The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht–Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and

  2. High-throughput sequencing of the synaptome in major depressive disorder.

    PubMed

    Pirooznia, M; Wang, T; Avramopoulos, D; Potash, J B; Zandi, P P; Goes, F S

    2016-05-01

    Major depressive disorder (MDD) is among the leading causes of worldwide disability. Despite its significant heritability, large-scale genome-wide association studies (GWASs) of MDD have yet to identify robustly associated common variants. Although increased sample sizes are being amassed for the next wave of GWAS, few studies have as yet focused on rare genetic variants in the study of MDD. We sequenced the exons of 1742 synaptic genes previously identified by proteomic experiments. PLINK/SEQ was used to perform single variant, gene burden and gene set analyses. The GeneMANIA interaction database was used to identify protein-protein interaction-based networks. Cases were selected from a familial collection of early-onset, recurrent depression and were compared with screened controls. After extensive quality control, we analyzed 259 cases with familial, early-onset MDD and 334 controls. The distribution of association test statistics for the single variant and gene burden analyses were consistent with the null hypothesis. However, analysis of prioritized gene sets showed a significant association with damaging singleton variants in a Cav2-adaptor gene set (odds ratio=2.6; P=0.0008) that survived correction for all gene sets and annotation categories tested (empirical P=0.049). In addition, we also found statistically significant evidence for an enrichment of rare variants in a protein-based network of 14 genes involved in actin polymerization and dendritic spine formation (nominal P=0.0031). In conclusion, we have identified a statistically significant gene set and gene network of rare variants that are over-represented in MDD, providing initial evidence that calcium signaling and dendrite regulation may be involved in the etiology of depression.

  3. Serum proteomic profiling of major depressive disorder.

    PubMed

    Bot, M; Chan, M K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B W J H

    2015-07-14

    Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P < 0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology.

  4. Fluoxetine and sertraline dosages in major depression.

    PubMed

    Cantrell, R; Gillespie, W; Altshuler, L

    1999-01-01

    In a retrospective study, we sought to determine medication dosages usually prescribed to obtain euthymia in 59 outpatients with a diagnosis of major depression treated with fluoxetine or sertraline. Charts of veterans admitted to the outpatient mental health clinic at the West Los Angeles Veterans Hospital with a diagnosis of major depression and treated with either fluoxetine or sertraline were reviewed. Progress notes were analyzed for a 6-month time period after the initiation of the medication treatment, and improvement was rated by a physician blind to the drug used for treatment. No significant differences were found in overall response rates between the fluoxetine (81% responders) and sertraline (76% responders) groups. Eighty-one percent of the fluoxetine responders compared to 32% of sertraline responders were at the manufacturer's recommended starting dose (MRSD) at the time of clinical response. One-third of patients receiving sertraline were started on or rapidly titrated to more than 50 mg/day. When only those patients receiving an adequate trial of sertraline at 50 mg were considered, 47% required a dose increase to achieve a remission. These data suggest that 50 mg of sertraline may be inadequate for some patients to achieve a resolution of symptoms of major depression and that many clinicians currently prescribe in a manner suggesting that they believe the MRSD is a suboptimal dosage.

  5. Disrupted habenula function in major depression.

    PubMed

    Lawson, R P; Nord, C L; Seymour, B; Thomas, D L; Dayan, P; Pilling, S; Roiser, J P

    2017-02-01

    The habenula is a small, evolutionarily conserved brain structure that plays a central role in aversive processing and is hypothesised to be hyperactive in depression, contributing to the generation of symptoms such as anhedonia. However, habenula responses during aversive processing have yet to be reported in individuals with major depressive disorder (MDD). Unmedicated and currently depressed MDD patients (N=25, aged 18-52 years) and healthy volunteers (N=25, aged 19-52 years) completed a passive (Pavlovian) conditioning task with appetitive (monetary gain) and aversive (monetary loss and electric shock) outcomes during high-resolution functional magnetic resonance imaging; data were analysed using computational modelling. Arterial spin labelling was used to index resting-state perfusion and high-resolution anatomical images were used to assess habenula volume. In healthy volunteers, habenula activation increased as conditioned stimuli (CSs) became more strongly associated with electric shocks. This pattern was significantly different in MDD subjects, for whom habenula activation decreased significantly with increasing association between CSs and electric shocks. Individual differences in habenula volume were negatively associated with symptoms of anhedonia across both groups. MDD subjects exhibited abnormal negative task-related (phasic) habenula responses during primary aversive conditioning. The direction of this effect is opposite to that predicted by contemporary theoretical accounts of depression based on findings in animal models. We speculate that the negative habenula responses we observed may result in the loss of the capacity to actively avoid negative cues in MDD, which could lead to excessive negative focus.

  6. St. John's Wort for Major Depressive Disorder

    PubMed Central

    Maher, Alicia Ruelaz; Hempel, Susanne; Apaydin, Eric; Shanman, Roberta M.; Booth, Marika; Miles, Jeremy N. V.; Sorbero, Melony E.

    2016-01-01

    Abstract RAND researchers conducted a systematic review that synthesized evidence from randomized controlled trials of St. John's wort (SJW)—used adjunctively or as monotherapy—to provide estimates of its efficacy and safety in treating adults with major depressive disorder. Outcomes of interest included changes in depressive symptomatology, quality of life, and adverse effects. Efficacy meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. In total, 35 studies met inclusion criteria. There is moderate evidence, due to unexplained heterogeneity between studies, that depression improvement based on the number of treatment responders and depression scale scores favors SJW over placebo, and results are comparable to antidepressants. The existing evidence is based on studies testing SJW as monotherapy; there is a lack of evidence for SJW given as adjunct therapy to standard antidepressant therapy. We found no systematic difference between SJW extracts, but head-to-head trials are missing; LI 160 (0.3% hypericin, 1–4% hyperforin) was the extract with the greatest number of studies. Only two trials assessed quality of life. SJW adverse events reported in included trials were comparable to placebo, and were fewer compared with antidepressant medication; however, adverse event assessments were limited, and thus we have limited confidence in this conclusion. PMID:28083422

  7. Clinical efficacy of reboxetine in major depression.

    PubMed

    Schatzberg, A F

    2000-01-01

    The past decade has witnessed the advent of selective serotonin reuptake inhibitors (SSRIs) as first-line treatments for major depression. Still, there is considerable debate as to whether these agents are as effective or as potent as the first-generation tricyclic antidepressants (TCAs) or the mixed reuptake inhibitor, venlafaxine, all of which exert considerable effect on norepinephrine (NE) reuptake. Recently, reboxetine, a selective NE reuptake inhibitor (selective NRI), has been introduced in Europe. This drug has only a minimal affinity for muscarinic acetylcholine receptors and therefore causes less dry mouth, constipation, or other such effects than do the TCAs. Reboxetine does not block serotonin reuptake or alpha1 receptors and, thus, does not appear to produce significant nausea, diarrhea, or hypotension. Unlike other antidepressants, reboxetine appears to be nonsedating. Data on acute and long-term clinical efficacy and safety from double-blind, placebo-controlled, and active comparator studies with reboxetine are reviewed. These studies indicate that reboxetine is significantly more effective than placebo and as effective as fluoxetine in reducing depressive symptoms. Improvements in social adjustments were reported to be more favorable with reboxetine than with fluoxetine. Further, data from controlled clinical trials have shown that the side effect profile for reboxetine is relatively benign. The clinical implications of studies on reboxetine are discussed with an eye toward understanding the potential role NE reuptake blockers may play in the treatment of patients with major depression.

  8. Epigenetic Modifications of Major Depressive Disorder

    PubMed Central

    Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

    2016-01-01

    Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders. PMID:27527165

  9. Epigenetic Modifications of Major Depressive Disorder.

    PubMed

    Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A

    2016-08-05

    Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  10. POSTTRAUMATIC STRESS DISORDER INCREASES RISK FOR SUICIDE ATTEMPT IN ADULTS WITH RECURRENT MAJOR DEPRESSION

    PubMed Central

    Stevens, Daniel; Wilcox, Holly C.; MacKinnon, Dean F.; Mondimore, Francis M.; Schweizer, Barbara; Jancic, Dunya; Coryell, William H.; Weissman, Myrna M.; Levinson, Douglas F.; Potash, James B.

    2014-01-01

    Background Genetics of Recurrent Early-Onset Depression study (GenRED II) data were used to examine the relationship between posttraumatic stress disorder (PTSD) and attempted suicide in a population of 1,433 individuals with recurrent early-onset major depressive disorder (MDD). We tested the hypothesis that PTSD resulting from assaultive trauma increases risk for attempted suicide among individuals with recurrent MDD. Methods Data on lifetime trauma exposures and clinical symptoms were collected using the Diagnostic Interview for Genetic Studies version 3.0 and best estimate diagnoses of MDD, PTSD, and other DSM-IV Axis I disorders were reported with best estimated age of onset. Results The lifetime prevalence of suicide attempt in this sample was 28%. Lifetime PTSD was diagnosed in 205 (14.3%) participants. We used discrete time-survival analyses to take into account timing in the PTSD-suicide attempt relationship while adjusting for demographic variables (gender, race, age, and education level) and comorbid diagnoses prior to trauma exposure. PTSD was an independent predictor of subsequent suicide attempt (HR = 2.5, 95% CI: 1.6, 3.8; P < .0001). Neither assaultive nor nonassaultive trauma without PTSD significantly predicted subsequent suicide attempt after Bonferroni correction. The association between PTSD and subsequent suicide attempt was driven by traumatic events involving assaultive violence (HR = 1.7, 95% CI: 1.3, 2.2; P < .0001). Conclusions Among those with recurrent MDD, PTSD appears to be a vulnerability marker of maladaptive responses to traumatic events and an independent risk factor for attempted suicide. Additional studies examining differences between those with and without PTSD on biological measures might shed light on this potential vulnerability PMID:23893768

  11. Biomarkers for Major Depressive Disorder: Economic Considerations.

    PubMed

    Bogavac-Stanojevic, Natasa; Lakic, Dragana

    2016-11-01

    Preclinical Research Major depressive disorder (MDD) is a major psychiatric illness and it is predicted to be the second leading cause of disability by 2020 with a lifetime prevalence of about 13%. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used therapeutic class for MDD. However, response to SSRI treatment varies considerably between patients. Biomarkers of treatment response may enable clinicians to target the appropriate drug for each patient. Biomarkers need to have accuracy in real life, sensitivity, specificity, and relevance to depression. Introduction of MDD biomarkers into the health care system can increase the overall cost of clinical diagnosis of patients. Because of that, decisions to allocate health research funding must be based on drug effectiveness and cost-effectiveness. The assessment of MDD biomarkers should include reliable evidence of associated drug effectiveness, adverse events and consequences (reduced productivity and quality of life, disability) and effectiveness of alternative approaches, other drug classes or behavioral or alternative therapies. In addition, all the variables included in an economic model (probabilities, outcomes, and costs) should be based on reliable evidence gained from the literature-ideally meta-analyses-and the evidence should also be determined by informed and specific expert opinion. Early assessment can guide decisions about whether or not to continue test development, and ideally to optimize the process. Drug Dev Res 77 : 374-378, 2016. © 2016 Wiley Periodicals, Inc.

  12. Cortical thickness differences between bipolar depression and major depressive disorder

    PubMed Central

    Lan, Martin J; Chhetry, Binod Thapa; Oquendo, Maria A; Sublette, M Elizabeth; Sullivan, Gregory; Mann, J John; Parsey, Ramin V

    2014-01-01

    Objectives Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers. Methods Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups. Results Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within frontal and parietal lobes, and posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6–9.6% (cluster wise p-values from 1.0 e−4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5–8.2% (cluster wise p-values from 1.0 e−4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group. Conclusions Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders. PMID:24428430

  13. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Hughes, Jennifer L.; Stewart, Sunita M.; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J.

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  14. Metabolic depression in hibernation and major depression: an explanatory theory and an animal model of depression.

    PubMed

    Tsiouris, John A

    2005-01-01

    Metabolic depression, an adaptive biological process for energy preservation, is responsible for torpor, hibernation and estivation. We propose that a form of metabolic depression, and not mitochondrial dysfunction, is the process underlying the observed hypometabolism, state-dependent neurobiological changes and vegetative symptoms of major depression in humans. The process of metabolic depression is reactivated via differential gene expression in response to perceived adverse stimuli in predisposed persons. Behavior inhibition by temperament, anxiety disorders, genetic vulnerabilities, and early traumatic experiences predispose persons to depression. The proposed theory is supported by similarities in the presentation and neurobiology of hibernation in bears and major depression and explains the yet unexplained neurobiological changes of depression. Although, gene expression is suppressed in other hibernators by deep hypothermia, bears were chosen because they hibernate with mild hypothermia. Pre-hibernation in bears and major depression with atypical features are both characterized by fat storage through overeating, oversleeping, and decreased mobility. Hibernation in bears and major depression with melancholic features are characterized by withdrawal from the environment, lack of energy, loss of weight from not eating and burning stored fat, changes in sleep pattern, and the following similar neurobiological findings: reversible subclinical hypothyroidism; increased concentration of serum cortisol; acute phase protein response; low respiratory quotient; oxidative stress response; decreased neurotransmitter levels; and changes in cyclic-adenosine monophosphate-binding activity. Signaling systems associated with protein phosphorylation, transcription factors, and gene expression are responsible for the metabolic depression process during pre-hibernation and hibernation. Antidepressants and mood stabilizers interfere with the hibernation process and produce their

  15. Early-onset scoliosis: current treatment.

    PubMed

    Cunin, V

    2015-02-01

    Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

  16. Generalized Anxiety and Major Depressive syndrome ...

    EPA Pesticide Factsheets

    Objective: Environmental exposure to manganese (Mn) may cause generalized anxiety (GA) and major depression (MD) in residents living in Mn-exposed areas. Marietta and East Liverpool are two Ohio towns identified as having elevated levels of Mn. The objective was to determine if levels of Mn exposure were associated with levels of GA and MD.Participants and methods: 186 participants (Mean age: 55.0 ± 10.80) were examined. Levels of air-Mn were assessed over a period of ten years using U.S. EPA’s AERMOD dispersion model. Average air-Mn exposure was 0.53 μg/m3 in the two towns. The GA syndrome was comprised of anxiety, obsessive-compulsive, and phobic scales from the Symptom Checklist (SCL-90-R). The MD syndrome was comprised of depression, anxiety, and psychoticism scales also from the SCL-90-R. Linear regression models were used to determine the relationship between Mn and GA, MD and the specific components of each.Results: Elevated air-Mn was associated with GA (β= 0.240, p=0.002), and MD (β= 0.202, p=0.011). Air-Mn was associated with specific components of GA anxiety (β= 0.255, p=0.001), phobic anxiety (β= 0.159, p=0.046), and obsessive-compulsive (β= 0.197, p=0.013). Similarly, components of MD syndrome suggested an association as well: depression (β= 0.180, p=0.023), anxiety (β= 0.255, p=0.001), and psychoticism (β= 0.188, p=0.018). Conclusions: The results suggest that residents with elevated exposure to environmental Mn have elevated levels of

  17. Glutamate Metabolism in Major Depressive Disorder

    PubMed Central

    Abdallah, Chadi G.; Jiang, Lihong; De Feyter, Henk M.; Fasula, Madonna; Krystal, John H.; Rothman, Douglas L.; Mason, Graeme F.; Sanacora, Gerard

    2015-01-01

    Objective Emerging evidence suggests abnormalities in amino acid neurotransmitter function and impaired energy metabolism contribute to the underlying pathophysiology of Major Depressive Disorder (MDD). To test whether impairments in energetics and glutamate neurotransmitter cycling are present in MDD we used in vivo 13C magnetic resonance spectroscopy (13C MRS) to measure these fluxes in individuals diagnosed with MDD relative to non-depressed subjects. Method 1H MRS and 13C MRS data were collected on 23 medication-free MDD and 17 healthy subjects. 1H MRS provided total glutamate and GABA concentrations, and 13C MRS, coupled with intravenous infusion of [1-13C]-glucose, provided measures of the neuronal tricarboxylic acid cycle (VTCAN) for mitochondrial energy production, GABA synthesis, and glutamate/glutamine cycling, from voxels placed in the occipital cortex. Results Our main finding was that mitochondrial energy production of glutamatergic neurons was reduced by 26% in MDD subjects (t = 2.57, p = 0.01). Paradoxically we found no difference in the rate of glutamate/glutamine cycle (Vcycle). We also found a significant correlation between glutamate concentrations and Vcycle considering the total sample. Conclusions We interpret the reduction in mitochondrial energy production as being due to either mitochondrial dysfunction or a reduction in proper neuronal input or synaptic strength. Future MRS studies could help distinguish these possibilities. PMID:25073688

  18. Advances in biomarkers of major depressive disorder.

    PubMed

    Huang, Tiao-Lai; Lin, Chin-Chuen

    2015-01-01

    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Biomarkers are measurable indicators that could help diagnosing MDD or predicting treatment response. In this chapter, lipid profiles, immune/inflammation, and neurotrophic factor pathways that have long been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics and epigenetics of serotonin transport and its metabolism pathway, brain-derived neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis also revealed new biomarkers. Lastly, new techniques, such as proteomics and metabolomics, which allow researchers to approach the studying of MDD with new directions and make new discoveries are addressed. In the future, more data are needed regarding pathophysiology of MDD, including protein levels, single nucleotide polymorphism, epigenetic regulation, and clinical data in order to better identify reliable and consistent biomarkers for diagnosis, treatment choice, and outcome prediction.

  19. Sheehan's Syndrome Presenting as Major Depressive Disorder.

    PubMed

    Qadri, Mehmood I; Mushtaq, Mohsin Bin; Qazi, Iram; Yousuf, Sameena; Rashid, Aaliya

    2015-01-01

    Sheehan's syndrome or Simmond's disease is a rare endocrine disorder seen in clinical practice. The clinical spectrum is diverse and a high index of suspicion together with a good clinical acumen and proper diagnostic approach helps in early diagnosis and prompt treatment of this endocrinopathy. Sheehan's syndrome presenting as a major depressive disorder finds less mention in the literature. The patient discussed here is a 45-year-old female who had been on antidepressants and psychiatry follow up for a long time until she presented to our Out Patient Department (OPD), where she was evaluated in detail and diagnosed as a case of Sheehan's syndrome. The patient is doing well and is on a regular follow-up with us. Further studies are required to demystify the strength of this association in more detail and to elucidate the possible underlying mechanism.

  20. Major depression in primary care: making the diagnosis

    PubMed Central

    Ng, Chung Wai Mark; How, Choon How; Ng, Yin Ping

    2016-01-01

    Major depression is a common condition seen in the primary care setting, often presenting with somatic symptoms. It is potentially a chronic illness with considerable morbidity, and a high rate of relapse and recurrence. Major depression has a bidirectional relationship with chronic diseases, and a strong association with increased age and coexisting mental illnesses (e.g. anxiety disorders). Screening can be performed using clinical tools for major depression, such as the Patient Health Questionaire-2, Patient Health Questionaire-9 and Beck Depression Inventory, so that timely treatment can be initiated. An accurate diagnosis of major depression and its severity is essential for prompt treatment to reduce morbidity and mortality. This is the first of a series of articles that illustrates the approach to the management of major depression in primary care. Our next articles will cover suicide risk assessment in a depressed patient and outline the basic principles of management and treatment modalities. PMID:27872937

  1. [Early onset scoliosis. What are the options?].

    PubMed

    Farrington, D M; Tatay-Díaz, A

    2013-01-01

    The prognosis of children with progressive early onset scoliosis has improved considerably due to recent advances in surgical and non-surgical techniques and the understanding of the importance of preserving the thoracic space. Improvements in existing techniques and development of new methods have considerably improved the management of this condition. Derotational casting can be considered in children with documented progression of a <60° curve without previous surgical treatment. Both single and dual growing rods are effective, but the latter seem to offer better results. Hybrid constructs may be a better option in children who require a low-profile proximal anchor. The vertical expandable prosthetic titanium rib (VEPTR(®)) appears to be beneficial for patients with congenital scoliosis and fused ribs, and thoracic Insufficiency Syndrome. Children with medical comorbidities who may not tolerate repeated lengthenings should be considered for Shilla or Luque Trolley technique. Growth modulation using shape memory alloy staples or other tethers seem promising for mild curves, although more research is required to define their precise indications.

  2. Hippocampal neuroplasticity in major depressive disorder.

    PubMed

    Malykhin, N V; Coupland, N J

    2015-11-19

    One of the most replicated findings has been that hippocampus volume is decreased in patients with major depressive disorder (MDD). Recent volumetric magnetic resonance imaging (MRI) studies suggest that localized differences in hippocampal volume may be more prominent than global differences. Preclinical and post-mortem studies in MDD indicated that different subfields of the hippocampus may respond differently to stress and may also have differential levels of plasticity in response to antidepressant treatment. Advances in high-field MRI allowed researchers to visualize and measure hippocampal subfield volumes in MDD patients in vivo. The results of these studies provide the first in vivo evidence that hippocampal volume reductions in MDD are specific to the cornu ammonis and dentate gyrus hippocampal subfields, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. In this review we discuss how recent advances in neuroimaging allow researchers to further understand hippocampal neuroplasticity in MDD and how it is related to antidepressant treatment, memory function, and disease progression.

  3. Association of major depression with sexual dysfunction in men.

    PubMed

    Fabre, Louis F; Clayton, Anita H; Smith, Louis C; Goldstein, Irwin M; Derogatis, Leonard R

    2013-01-01

    The effect of type and severity of depression on sexual functioning was examined before treatment in 591 men with Major Depression (MDD) or Atypical Depression, as determined by percentage of subjects meeting Diagnostic and Statistical Manual, 4th Edition (DSM-IV) sexual dysfunction criteria (A and B only), and percentage with Derogatis Inventory of Sexual Function (DISF) scores greater than 1 standard deviation below normal. Sexual dysfunction rates were higher for MDD than for Atypical Depression. Depression affected DISF domains differently: orgasm was most impaired, whereas sexual desire was preserved. More severe depression resulted in greater sexual dysfunction.

  4. Effects of music on major depression in psychiatric inpatients.

    PubMed

    Hsu, Wei-Chi; Lai, Hui-Ling

    2004-10-01

    The study was to assess the effectiveness of soft music for treatment of major depressive disorder inpatients in Kaohsiung City, Taiwan. A pretest-posttest with a two-group repeated measures design was used. Patients with major depressive disorder were recruited through referred by the psychiatric physicians. Subjects listened to their choice of music for 2 weeks. Depression was measured with the Zung's Depression Scale before the study and at two weekly posttests. Using repeated measures ANCOVA, music resulted in significantly better depressive scores, as well as significantly better subscores of depression compared with controls. Depression improved weekly, indicating a cumulative dose effect. The findings provide evidence for psychiatric nurses to use soft music as an empirically based intervention for depressed inpatients.

  5. Motor Imagery in Unipolar Major Depression

    PubMed Central

    Bennabi, Djamila; Monnin, Julie; Haffen, Emmanuel; Carvalho, Nicolas; Vandel, Pierre; Pozzo, Thierry; Papaxanthis, Charalambos

    2014-01-01

    Background: Motor imagery is a potential tool to investigate action representation, as it can provide insights into the processes of action planning and preparation. Recent studies suggest that depressed patients present specific impairment in mental rotation. The present study was designed to investigate the influence of unipolar depression on motor imagery ability. Methods: Fourteen right-handed patients meeting DSM-IV criteria for unipolar depression were compared to 14 matched healthy controls. Imagery ability was accessed by the timing correspondence between executed and imagined movements during a pointing task, involving strong spatiotemporal constraints (speed/accuracy trade-off paradigm). Results: Compared to controls, depressed patients showed marked motor slowing on both actual and imagined movements. Furthermore, we observed greater temporal discrepancies between actual and mental movements in depressed patients than in healthy controls. Lastly, depressed patients modulated, to some extent, mental movement durations according to the difficulty of the task, but this modulation was not as strong as that of healthy subjects. Conclusion: These results suggest that unipolar depression significantly affects the higher stages of action planning and point out a selective decline of motor prediction. PMID:25538580

  6. Novel Augmentation Strategies in Major Depression.

    PubMed

    Martiny, Klaus

    2017-04-01

    Hypothesis The hypotheses of all the four included studies share the common idea that it is possible to augment the effect of antidepressant drug treatment by applying different interventions and with each intervention attain a clinically meaningful better effect compared to a control condition, and with minor side effects, thus improving the short- and medium-term outcome in major depression. Procedures Study design The basic study design has been the double blind randomised controlled trial (RCT). In the light therapy study, all patients were treated with sertraline for the whole of the study duration. In the first five weeks of the study, patients were randomised to treatment with either 60 minutes of bright white or 30 minutes of dim red light (sham condition). In the four weeks follow-up period, patients were treated with sertraline alone. In the Pindolol study, all patients were treated with venlafaxine and randomised to augmentation with either active or placebo matching pindolol tablets. In the PEMF study patients were continued on ongoing medication and randomised to augmentation with active or inactive (sham) 30 minutes daily PEMF treatment on weekdays. In the Chronos study all patients were treated with duloxetine and randomized to either a combination of three wake therapies with daily bright light treatment and sleep time stabilisation (wake group) or to daily exercise of minimum 30 minutes as an active control intervention (exercise group). The Chronos study was divided into: (1) a one-week run-in phase where duloxetine were started (and continued for the whole 29 week study period), (2) a one-week inpatient intervention phase where patient in the wake group did three wake therapies (sleep abstinence for the whole night and the following day until evening) in combination with daily light therapy and guidance on sleep time stabilisation and patients in the exercise group started a daily exercise program, (3) a seven week continuation phase where

  7. Major depressive disorder in children and adolescents after renal transplantation.

    PubMed

    Ghanizadeh, A; Mansoori, Y; Ashkani, H; Fallahzadeh, M H; Derakhshan, A; Shokrpour, N; Akhondzadeh, S

    2009-06-01

    This cross-sectional study evaluated the prevalence of major depressive disorder and depressive symptoms in children and adolescents after renal transplantation. A total of 71 patients who had undergone renal transplantation were interviewed in person using the Farsi (Persian) version of the Kiddie Schedule for Affective Disorders and Schizophrenia and Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria. Major depressive disorder, depressive symptoms, and suicidal behaviors were assessed. The rate of major depressive disorder was 2.8%; two-thirds of the patients had irritability; and approximately 40% had recurrent thoughts of death and suicidal ideation. The rate of major depressive disorder was lower than in other chronic diseases such as thallasemia or hemophilia; however, the rate of suicidal behaviors was high.

  8. Benchmarks for Psychotherapy Efficacy in Adult Major Depression

    ERIC Educational Resources Information Center

    Minami, Takuya; Wampold, Bruce E.; Serlin, Ronald C.; Kircher, John C.; Brown, George S.

    2007-01-01

    This study estimates pretreatment-posttreatment effect size benchmarks for the treatment of major depression in adults that may be useful in evaluating psychotherapy effectiveness in clinical practice. Treatment efficacy benchmarks for major depression were derived for 3 different types of outcome measures: the Hamilton Rating Scale for Depression…

  9. Mechanisms Underlying Neurocognitive Dysfunctions in Recurrent Major Depression

    PubMed Central

    Gałecki, Piotr; Talarowska, Monika; Anderson, George; Berk, Michael; Maes, Michael

    2015-01-01

    Recent work shows that depression is intimately associated with changes in cognitive functioning, including memory, attention, verbal fluency, and other aspects of higher-order cognitive processing. Changes in cognitive functioning are more likely to occur when depressive episodes are recurrent and to abate to some degree during periods of remission. However, with accumulating frequency and duration of depressive episodes, cognitive deficits can become enduring, being evident even when mood improves. Such changes in cognitive functioning give depression links to mild cognitive impairment and thereby with neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, and multiple sclerosis. Depression may then be conceptualized on a dimension of depression – mild cognitive impairment – dementia. The biological underpinnings of depression have substantial overlaps with those of neurodegenerative conditions, including reduced neurogenesis, increased apoptosis, reactive oxygen species, tryptophan catabolites, autoimmunity, and immune-inflammatory processes, as well as decreased antioxidant defenses. These evolving changes over the course of depressive episodes drive the association of depression with neurodegenerative conditions. As such, the changes in cognitive functioning in depression have important consequences for the treatment of depression and in reconceptualizing the role of depression in wider neuroprogressive conditions. Here we review the data on changes in cognitive functioning in recurrent major depression and their association with other central conditions. PMID:26017336

  10. Social functioning in major depressive disorder.

    PubMed

    Kupferberg, Aleksandra; Bicks, Lucy; Hasler, Gregor

    2016-10-01

    Depression is associated with social risk factors, social impairments and poor social functioning. This paper gives an overview of these social aspects using the NIMH Research and Domain Criteria 'Systems for Social Processes' as a framework. In particular, it describes the bio-psycho-social interplay regarding impaired affiliation and attachment (social anhedonia, hyper-sensitivity to social rejection, competition avoidance, increased altruistic punishment), impaired social communication (impaired emotion recognition, diminished cooperativeness), impaired social perception (reduced empathy, theory-of-mind deficits) and their impact on social networks and the use of social media. It describes these dysfunctional social processes at the behavioural, neuroanatomical, neurochemical and genetic levels, and with respect to animal models of social stress. We discuss the diagnostic specificity of these social deficit constructs for depression and in relation to depression severity. Since social factors are importantly involved in the pathogenesis and the consequences of depression, such research will likely contribute to better diagnostic assessments and concepts, treatments and preventative strategies both at the diagnostic and transdiagnostic level.

  11. [Relapse and insomnia in unipolar major depression].

    PubMed

    Falussy, Linda; Balla, Petra; Frecska, Ede

    2014-09-01

    The connection between mood and sleep disorders is highly complex and can be studied and interpreted in many respects. Epidemiologic data show that the co-occurrence of the two disorders is quite frequent. Thus an approach regarding them as a unit promotes biological psychiatric research by revealing new pathophysiological and therapeutic conclusions. Chronobiological results related to mood disorders have recently been described in excellent reviews including Hungarian ones. In the present review, the necessity of treatment of sleep disorders is evaluated in the context of relapse/remission/recurrence. Scientific data suggest that patients with insomnia have a ten-fold risk of developing depression, and insomnia plays an important role in depression relapses, recurrence of depressive episodes and becoming depression chronic. From neurobiological point of view, mood and sleep disorders have many features in common. Research has revealed decreased levels of melatonin and advanced sleep phases (shifted earlier) in depression, and altered and imbalanced monoaminergic pathways, and REM abnormalities in sleep disorders. Some authors suggest that REM abnormalities disappear along with the mood improvement, and the sleep structure can completely restore after remission. However, persistent abnormalities of REM sleep and slow wave sleep have also been found in remission, which increased the risk of the relapse and recurrence. Recently, there is an agreement as to the early treatment of insomnia can prevent the development of mood abnormalities. Alterations of cascades related to neural plasticity can also be a link between sleep and mood disorders. Neural plasticity is closely related to learning, sleeping, and cortisol regulation (coping with stress), and this draws the attention to comorbidity with further disorders (anxiety, dementia).

  12. HPA Axis Genetic Variation, Cortisol, and Psychosis in Major Depression

    PubMed Central

    Schatzberg, Alan F.; Keller, Jennifer; Tennakoon, Lakshika; Lembke, Anna; Williams, Gordon; Kraemer, Fredric B.; Sarginson, Jane E.; Lazzeroni, Laura C.; Murphy, Greer M.

    2013-01-01

    Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis over-activity in healthy controls and patients with severe forms of major depression has not been well explored but could explain risk for cortisol dysregulation. 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with nonpsychotic major depression (NPMD); and 29 healthy controls (HC). Collection of genetic material was added one third of the way into a larger study on cortisol, cognition, and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 6pm to 9am and for the assessment of alleles for 6 genes involved in HPA Axis regulation. Two of the 6 genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression, and psychosis, and medication status, only allelic variation for the glucocorticoid receptor gene (GR) accounted for significant variance for mean cortisol levels from 6pm to 1am (r2=.317) and from 1am to 9am (r2=.194). Interestingly, neither depression severity nor psychosis predicted cortisol variance. In addition, GR and corticotropin-releasing hormone receptor 1 (CRH-R1) contributed significantly to psychosis measures and CRH-R1 contributed significantly to depression severity rating. PMID:24166410

  13. Current understanding of the neurobiology of major depressive disorder.

    PubMed

    Chiriţă, Anca Livia; Gheorman, Victor; Bondari, Dan; Rogoveanu, Ion

    2015-01-01

    Depression is highly prevalent worldwide and associated with significant morbidity and mortality. Approximately 340 million people worldwide suffer from depression at any given time. Based on estimates from the World Health Organization (WHO), depression is responsible for the greatest proportion of burden associated with non-fatal health outcomes and accounts for approximately 12% total years lived with disability. Probably no single risk factor can be completely isolated in major depressive disorder (MDD), as interactions between many sources of vulnerability are the most likely explanation. Buttressing the identification of grief, demoralization, hopelessness and styles of psychological coping of the depressed patient are vital, ongoing scientific developments that flow from an increased understanding of this interplay amongst the immune system, endocrine system and brain. The rapidly accumulating body of neurobiological knowledge has catalyzed fundamental changes in how we conceptualize depressive symptoms and has important implications regarding the treatment and even prevention of depressive symptoms in patients.

  14. An IRT Analysis of the Symptoms of Major Depressive Disorder.

    PubMed

    Emmert-Aronson, Benjamin O; Brown, Timothy A

    2015-06-01

    This study examines the psychometric properties of a major depressive episode using a large sample (N = 2,907) of outpatients with mood and anxiety disorders. A two-parameter logistic model yielded item threshold and discrimination parameters. A two-group confirmatory factor analysis was used to evaluate gender bias. Item thresholds fell along a continuum with the core features of depressed mood and anhedonia, along with fatigue, endorsed at lower levels of depression, and change in appetite and suicidal ideation endorsed at more severe levels. Item discriminations were highest for depressed mood and anhedonia, and lowest for change in appetite and suicidal ideation. The data indicate that the symptoms of depression assess a range of severity, with varying precision in discriminating depression. No gender differences were observed. Three exploratory symptom sets were compared with the full symptom set for depression, offering quantitative evidence that can be used to modify the psychiatric classification system.

  15. Early Onset Hot Flashes May Signal Higher Heart Risks

    MedlinePlus

    ... medlineplus.gov/news/fullstory_164627.html Early Onset Hot Flashes May Signal Higher Heart Risks Study found ... 13, 2017 THURSDAY, April 13, 2017 (HealthDay News) -- Hot flashes may be more than a troublesome nuisance ...

  16. Blood-Based Biomarkers of Early-Onset Breast Cancer

    DTIC Science & Technology

    2015-10-01

    later ages. This inherited susceptibility to breast cancer might manifest as differences in gene expression patterns within key oncogenic pathways ...AWARD NUMBER: W81XWH-13-1-0214 TITLE: Blood-based biomarkers of early-onset breast cancer PRINCIPAL INVESTIGATOR: Nasim Ahmadiyeh...DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Blood-based biomarkers of early-onset breast cancer 5a. CONTRACT NUMBER W81XWH-13-1

  17. Major depressive disorder treatment guidelines in America and Europe.

    PubMed

    Davidson, Jonathan R T

    2010-01-01

    The various major American and European guidelines for the treatment of depression provide similar basic principles of treatment, which include individualizing the treatment plan, preparing the patient for potential long-term treatment, providing measurement-based care, and treating to remission. While the guidelines are all evidence-based, certain factors can influence differences in specific recommendations, such as the consensus group's composition, underlying mandates, and cultural attitudes. The similarities and differences among 6 sets of guidelines from Europe and the Americas published in the past decade are reviewed here (American Psychiatric Association, British Association for Psychopharmacology, Canadian Network for Mood and Anxiety Treatments, National Institute for Health and Clinical Excellence, Texas Medication Algorithm Project, and World Federation of Societies of Biological Psychiatry). In the guidelines, mild depression has the most variance in treatment recommendations; some, but not all, guidelines suggest that it may resolve with exercise or watchful waiting, but psychotherapy or antidepressants could be used if initial efforts fail. Moderate and severe major depression carry broadly similar recommendations among the guidelines. First-line treatment recommendations for moderate major depressive disorder include antidepressant monotherapy, psychotherapy, and the combination of both. Severe depression may require the combination of an antidepressant and an antipsychotic, electroconvulsive therapy, or the combination of an antidepressant and psychotherapy. Benzodiazepines play a very limited role in the treatment of depression; if the patient has catatonic depression, acutely suicidal depression, or depression with symptoms of anxiety, agitation, or insomnia, benzodiazepines are recommended by some guidelines for short-term treatment only.

  18. Omega-3 fatty acids in major depressive disorder.

    PubMed

    Freeman, Marlene P

    2009-01-01

    Patients with major depressive disorder have high rates of cardiovascular disease and other medical comorbidity. Omega-3 fatty acids, particularly those found in fish and seafood, have cardiovascular health benefits and may play an adjunctive role in the treatment of mood disorders. However, existing studies on omega-3 fatty acids in depression have limitations such as small sample sizes and a wide variance in study design, and results regarding efficacy are mixed. The preponderance of data from placebo-controlled treatment studies suggests that omega-3 fatty acids are a reasonable augmentation strategy for the treatment of major depressive disorder. More research is necessary before omega-3 supplements can be recommended as monotherapy for the treatment of depression. For many individuals with major depressive disorder, augmentation with omega-3 fatty acids should be considered, as general health benefits are well established and adjunctive use is low risk.

  19. Major Depressive Disorder in Adolescence: The Role of Subthreshold Symptoms

    ERIC Educational Resources Information Center

    Georgiades, Katholiki; Lewinsohn, Peter M.; Monroe, Scott M.; Seeley, John R.

    2006-01-01

    Objective: To examine the longitudinal association between individual subthreshold symptoms and onset of major depressive disorder (MDD) in adolescence. Method: Data for analysis come from the Oregon Adolescent Depression Project, a prospective epidemiological study of psychological disorders among adolescents, ages 14 to 18 years, from the…

  20. Major depression in panic disorder patients with comorbid social phobia.

    PubMed

    Reiter, S R; Otto, M W; Pollack, M H; Rosenbaum, J F

    1991-07-01

    Rates of depression among panic disorder patients are particularly elevated in patients with comorbid social phobia. However, it is unclear whether this association is specific to social phobia, or whether any comorbid anxiety disorder increases the risk of depression. We assessed 100 panic disorder patients and found a significantly higher incidence of lifetime major depression for panic patients with comorbid social phobia or generalized anxiety disorder (GAD). Panic patients with comorbid social phobia had significantly higher scores on measures of dysfunctional attitudes and lower scores on measures of assertiveness; these variables may mediate the link between social phobia and depression in this population.

  1. Neurobiology of chronic mild stress: Parallels to major depression

    PubMed Central

    Hill, Matthew N.; Hellemans, Kim G.C.; Verma, Pamela; Gorzalka, Boris B.; Weinberg, Joanne

    2016-01-01

    The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression. PMID:22776763

  2. Mitochondrial dysfunction, oxidative stress, and major depressive disorder

    PubMed Central

    Tobe, Edward H

    2013-01-01

    There is controversy about depression being a physical illness, in part because a reproducible, sensitive, and specific biologic marker is not available. However, there is evidence that mitochondrial dysfunction and oxidative stress may be associated with abnormal brain function and mood disorders, such as depression. This paper reviews selected human and animal studies providing evidence that intracellular mitochondrial metabolic dysfunction in specific brain regions is associated with major depressive disorder. This supports the hypothesis that chronic mitochondrial dysfunction in specific tissues may be associated with depression. Evaluation of mitochondrial dysfunction in specific tissues may broaden the perspective of depression beyond theories about neurotransmitters or receptor sites, and may explain the persistent signs and symptoms of depression. PMID:23650447

  3. Additive genetic contribution to symptom dimensions in major depressive disorder.

    PubMed

    Pearson, Rahel; Palmer, Rohan H C; Brick, Leslie A; McGeary, John E; Knopik, Valerie S; Beevers, Christopher G

    2016-05-01

    Major depressive disorder (MDD) is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum-likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with MDD (N = 1,558) who participated in the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed 4 depression symptom components: (a) appetite, (b) core depression symptoms (e.g., depressed mood, anhedonia), (c) insomnia, and (d) anxiety. These symptom dimensions were associated with SNP-based heritability (hSNP2) estimates of 30%, 14%, 30%, and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts. (PsycINFO Database Record

  4. Immunological differences between patients with major depression and somatization syndrome.

    PubMed

    Rief, W; Pilger, F; Ihle, D; Bosmans, E; Egyed, B; Maes, M

    2001-12-31

    There is some evidence that major depression is accompanied by activation of the inflammatory response system (IRS). There is also evidence that proinflammatory cytokines and induction of IRS activation are associated with sickness behavior in experimental animals. However, no research has examined the IRS in somatization disorder. The aim of this study was to examine possible immunological differences between major depression, somatization and healthy controls. We measured the following IRS variables in patients with major depression (n=36), somatization syndrome (SSI-8; n=37), major depression and somatization (n=40) and healthy controls (n=37): interleukin-6 (IL-6); interleukin-1-receptor-antagonist (IL-1RA); plasma soluble interleukin-6 receptor (IL-6R); soluble suppressor/cytotoxic antigen (CD8); leukemia inhibitory factor (LIF-R); and Clara cell protein (CC16), an endogenous anticytokine. Serum CD8 concentrations were significantly increased in patients with major depression compared with concentrations in patients with somatization syndrome, whereas concentrations in normal controls were intermediate between those of the two groups of patients. Serum CC16 was significantly lower in major depression than in healthy controls. The highest CC16 scores were found in patients with somatization syndrome. Somatizing patients have significantly lower serum IL-6 values than normal controls and depressed patients. The present results indicate (1) an activation of the IRS in depression with signs of T-cell activation (increased CD8), monocytic activation (IL-1RA) and a lowered anti-inflammatory capacity of the serum (lower CC16) and (2) an immune alteration in somatizing syndrome, such as monocytic activation (increased IL-1RA) and indicators of lowered T-lymphocytic activity (lowered CD8 and IL-6). These results suggest different immune alterations in somatization syndrome and depression.

  5. Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder.

    PubMed

    Sacchet, Matthew D; Livermore, Emily E; Iglesias, Juan Eugenio; Glover, Gary H; Gotlib, Ian H

    2015-09-01

    Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.

  6. Discriminating Between Bipolar Disorder and Major Depressive Disorder.

    PubMed

    Vöhringer, Paul A; Perlis, Roy H

    2016-03-01

    Rates of misdiagnosis between major depressive disorder and bipolar disorder have been reported to be substantial, and the consequence of such misdiagnosis is likely to be a delay in achieving effective control of symptoms, in some cases spanning many years. Particularly in the midst of a depressive episode, or early in the illness course, it may be challenging to distinguish the 2 mood disorders purely on the basis of cross-sectional features. To date, no useful biological markers have been reliably shown to distinguish between bipolar disorder and major depressive disorder.

  7. HLA region excluded by linkage analyses of early onset periodontitis

    SciTech Connect

    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  8. Verbal fluency in Alzheimer's disease, Parkinson's disease, and major depression

    PubMed Central

    de Araujo, Narahyana Bom; Barca, Maria Lage; Engedal, Knut; Coutinho, Evandro Silva Freire; Deslandes, Andrea Camaz; Laks, Jerson

    2011-01-01

    OBJECTIVE: To compare verbal fluency among Alzheimer's disease, Parkinson's disease, and major depression and to assess the sociodemographic and clinical factors associated with the disease severity. METHODS: Patients from an outpatient university center with a clinical diagnosis of Alzheimer's disease, Parkinson's disease or major depression were studied. Severity was staged using the Hoehn & Yahr scale, the Hamilton Depression scale and the Clinical Dementia Rating for Parkinson's disease, major depression, and Alzheimer's disease, respectively. All subjects were tested with the Mini-Mental State Examination, the digit span test, and the verbal fluency test (animals). We fit four types of regression models for the count variable: Poisson model, negative binomial model, zero-inflated Poisson model, and zero-inflated negative binomial model. RESULTS: The mean digit span and verbal fluency scores were lower in patients with Alzheimer's disease (n = 34) than in patients with major depression (n = 52) or Parkinson's disease (n = 17) (p<0.001). The average number of words listed was much lower for Alzheimer's disease patients (7.2 words) compared to the patients presenting with major depression (14.6 words) or Parkinson's disease (15.7 words) (KW test = 32.4; p<0.01). Major depression and Parkinson's disease groups listed 44% (ROM = 1.44) and 48% (ROM = 1.48) more words, respectively, compared to those patients with Alzheimer's disease; these results were independent of age, education, disease severity and attention. Independently of diagnosis, age, and education, severe disease showed a 26% (ROM = 0.74) reduction in the number of words listed when compared to mild cases. CONCLUSIONS: Verbal fluency provides a better characterization of Alzheimer's disease, major depression, and Parkinson's disease, even at later stages. PMID:21655757

  9. Gender differences in the symptoms of major depressive disorder.

    PubMed

    Romans, Sarah E; Tyas, Jeanette; Cohen, Marsha M; Silverstone, Trevor

    2007-11-01

    Data from the Canadian Community Health Survey 1.2 were used for a gender analysis of individual symptoms and overall rates of depression in the preceding 12 months. Major depressive disorder was assessed using the Composite International Diagnostic Interview in this national, cross-sectional survey. The female to male ratio of major depressive disorder prevalence was 1.64:1, with n = 1766 having experienced depression (men 668, women 1098). Women reported statistically more depressive symptoms than men (p < 0.001). Depressed women were more likely to report "increased appetite" (15.5% vs. 10.7%), being "often in tears" (82.6% vs. 44.0%), "loss of interest" (86.9% vs. 81.1%), and "thoughts of death" (70.3% vs. 63.4%). No significant gender differences were found for the remaining symptoms. The data are interpreted against women's greater tendency to cry and to restrict food intake when not depressed. The question is raised whether these items preferentially bias assessment of gender differences in depression, particularly in nonclinic samples.

  10. Neurokinin-1 receptors are decreased in major depressive disorder.

    PubMed

    Stockmeier, Craig A; Shi, Xiaochun; Konick, Lisa; Overholser, James C; Jurjus, George; Meltzer, Herbert Y; Friedman, Lee; Blier, Pierre; Rajkowska, Grazyna

    2002-07-02

    Treatment with an antagonist at the neurokinin-1 (NK-1) receptor may alleviate depression, however the brain region(s) in which the NK-1 receptor antagonist exerts its therapeutic effect is unknown. [125I]BH-Substance P was used to measure NK-1 receptors postmortem in cytoarchitectonically defined areas of rostral orbitofrontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may thus involve NK-1 receptors in prefrontal cortex.

  11. Major depression in the transition to adulthood: risks and impairments.

    PubMed

    Reinherz, H Z; Giaconia, R M; Hauf, A M; Wasserman, M S; Silverman, A B

    1999-08-01

    An ongoing longitudinal community study (N = 375) examined childhood risks and later adult impairments associated with 1-year Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) diagnoses of major depression during the transition to adulthood. Risks from birth to age 9 were reported by mothers, participants, and teachers. Teacher-reported hostility at age 6 predicted later depression. At age 9, self-perceptions of anxiety/depression, unpopularity, familial rejection, and abuse were potent risks. For men, neonatal and childhood health problems predicted later depression. For women, risks included family constellation, parental death, and poor academic achievement at age 9. Men and women who were depressed at age 18, age 21, or both demonstrated extensive psychosocial impairments in early adulthood, including poor overall functioning, interpersonal and behavioral problems, low self-esteem, and suicidality.

  12. Iowa Gambling Task in patients with early-onset Parkinson's disease: strategy analysis.

    PubMed

    Gescheidt, Tomáš; Czekóová, Kristína; Urbánek, Tomáš; Mareček, Radek; Mikl, Michal; Kubíková, Radka; Telecká, Sabina; Andrlová, Hana; Husárová, Ivica; Bareš, Martin

    2012-12-01

    The aim of our study was to analyse decision making in early-onset Parkinson's disease (PD) patients performing the Iowa Gambling Task (IGT). We compared 19 patients with early-onset PD (≤ 45 years) on dopaminergic medication (no evidence of depression, dementia, executive dysfunction according to the Tower of London test and the Stroop test, or pathological gambling) with 20 age-matched controls. A computer version of the IGT was employed. The PD patients achieved slightly lower IGT scores than the control group. A detailed analysis based on 'shift frequencies' between the individual decks showed that the patients tended to change their preferences for the decks more frequently, with a higher preference for the 'disadvantageous' deck B. Control subjects seemed to develop a more effective strategy. These differences could be caused by the poorer ability of the patients to develop any strategy at all. We observed changes in decision making during IGT performance in patients with early-onset PD, although they had no executive dysfunction as measured by established neuropsychological tests. The more detailed analysis employed in the present study could lead to a more accurate study of IGT performance and application of IGT in clinical practice.

  13. Sensitivity and specificity of the Major Depression Inventory in outpatients

    PubMed Central

    Cuijpers, Pim; Dekker, Jack; Noteboom, Annemieke; Smits, Niels; Peen, Jaap

    2007-01-01

    Background The Major Depression Inventory (MDI) is a new, brief, self-report measure for depression based on the DSM-system, which allows clinicians to assess the presence of a depressive disorder according to the DSM-IV, but also to assess the severity of the depressive symptoms. Methods We examined the sensitivity, specificity, and psychometric qualities of the MDI in a consecutive sample of 258 psychiatric outpatients. Of these patients, 120 had a mood disorder (70 major depression, 49 dysthymia). A total of 139 subjects had a comorbid axis-I diagnosis, and 91 subjects had a comorbid personality disorder. Results Crohnbach's alpha of the MDI was a satisfactory 0.89, and the correlation between the MDI and the depression subscale of the SCL-90 was 0.79 (p < .001). Subjects with major depressive disorder (MDD) had a significantly higher MDI score than subjects with anxiety disorders (but no MDD), dysthymias, bipolar, psychotic, other neurotic disorders, and subjects with relational problems. In ROC analysis we found that the area under the curve was 0.68 for the MDI. A good cut-off point for the MDI seems to be 26, with a sensitivity of 0.66, and a specificity of 0.63. The indication of the presence of MDD based on the MDI had a moderate agreement with the diagnosis made by a psychiatrist (kappa: 0.26). Conclusion The MDI is an attractive, brief depression inventory, which seems to be a reliable tool for assessing depression in psychiatric outpatients. PMID:17688685

  14. Transcranial magnetic stimulation for the treatment of major depression

    PubMed Central

    Janicak, Philip G; Dokucu, Mehmet E

    2015-01-01

    Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination) are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse). Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability. PMID:26170668

  15. Anticipatory pleasure predicts motivation for reward in major depression.

    PubMed

    Sherdell, Lindsey; Waugh, Christian E; Gotlib, Ian H

    2012-02-01

    Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals' motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking.

  16. Anticipatory Pleasure Predicts Motivation for Reward in Major Depression

    PubMed Central

    Sherdell, Lindsey; Waugh, Christian E.; Gotlib, Ian H.

    2012-01-01

    Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals’ motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking. PMID:21842963

  17. Major depressive disorder induced by prolactinoma--a case report.

    PubMed

    Liao, Wei-Ting; Bai, Ya-Mei

    2014-01-01

    Prolactinomas, the most common type of pituitary tumor, can induce hyperprolactinemia and cause some psychiatric symptoms, such as anxiety, depression and even psychotic symptoms. However, in previous case reports, no information about estrogen levels was mentioned. Here, we present a 48-year-old female patient who had a recurrent episode of major depressive disorder (MDD) and amenorrhea. Hyperprolactinemia (167 ng/ml), low estrogen (15.31 pg/ml) and a pituitary prolactinoma were found by MRI. After a dopamine agonist (Dostinex) and aripiprazole were prescribed, the patient's depressed mood remitted and her menstruation normalized. The possible mechanism of MDD induced by prolactinoma is discussed.

  18. Impact of lifestyle and psychological stress on the development of early onset breast cancer.

    PubMed

    Li, Ping; Huang, Jialing; Wu, Huina; Fu, Cuixia; Li, Yun; Qiu, Jiajia

    2016-12-01

    The present study aimed to investigate risk factors for early onset breast cancer that are related to lifestyle and psychological stress. A comparative case-control study was performed among patients from the Department of Breast Surgery in Shanghai Cancer Center of Fudan University. The information regarding risk factors associated with the development of early onset breast cancer was collected using a questionnaire in a face-to-face interview. The distribution of the risk factors associated with the development of early onset breast cancer between the patient group and the control group was analyzed with logistic regression. A total of 582 cases of young patients (≤40 years old) with breast cancer and 540 controls of young patients (≤40 years old) with benign breast disease were included in this study. The risk factors for breast cancer in young women include age at first birth (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.98), history of breast cancer in an immediate family member (OR = 2.36, 95% CI: 1.14-4.89), history of genital surgery (OR = 2.11, 95% CI: 1.16-3.82), active and passive smoking in daily life or the environment (OR = 1.64, 95% CI: 1.19-2.25), weekly intake of soy products (OR = 1.24, 95% CI: 1.02-1.49), use of household cooking oil (OR = 2.04, 95% CI: 1.04-4.00), disharmonious marital status (OR = 1.16, 95% CI: 1.06-1.26), frequent depression (OR = 1.32, 95% CI: 1.00-1.75), and negative emotional experiences (OR = 1.15, 95% CI: 1.03-1.29). Our study could provide the basis for risk assessment and preventive interventions for early onset breast cancer.

  19. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

    PubMed Central

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status. PMID:26122586

  20. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    PubMed

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  1. The relationship between fibromyalgia and major depressive disorder.

    PubMed

    Hudson, J I; Pope, H G

    1996-05-01

    Looking at the results of the seven types of studies discussed previously, it appears that there is strong evidence for an association between fibromyalgia and major depressive disorder on the basis of (1) overlapping symptomatology, (2) similar pattern of comorbid disorders, and (3) high rates of major depressive disorder among relatives of patients with fibromyalgia. There is additional support for an association on the basis of responses to psychological tests and rating scales and the high lifetime rates of mood disorders in fibromyalgia. Two lines of evidence, (1) response to antidepressant medications and (2) response to biologic tests, offer little evidence either for or against an association. On balance, then the weight of the evidence favors an association between fibromyalgia and major depressive disorder. We therefore turn to an analysis of the nature of the association.

  2. [Gap junctions: A new therapeutic target in major depressive disorder?].

    PubMed

    Sarrouilhe, D; Dejean, C

    2015-11-01

    Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder.

  3. Functional and structural brain correlates of risk for major depression in children with familial depression

    PubMed Central

    Chai, Xiaoqian J.; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia A.; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de los Angeles, Carlo; Whitfield-Gabrieli, Susan; Gabrieli, John D.E.

    2015-01-01

    Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression. PMID:26106565

  4. sigma-1 receptors in major depression and anxiety.

    PubMed

    Kulkarni, Shrinivas K; Dhir, Ashish

    2009-07-01

    Major depression and anxiety are two of the major psychiatric disorders that have some overlapping pathophysiologies, the most significant being the dysfunction in the monoaminergic, GABAergic and glutamatergic systems. A large number of drugs that alter these neurotransmitter levels/systems are effective in the treatment of major depression and anxiety. However, full remission of the clinical symptoms has not been achieved, perhaps owing to the complex pathophysiology of the diseases. Thus, the search for newer targets and target-specific drugs continues. Recently, the role of sigma-receptors, particularly the sigma-1 receptor subtype, has been identified as a target for the pathophysiology of neuropsychiatric disorders, and sigma-1 receptor modulators are considered to be the drugs of the future for the treatment of major depression and anxiety. The present review attempts to discuss the role of sigma-1 receptors in the pathophysiology of major depression and anxiety and also tries to position the use of its receptor modulators in the treatment of these two major disorders. The role of sigma-1 receptors in the mechanism of antidepressant action of venlafaxine, bupropion, neurosteroids and one of the herbal antidepressants, berberine, is reviewed. Although, sigma-1 receptor modulators may be future therapeutic options, either as individual agents or adjuvants in the treatment of mental disorders, the topic needs further preclinical and clinical exploration.

  5. Vilazodone in the treatment of major depressive disorder: efficacy across symptoms and severity of depression

    PubMed Central

    Sambunaris, Angelo; Edwards, John; Ruth, Adam; Robinson, Donald S.

    2014-01-01

    Vilazodone is a potent selective serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder in adults. To assess the efficacy of vilazodone across a range of symptoms and severities of depression, data from two phase III, 8-week, randomized, double-blind, placebo-controlled trials were pooled for analysis. Overall improvement in depressive symptoms measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Depression Rating Scale was statistically significant (P<0.05) for vilazodone treatment compared with placebo as early as Week 1 and continued throughout double-blind treatment. Vilazodone treatment compared with placebo showed significant improvement on all 10 individual MADRS symptom items at end of treatment (P<0.01). Rates of response and remission were significantly greater in the vilazodone group relative to the placebo group, with numbers needed to treat ranging from eight to nine for response and 12–17 for remission. Between-group treatment differences in MADRS and the other outcome measures were similar among all depression subgroups, with no consistent pattern associated with depression severity. These findings support the efficacy of vilazodone across a broad range of depressive symptoms and severities for the treatment of major depressive disorder. PMID:24247740

  6. Vilazodone in the treatment of major depressive disorder: efficacy across symptoms and severity of depression.

    PubMed

    Khan, Arif; Sambunaris, Angelo; Edwards, John; Ruth, Adam; Robinson, Donald S

    2014-03-01

    Vilazodone is a potent selective serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder in adults. To assess the efficacy of vilazodone across a range of symptoms and severities of depression, data from two phase III, 8-week, randomized, double-blind, placebo-controlled trials were pooled for analysis. Overall improvement in depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Depression Rating Scale was statistically significant (P<0.05) for vilazodone treatment compared with placebo as early as Week 1 and continued throughout double-blind treatment. Vilazodone treatment compared with placebo showed significant improvement on all 10 individual MADRS symptom items at end of treatment (P<0.01). Rates of response and remission were significantly greater in the vilazodone group relative to the placebo group, with numbers needed to treat ranging from eight to nine for response and 12-17 for remission. Between-group treatment differences in MADRS and the other outcome measures were similar among all depression subgroups, with no consistent pattern associated with depression severity. These findings support the efficacy of vilazodone across a broad range of depressive symptoms and severities for the treatment of major depressive disorder.

  7. Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder.

    PubMed

    Berent, Dominika; Zboralski, Krzysztof; Orzechowska, Agata; Gałecki, Piotr

    2014-01-01

    The clinical implications of thyroid hormones in depression have been studied extensively and still remains disputable. Supplementation of thyroid hormones is considered to augment and accelerate antidepressant treatment. Studies on the role of thyroid hormones in depression deliver contradictory results. Here we assess theirs impact on depression severity and final clinical outcome in patients with major depression. Thyrotropin, free thyroxine (FT4), and free triiodothyronine (FT3) concentrations were measured with automated quantitative enzyme immunoassay. Depression severity and final clinical outcome were rated with 17-itemic Hamilton Rating Scale for Depression [HDRS(17)] and Clinical Global Impression Scales for severity and for improvement (CGIs, CGIi). FT3 and FT4 concentrations were significantly positively correlated with clinical improvement evaluated with CGIi (R = 0.38, P = 0.012; R = 0.33, P = 0.034, respectively). There was a significant correlation between FT4 concentrations and depression severity assessed in HDRS(17) (R = 0.31, P = 0.047). Male patients presented significantly higher FT3 serum levels (Z = 2.34, P = 0.018) and significantly greater clinical improvement (Z = 2.36, P = 0.018) when compared to female patients. We conclude that free thyroid hormones concentrations are associated with depression severity and have an impact on final clinical outcome. It can be more efficient to augment and accelerate the treatment of major depressive disorder with triiodothyronine instead of levothyroxine because of individual differences in thyroid hormones metabolism.

  8. An astroglial basis of major depressive disorder? An overview.

    PubMed

    Wang, Qian; Jie, Wei; Liu, Ji-Hong; Yang, Jian-Ming; Gao, Tian-Ming

    2017-03-20

    Depression is a chronic, recurring, and serious mood disorder that afflicts up to 20% of the global population. The monoamine hypothesis has dominated our understanding of the pharmacotherapy of depression for more than half a century; however, our understanding of the pathophysiology and pathogenesis of major depression has lagged far behind. Astrocytes are the most abundant and versatile cells in the brain, participating in most, if not all, of brain functions as both a passive housekeeper and an active player. Mounting evidence from clinical, preclinical and post-mortem studies has revealed a decrease in the number or density of astrocytes and morphological and functional astroglial atrophy in patients with major depressive disorder (MDD) and in animal models of depression. Furthermore, currently available antidepressant treatments at least partially exert their therapeutic effects on astrocytes. More importantly, dysfunctional astrocytes lead to depressive-like phenotypes in animals. Together, current studies point to astroglial pathology as the potential root cause of MDD. Thus, a shift from a neuron-centric to an astrocyte-centric cause of MDD has gained increasing attention during the past two decades. Here we will summarize the current evidence supporting the hypothesis that MDD is a disease of astrocyte pathology and highlight previous studies on promising strategies that directly target astrocytes for the development of novel antidepressant treatments.

  9. Early onset myotonic dystrophy in association with polyneuropathy.

    PubMed Central

    Paramesh, K; Smith, B H; Kalyanaraman, K

    1975-01-01

    A patient with early onset of myotonic dystrophy, with associated neuropathy and epilepsy, is presented. It is postulated that his disorder was inherited through a recessive, pleomorphic gene. His differential diagnosis is discussed and the literature reviewed. The clinical variability of myotonic dystrophy is stressed and the diagnostic difficulties encountered in the younger age group. Images PMID:173806

  10. Operational Thought in Alzheimer's Disease Early Onset and SDAT.

    ERIC Educational Resources Information Center

    Emery, Olga B.; Breslau, Lawrence D.

    For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

  11. Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

    ERIC Educational Resources Information Center

    McIntosh, David E.; Trotter, Jeffrey S.

    2006-01-01

    Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

  12. 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…

  13. Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Rovet, Joanne F.; And Others

    1988-01-01

    Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

  14. EFEMP1 is not associated with sporadic early onset drusen.

    PubMed

    Sauer, C G; White, K; Kellner, U; Rudolph, G; Jurklies, B; Pauleikhoff, D; Weber, B H

    2001-03-01

    The early onset of multiple drusen in the posterior pole of the retina is characteristic of a group of macular dystrophies often referred to as dominant or radial drusen. At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity. Here, we present a further evaluation of the role of EFEMP1 in the pathogenesis of sporadic forms of early onset drusen. We analyzed all coding exons of the EFEMP1 gene by SSCP analysis in 14 unrelated individuals with early onset of multiple drusen and no apparent family history of the disease. In this patient group, we did not detect the R345W mutation or any other disease-associated mutation. Three different polymorphisms and two intragenic polymorphic repeats were present in similar frequencies in the patients and control individuals. We conclude that EFEMP1 is unlikely to be involved in the disease in this patient group. This suggests that mutations in a different as yet unknown gene or genes may lead to the early onset drusen phenotype.

  15. Diagnosing Depression in Chronic Pain Patients: DSM-IV Major Depressive Disorder vs. Beck Depression Inventory (BDI)

    PubMed Central

    2016-01-01

    Background Diagnosing depression in chronic pain is challenging due to overlapping somatic symptoms. In questionnaires, such as the Beck Depression Inventory (BDI), responses may be influenced more by pain than by the severity of depression. In addition, previous studies have suggested that symptoms of negative self-image, a key element in depression, are uncommon in chronic pain-related depression. The object of this study is to assess the relationship of the somatic and cognitive-emotional items of BDI with the diagnosis of depression, pain intensity, and disability. Methods One hundred consecutive chronic pain patients completed the Structured Clinical Interview for DSM Disorders (SCID) for the diagnosis of major depressive disorder (MDD) according to DSM-IV. Two subscales of BDI (negative view of self and somatic-physical function) were created according to the factor model presented by Morley. Results In the regression analysis, the somatic-physical function factor associated with MDD, while the negative view of self factor did not. Patients with MDD had higher scores in several of the BDI items when analysed separately. Insomnia and weight loss were not dependent on the depression diagnosis. Limitations The relatively small sample size and the selected patient sample limit the generalisability of the results. Conclusions Somatic symptoms of depression are also common in chronic pain and should not be excluded when diagnosing depression in pain patients. Regardless of the assessment method, diagnosing depression in chronic pain remains a challenge and requires careful interpretation of symptoms. PMID:27008161

  16. Exercise as an augmentation strategy for treatment of major depression.

    PubMed

    Trivedi, Madhukar H; Greer, Tracy L; Grannemann, Bruce D; Chambliss, Heather O; Jordan, Alexander N

    2006-07-01

    The use of augmentation strategies among patients with major depression is increasing because rates of complete remission with standard antidepressant monotherapy are quite low. Clinical and neurobiological data suggest that exercise may be a good candidate for use as an augmentation treatment for depression. This pilot study examined the use of exercise to augment antidepressant medication in patients with major depression. Seventeen patients with incomplete remission of depressive symptoms began a 12-week exercise program while continuing their antidepressant medication (unchanged in type or dose). Individual exercise prescriptions were calculated based on an exercise dose consistent with currently recommended public health guidelines. The exercise consisted of both supervised and home-based sessions. The 17-item Hamilton Rating Scale for Depression (HRSD17) and the Inventory of Depressive Symptomatology-Self-Report (IDS-SR30) were used to assess symptoms of depression on a weekly basis. Intent-to-treat analyses yielded significant decreases on both the HRSD17 (5.8 points, p < 0.008) and IDS-SR30 (13.9 points, p < 0.002). For patients who completed the study (n = 8), HRSD17 scores decreased by 10.4 points and IDS-SR30 scores decreased by 18.8 points. This study provides preliminary evidence for exercise as an effective augmentation treatment for antidepressant medication. This is a lower-cost augmentation strategy that has numerous health benefits and may further reduce depressive symptoms in partial responders to antidepressant treatment. Practical tips on how practitioners can use exercise to enhance antidepressant treatment are discussed. Longer-term use of exercise is also likely to confer additional health benefits for this population.

  17. Night Eating Syndrome in Major Depression and Anxiety Disorders

    PubMed Central

    KÜÇÜKGÖNCÜ, Suat; BEŞTEPE, Emrem

    2014-01-01

    Introduction The purpose of this study is to investigate the prevalence and the clinical features of night eating syndrome (NES) in patients with depression and anxiety disorders. Method The study was conducted at Bakırköy State Hospital for Mental Health and Neurological Disorders. Three-hundred out-patients who had major depression (MD), panic disorders (PD), general anxiety disorders (GAD) and obsessive-compulsive disorders (OCD) participated in the study. The semi-structured socio-demographic form, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Night Eating Questionnaire, and NES Evaluation Questionnaire were implemented. Results In our sample, the prevalence of the NES was 15.7% (n=47). NES frequency was significantly higher in the patients diagnosed with major depression (MD 22%, GAD 7.8%, OCD 12.5%, PD 14%). Smoking, presence of past suicide attempts, rates of antipsychotic drugs use, and average scores of body mass index (BMI) were significantly higher in the patients who had NES. In this sample, depression, BMI, and smoking were found to be determinants of NES. Conclusion This study shows that NES may be frequently observed in patients admitted to psychiatric clinics, especially in those with major depression. Evaluation of NES in psychiatric patients may help the treatment of the primary psychopathology and prevent the adverse effects, like weight gain, which may reduce the quality of life.

  18. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  19. Reduced Anterior Cingulate Cortex Glutamatergic Concentrations in Childhood Major Depression

    ERIC Educational Resources Information Center

    Mirza, Yousha; Tang, Jennifer; Russell, Aileen; Banerjee, S. Preeya; Bhandari, Rashmi; Ivey, Jennifer; Rose, Michelle; Moore, Gregory J.; Rosenberg, David R.

    2004-01-01

    Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). Method: Single-voxel proton magnetic resonance spectroscopic ([.sup.1]H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naive children and adolescents with MDD…

  20. Selective Neurocognitive Impairments in Adolescents with Major Depressive Disorder

    ERIC Educational Resources Information Center

    Han, Georges; Klimes-Dougan, Bonnie; Jepsen, Susie; Ballard, Kristin; Nelson, Megan; Houri, Alaa; Kumra, Sanjiv; Cullen, Kathryn

    2012-01-01

    This study investigated whether major depression in adolescence is characterized by neurocognitive deficits in attention, affective decision making, and cognitive control of emotion processing. Neuropsychological tests including the Wechsler Abbreviated Scale of Intelligence, the Continuous Performance Test-Identical Pairs, the Attention Network…

  1. Abnormal Temporal Difference Reward-Learning Signals in Major Depression

    ERIC Educational Resources Information Center

    Kumar, P.; Waiter, G.; Ahearn, T.; Milders, M.; Reid, I.; Steele, J. D.

    2008-01-01

    Anhedonia is a core symptom of major depressive disorder (MDD), long thought to be associated with reduced dopaminergic function. However, most antidepressants do not act directly on the dopamine system and all antidepressants have a delayed full therapeutic effect. Recently, it has been proposed that antidepressants fail to alter dopamine…

  2. Processing of facial emotion expression in major depression: a review.

    PubMed

    Bourke, Cecilia; Douglas, Katie; Porter, Richard

    2010-08-01

    Processing of facial expressions of emotion is central to human interaction, and has important effects on behaviour and affective state. A range of methods and paradigms have been used to investigate various aspects of abnormal processing of facial expressions in major depression, including emotion specific deficits in recognition accuracy, response biases and attentional biases. The aim of this review is to examine and interpret data from studies of facial emotion processing in major depression, in the context of current knowledge about the neural correlates of facial expression processing of primary emotions. The review also discusses the methodologies used to examine facial expression processing. Studies of facial emotion processing and facial emotion recognition were identified up to December 2009 utilizing MEDLINE and Web of Science. Although methodological variations complicate interpretation of findings, there is reasonably consistent evidence of a negative response bias towards sadness in individuals with major depression, so that positive (happy), neutral or ambiguous facial expressions tend to be evaluated as more sad or less happy compared with healthy control groups. There is also evidence of increased vigilance and selective attention towards sad expressions and away from happy expressions, but less evidence of reduced general or emotion-specific recognition accuracy. Data is complicated by the use of multiple paradigms and the heterogeneity of major depression. Future studies should address methodological problems, including variations in patient characteristics, testing paradigms and procedures, and statistical methods used to analyse findings.

  3. Consumers with Major Depressive Disorder: Factors Influencing Job Placement

    ERIC Educational Resources Information Center

    Hergenrather, Kenneth C.; Haase, Eileen; Zeglin, Robert J.; Rhodes, Scott D.

    2013-01-01

    The theory of planned behavior (TPB) was applied to study the factors that influence the intention of public rehabilitation placement professionals to place consumers with major depressive disorder (MDD) in jobs. A sample of 108 public rehabilitation placement professionals in the Mid-Atlantic region of the United States completed the MDD…

  4. Sertraline in Children and Adolescents with Major Depressive Disorder

    ERIC Educational Resources Information Center

    Donnelly, Craig L.; Wagner, Karen Dineen; Rynn, Moira; Ambrosini, Paul; Landau, Phyllis; Yang, Ruoyong; Wohlberg, Christopher J.

    2006-01-01

    Objective: To explore time to first response and time to first persistent response of sertraline versus placebo and compare these parameters between children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199) with major depressive disorder. Method: A 10-week placebo-controlled treatment was followed by a 24-week open-label…

  5. Voice Acoustical Measurement of the Severity of Major Depression

    ERIC Educational Resources Information Center

    Cannizzaro, Michael; Harel, Brian; Reilly, Nicole; Chappell, Phillip; Snyder, Peter J.

    2004-01-01

    A number of empirical studies have documented the relationship between quantifiable and objective acoustical measures of voice and speech, and clinical subjective ratings of severity of Major Depression. To further explore this relationship, speech samples were extracted from videotape recordings of structured interviews made during the…

  6. Interpersonal Pathoplasticity in the Course of Major Depression

    ERIC Educational Resources Information Center

    Cain, Nicole M.; Ansell, Emily B.; Wright, Aidan G. C.; Hopwood, Christopher J.; Thomas, Katherine M.; Pinto, Anthony; Markowitz, John C.; Sanislow, Charles A.; Zanarini, Mary C.; Shea, M. Tracie; Morey, Leslie C.; McGlashan, Thomas H.; Skodol, Andrew E.; Grilo, Carlos M.

    2012-01-01

    Objective: The identification of reliable predictors of course in major depressive disorder (MDD) has been difficult. Evidence suggests that the co-occurrence of personality pathology is associated with longer time to MDD remission. Interpersonal pathoplasticity, the mutually influencing nonetiological relationship between psychopathology and…

  7. Major depressive disorder symptoms in male and female young adults.

    PubMed

    Lopez Molina, Mariane Acosta; Jansen, Karen; Drews, Cláudio; Pinheiro, Ricardo; Silva, Ricardo; Souza, Luciano

    2014-01-01

    This research aimed to compare the prevalence rates of major depressive disorder (MDD) and to differentiate the presence and severity of depressive symptoms between women and men aged 18-24 years. In this population-based, cross-sectional study (n = 1560), young adults were screened with the Mini International Neuropsychiatric Interview for MDD (n = 137). Participants then completed a self-report questionnaire to gather sociodemographic data, and the presence of each symptom of depression was assessed with the Beck Depression Inventory. The proportion of women (12.2%) with MDD was higher than that of men (5.3%). The symptoms of depression found to be significantly more prevalent in women were sadness, crying, difficulty making decisions, and lack of energy, as well as self-criticism, irritability, changes in self-image, work difficulty, and loss of interest in sex. Sadness and self-criticism were significantly more severe in women than in men. The presentation of depressive symptoms in young adults with MDD differed between men and women.

  8. Phonologically-based biomarkers for major depressive disorder

    NASA Astrophysics Data System (ADS)

    Trevino, Andrea Carolina; Quatieri, Thomas Francis; Malyska, Nicolas

    2011-12-01

    Of increasing importance in the civilian and military population is the recognition of major depressive disorder at its earliest stages and intervention before the onset of severe symptoms. Toward the goal of more effective monitoring of depression severity, we introduce vocal biomarkers that are derived automatically from phonologically-based measures of speech rate. To assess our measures, we use a 35-speaker free-response speech database of subjects treated for depression over a 6-week duration. We find that dissecting average measures of speech rate into phone-specific characteristics and, in particular, combined phone-duration measures uncovers stronger relationships between speech rate and depression severity than global measures previously reported for a speech-rate biomarker. Results of this study are supported by correlation of our measures with depression severity and classification of depression state with these vocal measures. Our approach provides a general framework for analyzing individual symptom categories through phonological units, and supports the premise that speaking rate can be an indicator of psychomotor retardation severity.

  9. Levomilnacipran for the treatment of major depressive disorder: a review.

    PubMed

    Asnis, Gregory M; Henderson, Margaret A

    2015-01-01

    Levomilnacipran (LVM, Fetzima(®)) was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. It is a unique dual neurotransmitter reuptake inhibitor. In contrast with other selective serotonin norepinephrine reuptake inhibitors, including duloxetine, venlafaxine, and desvenlafaxine, it has greater selectivity for inhibiting norepinephrine reuptake than serotonin reuptake. Our review focuses on the efficacy, safety, and tolerability data for five double-blind, placebo-controlled, short-term studies and two long-term studies. In the short-term studies, LVM was found to be more effective than placebo in reducing depression (Montgomery-Åsberg Depression Rating Scale) scores as well as improving functional impairment (Sheehan Disability Scale) scores. Long-term studies found LVM to be similarly effective but in the only placebo-controlled long-term study, LVM was not significantly superior to placebo. LVM is fairly well tolerated, with the most common adverse events being nausea, headache, dry mouth, hyperhidrosis, and constipation. Discontinuation rates were mildly increased in those being treated with LVM (9%) versus placebo (3%). Adverse events were not dose-related except for urinary hesitancy and erectile dysfunction. LVM was weight neutral, was not toxic to the liver, and did not cause clinically significant QTc prolongation. Consistent with being a predominant potentiator of norepinephrine, pulse and blood pressure were significantly elevated by LVM but rarely induced tachycardia or hypertension. LVM is a relatively safe alternative antidepressant treatment with minimal drug-drug interactions. It is the only antidepressant that has in its labeling that it is not only effective in improving depression but also effective in improving impaired functioning. Whether this important effect on functioning is unique to LVM must be researched. In addition, whether LVM might be effective in norepinephrine

  10. Improvement of major depression is associated with increased erythrocyte DHA.

    PubMed

    Meyer, Barbara J; Grenyer, Brin F S; Crowe, Trevor; Owen, Alice J; Grigonis-Deane, Elizabeth M; Howe, Peter R C

    2013-09-01

    The aim of this study was to determine if changes in omega-3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression. A total of 95 volunteers receiving treatment for major depression were randomised to consume 8 × 1 g capsules per day of HiDHA (2 g DHA, 0.6 g EPA and 10 mg Vitamin E) or olive oil (placebo) for 16 weeks, whilst undergoing weekly counseling sessions by trained clinical psychologists using a standard empirically validated psychotherapy. Depression status was assessed using the 17 item Hamilton rating scale for depression and the Beck Depression Inventory by a psychodiagnostician who was blind to the treatment. Blood was taken at baseline and 16 weeks (n = 48) for measurement of erythrocyte fatty acids. With HiDHA supplementation, erythrocyte DHA content rose from 4.1 ± 0.2 to 7.9 ± 0.4 % (mean ± SEM, p < 0.001) of total fatty acids but did not change (4.0 ± 0.2 to 4.1 ± 0.2 %) in the olive oil group. The mean changes in scores of depression did not differ significantly between the two groups (-12.2 ± 2.1 for tuna oil and -14.4 ± 2.3 for olive oil). However, analysis of covariance showed that in the fish oil group there was a significant correlation (r = -0.51) between the change in erythrocyte DHA and the change in scores of depression (p < 0.05). Further study of the relationship between DHA and depression is warranted.

  11. TERT Core Promotor Mutations in Early-Onset Bladder Cancer

    PubMed Central

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  12. Extended-release Trazodone in Major Depressive Disorder

    PubMed Central

    Sheehan, David V.; Croft, Harry A.; Levitt, Randy J.; Brullé, Claire; Bouchard, Sylvie; Rozova, Anna

    2009-01-01

    Objective: To investigate the efficacy, safety, and clinical benefit of a once-daily formulation of trazodone (Trazodone Contramid® OAD) in the treatment of major depressive disorder. Design/Participants: In this double-blind study, 412 patients with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) were randomized 1:1 to receive either Trazodone Contramid OAD (150 to 375mg) or placebo. Treatment was titrated over two weeks to each individual optimal dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability. Measurements: The primary end point was change in the 17-item Hamilton Depression Rating Scale total score from baseline to last study visit. Secondary end points included Hamilton Depression Rating Scale responders/remitters, change in Montgomery-Åsberg Depression Rating Scale, Clinician and Patient Global Improvement Scales, and quality of sleep. Results: From the end of titration to the end of the six-week treatment period, the mean maximum daily dose of the intent-to-treat population was 310mg for the active group and 355mg for the placebo group. There was a statistically significant difference between trazodone and placebo on the mean HAMD-17 score (-11.4 vs. -9.3, P=0.012). A significant difference was present as early as Week 1 and was maintained at all subsequent study visits. Many secondary end points supported these findings, including improvements in quality of sleep. The most frequent adverse events were the same for both the treatment and placebo groups: headache and somnolence. There were no serious adverse events that were considered related to treatment. There were no clinically significant electrocardiogram or laboratory abnormalities. Conclusions: The trazodone Contramid formulation was more effective than placebo in major depressive disorder and was well tolerated. PMID:19724732

  13. The expression of depression among Javanese patients with major depressive disorder: a concept mapping study.

    PubMed

    Brintnell, E Sharon; Sommer, Ryan W; Kuncoro, Bambang; Setiawan, G Pandu; Bailey, Patricia

    2013-08-01

    In this study, we explored the presentation of clinical depression in Java, Indonesia. Interviews were conducted with 20 Javanese patients (male and female) with major depressive disorder from both lower and higher socioeconomic levels. The recruited participants came from provincial and private mental health hospitals in the cities of Solo, Yogykarta (Jogja), Jakarta, and Malang on the island of Java, Indonesia. Concept mapping methodology using multidimensional scaling and hierarchical cluster analysis was used to identify underlying themes in the expression of depressive phenomena in this Indonesian population. The results identified themes that grouped into six clusters: interpersonal relationships, hopelessness, physical/somatic, poverty of thought, discourage, and defeat. Findings give support to the view that culture influences the expression of Indonesian depressive phenomenology, which nevertheless has some common roots with Western clinical pictures of the disorder. Cultural influences may mask symptoms of the disorder to clinicians. Diagnostic and assessment tools must be carefully selected to ensure they address culturally specific expressions of depression.

  14. Early Onset of Sexual Intercourse and Parental Incarceration among African American Youth Living in Urban Public Housing.

    PubMed

    Nebbitt, Von E; Voisin, Dexter R; Tirmazi, M Taqi

    2017-02-01

    Mass incarceration, substance use, and adolescent early onset of sex (e.g., initiate sexual intercourse at 13 years of age or younger) are social problems with disparate impacts on low-income African American communities. Two out of every five inmates in state and federal prisons are African American and the vast majority of these inmates are from low-income communities. Furthermore, this population experiences more severe consequences of substance use and abuse compared to other populations. In sum, African American youth endure the lion share of problems that mass incarceration and substance use leave in their wake. It is likely that the early onset of sex reported by African American youth in national data is related to mass incarceration and substance use in their communities. Using a sample of 142 African American youth, this paper assesses whether parental incarceration or substance, or both, are related to the likelihood of early onset of sex. Analytic procedures included chi-square and sequential logistic regression. The sample reported a mean age of 19 and 36% reported early onset of sex. Being male, paternal incarcerated, and maternal alcohol problems were associated with an increased likelihood of early onset of sex. Results point to a need for supportive services for the children of incarcerated parents, particularly those living in urban public housing developments.

  15. Dynamics of behavioral organization and its alteration in major depression

    NASA Astrophysics Data System (ADS)

    Nakamura, Toru; Kiyono, Ken; Yoshiuchi, Kazuhiro; Nakahara, Rika; Struzik, Zbigniew R.; Yamamoto, Yoshiharu

    2007-07-01

    We describe the nature of human behavioral organization, specifically how resting and active periods are interwoven throughout daily life. Active period durations with physical activity counts successively above a predefined threshold follow a stretched exponential (gamma-type) cumulative distribution with characteristic time, both in healthy individuals and in patients with major depressive disorder. On the contrary, resting period durations below the threshold for both groups obey a scale free power law cumulative distribution over two decades, with significantly lower scaling exponents in the patients. We thus find underlying robust laws governing human behavioral organization, with a parameter altered in depression.

  16. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  17. Differences in depressive symptoms between Korean and American outpatients with major depressive disorder.

    PubMed

    Jeon, Hong Jin; Walker, Rosemary S; Inamori, Aya; Hong, Jin Pyo; Cho, Maeng Je; Baer, Lee; Clain, Alisabet; Fava, Maurizio; Mischoulon, David

    2014-05-01

    Previous epidemiologic studies have revealed that East-Asian populations experience fewer depressive symptoms than American populations do. However, it is unclear whether this difference applies to clinical patients with major depressive disorder (MDD). This present study included 1592 Korean and 3744 American outpatients who were 18 years of age or older and met the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for single or recurrent episodes of nonpsychotic MDD, and evaluated their symptoms of depression using the Hamilton Depression Rating Scale and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form. Korean patients scored significantly lower for guilt and depressed mood items, and higher for hypochondriasis and suicidality items than American patients did, after adjusting for total Hamilton Depression Rating Scale scores. Conversely, no significant differences were found in quality and function of daily life between groups. Multivariate logistic regression analyses revealed that Korean patients experienced less frequent depressed mood and guilt, including verbal and nonverbal expression of depressed mood [adjusted odds ratio (AOR) = 0.14, 95% confidence interval (CI) 0.08-0.23] and feelings of punishment (AOR = 0.036, 95% CI 0.025-0.054) when compared with Americans after adjusting for age and sex. Conversely, Korean patients experienced more frequent suicidality and hypochondriasis, including suicidal ideas or gestures (AOR = 2.10, 95% CI 1.60-2.76) and self-absorption of hypochondriasis (AOR = 1.94, 95% CI 1.70-2.20). In conclusion, decreased expression of depressed mood and guilt may cause underdiagnosis of MDD in Korean patients. Early diagnosis of and intervention for depression and suicide may be delayed because of this specific cross-cultural difference in depression symptoms.

  18. Psychosocial and neurocognitive profiles in depressed patients with major depressive disorder and bipolar disorder.

    PubMed

    Godard, Julie; Grondin, Simon; Baruch, Philippe; Lafleur, Martin F

    2011-12-30

    Previous studies have revealed psychosocial and cognitive impairments in patients during depression. The primary aim of this study was to investigate whether patients with major depression (MDD) and bipolar disorder (BD) differ in psychosocial and neurocognitive profiles. A second aim was to examine whether cognitive impairments are homogeneous among depressed patients. Patients with MDD (n=16) and BD (n=14) were enrolled during a major depressive episode. About half of them had comorbidities, including personality, substance use, and anxiety disorders. Information was collected about symptomatology and psychosocial functioning, whereas an exhaustive neuropsychological battery was administered to assess cognition. During a depressive episode, MDD and BD patients had global psychosocial dysfunction, characterized by occupational and relational impairments. A cognitive slowing was also observed, as well as deficits related to alertness, spontaneous flexibility, sustained and divided attention. Moreover, severity of depression and cognitive functions were significantly associated with psychosocial functioning. In the case of severe mood disorders, psychosocial and neurocognitive functioning seem similar among MDD and BD patients during a depressive episode. In addition to an altered daily functioning, the neurocognitive profile was heterogeneous with regard to the nature and extent of cognitive deficits. Executive functions, as well as verbal learning and memory, were preserved better than attentional processes.

  19. Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder

    PubMed Central

    Baek, Ji Hyun; Kim, Hee-Jin; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Nierenberg, Andrew; Heo, Jung-Yoon

    2016-01-01

    Objective Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD). Methods A total of 709 patients who were newly diagnosed with MDD were recruited. Anxiety levels of participants were evaluated using the Anxiety/ Somatization subitem of the Hamilton Depression Rating Scale. The association between WBC subset fraction and anxiety was evaluated. Results Basophil and eosinophil sub-fractions showed significant negative correlations with HAM-D anxiety/somatization factor scores (basophils: r=-0.092, p=0.014 and eosinophils: r=-0.075, p=0.046). When an anxiety score (a sum of somatic and psychic anxiety) was entered as a dependent variable, only basophils showed significant negative association with the anxiety scores after adjusting for all other WBC subset counts and demographic factors (t=-2.57, p=0.010). Conclusion This study showed that anxious depression had a decreased basophil subfraction, which might be associated with involvement of inflammation in development of anxious depression. PMID:27247599

  20. Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

    PubMed

    Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

    2017-01-01

    Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients.

  1. Vortioxetine for the treatment of major depressive disorder.

    PubMed

    Tritschler, Laurent; Felice, Daniela; Colle, Romain; Guilloux, Jean-Philippe; Corruble, Emmanuelle; Gardier, Alain Michel; David, Denis Joseph

    2014-11-01

    Vortioxetine (Brintellix(®), 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a multimodal antidepressant targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin (5-HT) transporter (5-HTT). Vortioxetine administration induces antidepressant- and anxiolytic-like effects, and can enhance cognitive performance in rodents. Several clinical trials have reported the efficiency and a satisfactory tolerability of vortioxetine treatment in depressed patients. Remarkably, vortioxetine has a specific positive impact on cognitive symptoms in depressed patients. Overall, vortioxetine is an efficacious antidepressant drug for the treatment of patients with a major depressive episode and has a unique mechanism of action offering a new therapeutic option.

  2. Cognitive control adjustments and conflict adaptation in major depressive disorder.

    PubMed

    Clawson, Ann; Clayson, Peter E; Larson, Michael J

    2013-08-01

    Individuals with major depressive disorder (MDD) show alterations in the cognitive control function of conflict processing. We examined the influence of these deficits on behavioral and event-related potential (ERP) indices of conflict adaptation, a cognitive control process wherein previous-trial congruency modulates current-trial performance, in 55 individuals with MDD and 55 matched controls. ERPs were calculated while participants completed a modified flanker task. There were nonsignificant between-groups differences in response time, error rate, and N2 indices of conflict adaptation. Higher depressive symptom scores were associated with smaller mean N2 conflict adaptation scores for individuals with MDD and when collapsed across groups. Results were consistent when comorbidity and medications were analyzed. These findings suggest N2 conflict adaptation is associated with depressive symptoms rather than clinical diagnosis alone.

  3. Imaging genetics studies on monoaminergic genes in major depressive disorder.

    PubMed

    Won, Eunsoo; Ham, Byung-Joo

    2016-01-04

    Although depression is the leading cause of disability worldwide, current understanding of the neurobiology of depression has failed to be translated into clinical practice. Major depressive disorder (MDD) pathogenesis is considered to be significantly influenced by multiple risk genes, however genetic effects are not simply expressed at a behavioral level. Therefore the concept of endophenotype has been applied in psychiatric genetics. Imaging genetics applies anatomical or functional imaging technologies as phenotypic assays to evaluate genetic variation and their impact on behavior. This paper attempts to provide a comprehensive review of available imaging genetics studies, including reports on genetic variants that have most frequently been linked to MDD, such as the monoaminergic genes (serotonin transporter gene, monoamine oxidase A gene, tryptophan hydroxylase-2 gene, serotonin receptor 1A gene and catechol-O-methyl transferase gene), with regard to key structures involved in emotion processing, such as the hippocampus, amygdala, anterior cingulate cortex and orbitofrontal cortex.

  4. Feeling blue or turquoise? Emotional differentiation in major depressive disorder.

    PubMed

    Demiralp, Emre; Thompson, Renee J; Mata, Jutta; Jaeggi, Susanne M; Buschkuehl, Martin; Barrett, Lisa Feldman; Ellsworth, Phoebe C; Demiralp, Metin; Hernandez-Garcia, Luis; Deldin, Patricia J; Gotlib, Ian H; Jonides, John

    2012-01-01

    Some individuals have very specific and differentiated emotional experiences, such as anger, shame, excitement, and happiness, whereas others have more general affective experiences of pleasure or discomfort that are not as highly differentiated. Considering that individuals with major depressive disorder (MDD) have cognitive deficits for negative information, we predicted that people with MDD would have less differentiated negative emotional experiences than would healthy people. To test this hypothesis, we assessed participants' emotional experiences using a 7-day experience-sampling protocol. Depression was assessed using structured clinical interviews and the Beck Depression Inventory-II. As predicted, individuals with MDD had less differentiated emotional experiences than did healthy participants, but only for negative emotions. These differences were above and beyond the effects of emotional intensity and variability.

  5. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    PubMed

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy.

  6. Inflammation profile of four early onset Crohn patients.

    PubMed

    Marcuzzi, Annalisa; Girardelli, Martina; Bianco, Anna Monica; Martelossi, Stefano; Magnolato, Andrea; Tommasini, Alberto; Crovella, Sergio

    2012-02-10

    Crohn disease (CD) is a multifactorial disorder affecting mainly young adults. Sometimes, however, it can present in the first year of life (Early onset Crohn disease (EOCD)) showing an unpredictable course and can often be more severe than at older ages. Some cases have been associated to an underlying primary immunodeficiency such as IL10R deficiency. We studied the functional response to IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn-like colitis. We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. Further studies to determine its pathogenic effect should be performed. In addition IL-10 mediated inhibition of LPS-induced TNFα expression was measured in patient's monocytes.

  7. A Review of Vilazodone, Serotonin, and Major Depressive Disorder

    PubMed Central

    Thase, Michael E.

    2014-01-01

    Objective: To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A) autoreceptors, which are proposed to be involved in delaying therapeutic efficacy. Vilazodone was specifically designed to function both as an SSRI and a partial agonist at 5-HT1A receptors. This combined mechanism is proposed to decrease time to efficacy, minimize sexual side effects, and provide concomitant anxiolytic properties. Data Sources: A PubMed search of all English-language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A, depression and buspirone, depression and pindolol, and vilazodone. Study Selection: We found 47 articles and abstracts that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol, buspirone, and vilazodone in depression. Data Extraction: This review summarizes current literature involving antidepressant activity, the role of 5-HT1A autoreceptors, and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists, with a focus on vilazodone. Results:Vilazodone has demonstrated efficacy in 2 large, randomized, double-blind, placebo-controlled trials in major depressive disorder. Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety. A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy. Conclusions: If future studies corroborate the clinical benefits attributed to its mechanism of action, vilazodone may show potential advantages in terms of onset of action, sexual side effects, and anxiolytic activity in patients with major depressive disorder. PMID:24940527

  8. Early onset neonatal sepsis: diagnostic dilemmas and practical management.

    PubMed

    Bedford Russell, A R; Kumar, R

    2015-07-01

    Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms.

  9. Early onset marfan syndrome: Atypical clinical presentation of two cases

    PubMed Central

    Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

    2015-01-01

    Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

  10. Blood-Based Biomarkers of Early-Onset Breast Cancer

    DTIC Science & Technology

    2014-10-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Women with early-onset breast cancer are thought to have a higher contribution of inherited ...risk than those forming sporadic cancers at later ages. This inherited susceptibility to breast cancer might manifest as differences in gene...expression patterns within key oncogenic pathways. While the normal breast is the ideal tissue in which to study this phenomenon, gene expression profiling

  11. St John's wort (Hypericum perforatum) in major depression.

    PubMed

    Shelton, Richard C

    2009-01-01

    The herb St John's wort (Hypericum perforatum) has been used for centuries to treat a variety of medical illnesses. In certain areas of Europe, St John's wort has been a commonly prescribed treatment for depression, but, in the United States, it is available for purchase over the counter as an herbal supplement. Some researchers believe that specific chemical constituents of St John's wort produce change in depression in a way similar to that of antidepressant medications, yet this hypothesis is problematic. In addition, studies that support the efficacy of St John's wort in patients with mild-to-moderate depression have limitations that may affect the accuracy of their conclusions. Studies measuring the effect of St John's wort in major depression have reported conflicting results and need to be reexamined. Because St John's wort is considered by some to be an alternative to conventional therapies, clinicians need to know whether it is an effective and safe treatment for different levels of severity of depression. Current evidence does not support its use, and, because of potential drug interactions, St John's wort is not a benign treatment.

  12. Unintentional Injuries among Psychiatric Outpatients with Major Depressive Disorder

    PubMed Central

    Hung, Ching-I; Liu, Chia-Yih; Yang, Ching-Hui

    2016-01-01

    Background No study has investigated the percentages of and factors related to unintentional injuries among psychiatric outpatients with major depressive disorder (MDD). This study aimed to investigate these issues. Methods One-hundred and forty-one outpatients with MDD at baseline were enrolled from psychiatric outpatients by systematic sampling, and 119 subjects attended a one-year follow-up. Self-reported unintentional injuries in the past one year were recorded. Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The severity of depression was evaluated by the Hamilton Depression Rating Scale. Other data, including body weight and height, cigarette smoking, headaches, and medications, were collected. Generalized Estimating Equations were used to investigate independent factors related to unintentional injuries. Results At baseline and follow-up, 40.4% and 27.7% of subjects had experienced at least one unintentional injury in the past one year, respectively. About half of subjects with unintentional injuries needed medical treatment for injuries and had functional impairment due to injuries. A greater severity of depression, cigarette smoking, a higher body mass index, and an older age were independent risk factors related to unintentional injuries. Conclusion Unintentional injuries that increased the medical burden and functional impairment were common among outpatients with MDD and should not be neglected. Treatment of depression, control of body weight, and quitting cigarettes might be helpful to prevent unintentional injuries. PMID:27992483

  13. RSA Reactivity in Current and Remitted Major Depressive Disorder

    PubMed Central

    Bylsma, Lauren M.; Salomon, Kristen; Taylor-Clift, April; Morris, Bethany H.; Rottenberg, Jonathan

    2014-01-01

    Objective Low resting respiratory sinus arrhythmia (RSA) levels and blunted RSA reactivity are thought to index impaired emotion regulation capacity. Major Depressive Disorder (MDD) has been associated with abberant RSA reactivity and recovery to a speech stressor task relative to healthy controls. Whether impaired RSA functioning reflects aspects of the depressed mood state or a stable vulnerability marker for depression is unknown. Methods We compared resting RSA and RSA reactivity between individuals with MDD (n=49), remitted depression (RMD, n=24), and healthy controls (n=45). ECG data were collected during a resting baseline, a paced-breathing baseline, and two reactivity tasks (speech stressor, cold exposure). Results A group by time quadratic effect emerged (F=4.36(2,109), p=.015) for RSA across phases of the speech stressor (baseline, instruction, preparation, speech, recovery). Follow-up analyses revealed that those with MDD uniquely exhibited blunted RSA reactivity, whereas RMD and controls both exhibited normal task-related vagal withdrawal and post-task recovery. The group by time interaction remained after covariation for age, sex, waist circumference, physical activity, and respiration, but not sleep quality. Conclusions These results provide new evidence that abberant RSA reactivity marks features that track the depressed state, such as poor sleep, rather than a stable trait evident among asymtomatic persons. PMID:24367127

  14. Altered fecal microbiota composition in patients with major depressive disorder.

    PubMed

    Jiang, Haiyin; Ling, Zongxin; Zhang, Yonghua; Mao, Hongjin; Ma, Zhanping; Yin, Yan; Wang, Weihong; Tang, Wenxin; Tan, Zhonglin; Shi, Jianfei; Li, Lanjuan; Ruan, Bing

    2015-08-01

    Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

  15. Executive Attention Impairment in Adolescents with Major Depressive Disorder

    PubMed Central

    Sommerfeldt, Sasha L.; Cullen, Kathryn R.; Han, Georges; Fryza, Brandon J.; Houri, Alaa K.; Klimes-Dougan, Bonnie

    2015-01-01

    Objective Neural network models that guide neuropsychological assessment practices are increasingly used to explicate depression, though a paucity of work has focused on regulatory systems that are under development in adolescence. The purpose of this study was to evaluate subsystems of attention related to executive functioning including alerting, orienting, and executive attention networks, as well as sustained attention with varying working memory load, in a sample of depressed and well adolescents. Method Neuropsychological functioning in 99 adolescents diagnosed with major depressive disorder (MDD) and 63 adolescent healthy controls (M = 16.6 years old) was assessed on the Attention Network Task (ANT) and the Continuous Performance Test, Identical Pairs (CPT). Results Adolescents with MDD, particularly those who were not medicated, were slower to process conflict (slower reaction time on the executive attention scale of the ANT) compared to controls, particularly for those who were not undergoing psychopharmacological treatment. Tentative evidence also suggests that within the MDD group, orienting performance was more impaired in those with a history of comorbid substance use disorder, and alerting was more impaired in those with a history of a suicide attempt. Conclusions Adolescents with depression showed impaired executive attention, although cognitive performance varied across subgroups of patients. These findings highlight the importance of examining neurocognitive correlates associated with features of depression and suggest an avenue for future research to help guide the development of interventions. PMID:26566871

  16. Gene Expression Analysis of Sporadic Early-Onset Rectal Adenocarcinoma

    PubMed Central

    Nfonsam, V; Xu, W; Koblinski, J; Jandova, J

    2016-01-01

    Background Overall declines in incidence of rectal cancer (RC) in patients older than 50 years have been mostly attributed to improvement in treatment modalities and introduction of age-based screening. Recent studies, however, have shown a rise in the incidence of RC in patients younger than 50 years. The etiology of early-onset (EO) RC is not well understood. The aim of this study is to elucidate the molecular features of (EO) RC and show its uniqueness compared to late-onset (LO) disease. Methods Two cohorts of patients with sporadic RC were identified. Tumors and matching non-involved tissues from six (EO) RC patients (< 50 years) and six (LO) RC patients (>65 years) were obtained from Pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of 770 cancer related genes representing 13 canonical pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05. Results When we compared rectal tumors to non-involved rectal tissues, changes in expression levels of 171 genes were statistically significant in early-onset group and 151 genes in late-onset group. Further comparative gene expression analysis between early- and late-onset rectal tumors normalized to their matching non-involved tissues revealed that changes in expression of 65 genes were unique to early-onset rectal tumors with 16 genes being up- and 49 genes down-regulated using the cutoff criteria of expression levels difference >2 fold and p-value <0.01. At the pathway level, MAPK signaling was the most deregulated pathway in early-onset rectal tumors compared to PI3K-AKT signaling pathway being the most deregulated in late-onset rectal tumors. Conclusions Results of

  17. The inflammatory cytokines: molecular biomarkers for major depressive disorder?

    PubMed

    Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

    2015-01-01

    Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

  18. The Role of Lipid Biomarkers in Major Depression

    PubMed Central

    Parekh, Amy; Smeeth, Demelza; Milner, Yasmin; Thuret, Sandrine

    2017-01-01

    In the UK, the lifetime-documented prevalence of major depressive disorder (MDD) is currently 10%. Despite its increasing prevalence and devastating impact on quality of life, the pathophysiological mechanisms underpinning MDD remain to be fully elucidated. Current theories of neurobiological components remain incomplete and protein-centric, rendering pharmacological treatment options suboptimal. In this review, we highlight the pivotal role of lipids in intra- and inter-neuronal functioning, emphasising the potential use of lipids as biomarkers for MDD. The latter has significant implications for improving our understanding of MDD at the cellular and circuit level. There is particular focus on cholesterol (high and low density lipoprotein), omega-3, and omega-6 polyunsaturated fatty acids due to established evidence in the literature of a link between atherosclerotic disease and major depression. We argue that there is significant potential scope for the use of such peripheral biomarkers in the diagnosis, stratification and treatment of MDD. PMID:28165367

  19. [Bipolarity correlated factors in major depression: about 155 Tunisian inpatients].

    PubMed

    Gassab, L; Mechri, A; Gaha, L; Khiari, G; Zaafrane, F; Zougaghi, L

    2002-01-01

    The distinction between the depressive troubles according to their inclusion in bipolar disorders or in recurrent depressive disorders offers an evident practical interest. In fact, the curative and mainly the preventive treatment of these troubles are different. So it is necessary to identify the predictive factors of bipolar development in case of inaugural depressive episode. In 1983, Akiskal was the first who identified those factors: pharmacological hypomania, puerperal depression, onset at early age (<25 years), presence of psychotic characteristics, hypersomnia and psychomotor inhibition. Through this study, the authors try to compare the epidemiological, clinical and evolution characteristics of major depression in bipolar disorders to recurrent depressive disorders in order to indicate the correlated factors with bipolarity. It is a retrospective and comparative study based on about 155 inpatients for major depressive episode during the period between January 1994 and December 1998. These patients were divided into two groups according the DSM IV criteria: bipolar group (96 patients) and recurrent depressive group (59 patients). Both groups were compared according to socio-demographic data, life events in childhood, personal and family history, clinical and evolution characteristics of the index depressive episode. The predictive factors proposed by Akiskal were systematically examined. It was found out that the following factors were correlated with bipolarity: high rate of separation and divorce (17.7% versus 5.1%; p=0.02), family history of psychiatric disorders (56.3% versus 35.6%; p=0.012) especially bipolar ones (29.2% versus 3.4%; p=0,00008), onset at early age (mean age of onset: 24.8 8.2 years versus 34.1 12.6 years; p=0.000004), number of affective episode significantly more frequent (mean 3.6 versus 2.5; p=0.03), sudden onset of depressive episode (44.8% versus 15.9%; p=0.0003) and presence of psychotic characteristics (69.8% versus 16.7%; p=0

  20. Quality of depression treatment in Black Americans with major depression and comorbid medical illness

    PubMed Central

    Agyemang, Amma A.; Mezuk, Briana; Perrin, Paul; Rybarczyk, Bruce

    2014-01-01

    Objective To evaluate how comorbid type 2 diabetes (T2DM) and hypertension (HT) influence depression treatment and to assess whether these effects operate differently in a nationally-representative community-based sample of Black Americans. Methods Data came from the National Survey of American Life (N=3,673), and analysis is limited to respondents who met lifetime criteria for major depression (MD) (N=402). Depression care was defined according to American Psychiatric Association (APA) guidelines and included psychotherapy, pharmacotherapy, and satisfaction with services. Logistic regression was used to examine the effects of T2DM and HT on quality of depression care. Results Only 19.2% of Black Americans with MD alone, 7.8% with comorbid T2DM, and 22.3% with comorbid HT reported APA guideline-concordant psychotherapy or antidepressant treatment. Compared to respondents with MD alone, respondents with MD + T2DM/HT were no more or less likely to receive depression care. Respondents with MD + HT + T2DM were more likely to report any guideline-concordant care (OR=3.32 95% CI [1.07, 10.31]). Conclusions Although individuals with MD and comorbid T2DM + HT were more likely to receive depression care, guideline-concordant depression care is low among Black Americans, including those with comorbid medical conditions. PMID:24793895

  1. Early parental loss and depression history: associations with recent life stress in major depressive disorder.

    PubMed

    Slavich, George M; Monroe, Scott M; Gotlib, Ian H

    2011-09-01

    Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss.

  2. [THE THERAPUETIC USE OF TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION].

    PubMed

    Németh, Viola Luca; Csifcsák, Gábor; Kincses, Zsigmond Tamás; Janka, Zoltán; Must, Anita

    2016-03-30

    The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention.

  3. Serotonin receptors in suicide victims with major depression.

    PubMed

    Stockmeier, C A; Dilley, G E; Shapiro, L A; Overholser, J C; Thompson, P A; Meltzer, H Y

    1997-02-01

    Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. Brain samples were collected at autopsy from suicide victims with a current episode of major depression and matched comparison subjects who died of natural or accidental causes. Retrospective psychiatric assessments were collected from knowledgeable informants for all suicide victims and most of the comparison subjects. Psychiatric diagnoses were determined according to DSM-III-R criteria. Any subjects with current psychoactive substance use disorders were excluded. Quantitative receptor autoradiography was used in serial sections of the right prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8-hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare control subjects and suicide victims with major depression. The age of subjects, the time from death to freezing the tissue (postmortem interval), and the storage time of tissues in the freezer were used as covariates in the analyses. There were no significant differences between suicide victims with major depression and comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right prefrontal cortex or the hippocampus. The current results suggest that the number of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or hippocampus are not different in suicide victims with major depression.

  4. Novel glutamatergic agents for major depressive disorder and bipolar disorder

    PubMed Central

    Machado-Vieira, Rodrigo; Ibrahim, Lobna; Henter, Ioline D.; Zarate, Carlos A.

    2011-01-01

    Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) are common, chronic, recurrent mental illnesses that affect the lives and functioning of millions of individuals worldwide. Growing evidence suggests that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of mood disorders as well as the efficacy of glutamatergic agents as novel therapeutics. PMID:21971560

  5. Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

    PubMed

    Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

    2016-08-01

    Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise.

  6. St. John's Wort for Major Depressive Disorder: A Systematic Review.

    PubMed

    Maher, Alicia Ruelaz; Hempel, Susanne; Apaydin, Eric; Shanman, Roberta M; Booth, Marika; Miles, Jeremy N V; Sorbero, Melony E

    2016-05-09

    RAND researchers conducted a systematic review that synthesized evidence from randomized controlled trials of St. John's wort (SJW)-used adjunctively or as monotherapy-to provide estimates of its efficacy and safety in treating adults with major depressive disorder. Outcomes of interest included changes in depressive symptomatology, quality of life, and adverse effects. Efficacy meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. In total, 35 studies met inclusion criteria. There is moderate evidence, due to unexplained heterogeneity between studies, that depression improvement based on the number of treatment responders and depression scale scores favors SJW over placebo, and results are comparable to antidepressants. The existing evidence is based on studies testing SJW as monotherapy; there is a lack of evidence for SJW given as adjunct therapy to standard antidepressant therapy. We found no systematic difference between SJW extracts, but head-to-head trials are missing; LI 160 (0.3% hypericin, 1-4% hyperforin) was the extract with the greatest number of studies. Only two trials assessed quality of life. SJW adverse events reported in included trials were comparable to placebo, and were fewer compared with antidepressant medication; however, adverse event assessments were limited, and thus we have limited confidence in this conclusion.

  7. Brain membrane lipids in major depression and anxiety disorders.

    PubMed

    Müller, Christian P; Reichel, Martin; Mühle, Christiane; Rhein, Cosima; Gulbins, Erich; Kornhuber, Johannes

    2015-08-01

    Major depression and anxiety disorders have high prevalence rates and are frequently comorbid. The neurobiological bases for these disorders are not fully understood, and available treatments are not always effective. Current models assume that dysfunctions in neuronal proteins and peptide activities are the primary causes of these disorders. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic throughput in neurons. Lipids may also leave the membrane as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Here we review how membrane lipids, which play roles in the membrane's function as a barrier and a signaling medium for classical transmitter signaling, contribute to depression and anxiety disorders and how this role may provide targets for lipid-based treatment approaches. Preclinical findings have suggested a crucial role for the membrane-forming n-3 polyunsaturated fatty acids, glycerolipids, glycerophospholipids, and sphingolipids in the induction of depression- and anxiety-related behaviors. These polyunsaturated fatty acids also offer new treatment options such as targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes. While clinical trials support this view, effective lipid-based therapies may need more individualized approaches. Altogether, accumulating evidence suggests a crucial role for membrane lipids in the pathogenesis of depression and anxiety disorders; these lipids could be exploited for improved prevention and treatment. This article is part of a Special Issue entitled Brain Lipids.

  8. Smoking and Major Depressive Disorder in Chinese Women

    PubMed Central

    Shi, Shenxun; Gao, Jingfang; Tao, Ming; Zhang, Kerang; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Ying; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S.; Wang, Xumei; Li, Youhui; Flint, Jonathan

    2014-01-01

    Objective To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers. Methods We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status. Results Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence. Conclusions Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors. PMID:25180682

  9. Duloxetine in the treatment of major depressive disorder.

    PubMed

    Goldstein, David J

    2007-04-01

    Since depression impacts all body systems, antidepressant treatments should relieve both the emotional and physical symptoms of depression. Duloxetine demonstrated antidepressant efficacy at a dose of 60 mg qd in two placebo-controlled, randomized, double-blind studies and significantly improved remission rates compared with placebo. Duloxetine-treated patients had significant reduction in severity of the symptoms of depression as assessed by the HAM-D(17), anxious symptoms as measured by the HAM-A and quality of life measures compared to placebo. Duloxetine also improved somatic symptoms, particularly painful symptoms which may have contributed to significantly improved remission rates compared to placebo. Approximately 10% of the 1139 patients with major depressive disorder in placebo-controlled trials discontinued treatment due to an adverse event, compared to 4% of the 777 patients receiving placebo. In addition to nausea (1.4% incidence), which was the most common reason for discontinuation, dizziness, somnolence, and fatigue were the most common AEs reported as reasons for discontinuation and all were considered drug-related. Duloxetine treatment lacks effects on ECG, increases heart rate, and has little effect on blood pressure or weight.

  10. Impact of lifestyle and psychological stress on the development of early onset breast cancer

    PubMed Central

    Li, Ping; Huang, Jialing; Wu, Huina; Fu, Cuixia; Li, Yun; Qiu, Jiajia

    2016-01-01

    Abstract The present study aimed to investigate risk factors for early onset breast cancer that are related to lifestyle and psychological stress. A comparative case–control study was performed among patients from the Department of Breast Surgery in Shanghai Cancer Center of Fudan University. The information regarding risk factors associated with the development of early onset breast cancer was collected using a questionnaire in a face-to-face interview. The distribution of the risk factors associated with the development of early onset breast cancer between the patient group and the control group was analyzed with logistic regression. A total of 582 cases of young patients (≤40 years old) with breast cancer and 540 controls of young patients (≤40 years old) with benign breast disease were included in this study. The risk factors for breast cancer in young women include age at first birth (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88–0.98), history of breast cancer in an immediate family member (OR = 2.36, 95% CI: 1.14–4.89), history of genital surgery (OR = 2.11, 95% CI: 1.16–3.82), active and passive smoking in daily life or the environment (OR = 1.64, 95% CI: 1.19–2.25), weekly intake of soy products (OR = 1.24, 95% CI: 1.02–1.49), use of household cooking oil (OR = 2.04, 95% CI: 1.04–4.00), disharmonious marital status (OR = 1.16, 95% CI: 1.06–1.26), frequent depression (OR = 1.32, 95% CI: 1.00–1.75), and negative emotional experiences (OR = 1.15, 95% CI: 1.03–1.29). Our study could provide the basis for risk assessment and preventive interventions for early onset breast cancer. PMID:27977584

  11. Modelling cognitive affective biases in major depressive disorder using rodents.

    PubMed

    Hales, Claire A; Stuart, Sarah A; Anderson, Michael H; Robinson, Emma S J

    2014-10-01

    Major depressive disorder (MDD) affects more than 10% of the population, although our understanding of the underlying aetiology of the disease and how antidepressant drugs act to remediate symptoms is limited. Major obstacles include the lack of availability of good animal models that replicate aspects of the phenotype and tests to assay depression-like behaviour in non-human species. To date, research in rodents has been dominated by two types of assays designed to test for depression-like behaviour: behavioural despair tests, such as the forced swim test, and measures of anhedonia, such as the sucrose preference test. These tests have shown relatively good predictive validity in terms of antidepressant efficacy, but have limited translational validity. Recent developments in clinical research have revealed that cognitive affective biases (CABs) are a key feature of MDD. Through the development of neuropsychological tests to provide objective measures of CAB in humans, we have the opportunity to use 'reverse translation' to develop and evaluate whether similar methods are suitable for research into MDD using animals. The first example of this approach was reported in 2004 where rodents in a putative negative affective state were shown to exhibit pessimistic choices in a judgement bias task. Subsequent work in both judgement bias tests and a novel affective bias task suggest that these types of assay may provide translational methods for studying MDD using animals. This review considers recent work in this area and the pharmacological and translational validity of these new animal models of CABs.

  12. Circuits regulating pleasure and happiness in major depression.

    PubMed

    Loonen, A J M; Ivanova, S A

    2016-02-01

    The introduction of selective serotonin reuptake inhibitors has gradually changed the borders of the major depression disease class. Anhedonia was considered a cardinal symptom of endogenous depression, but the potential of selective serotonin reuptake inhibitors to treat anxiety disorders has increased the relevance of stress-induced morbidity. This shift has led to an important heterogeneity of current major depressive disorder. The complexity can be disentangled by postulating the existence of two different but mutually interacting neuronal circuits regulating the intensity of anhedonia (lack of pleasure) and dysphoria (lack of happiness). These circuits are functionally dominated by partly closed limbic (regulating misery-fleeing behaviour) and extrapyramidal (regulating reward-seeking behaviour) cortico-striato-thalamo-cortical (CSTC) circuits. The re-entry circuits include the shell and core parts of the accumbens nucleus, respectively. Pleasure can be considered to result from finding relief from the hypermotivation to exhibit rewarding behaviour, and happiness from finding relief from negative or conflicting circumstances. Hyperactivity of the extrapyramidal CSTC circuit results in craving, whereas hyperactivity of the limbic system results in dysphoria.

  13. Inpatients with major depressive disorder: Psychometric properties of the new Multidimensional Depression Scale.

    PubMed

    Darharaj, Mohammad; Habibi, Mojtaba; Power, Michael J; Farzadian, Farzaneh; Rahimi, Maesoumeh; Kholghi, Habibeh; Kazemitabar, Maryam

    2016-12-01

    The New Multi-dimensional Depression Scale (NMDS) is one of the most comprehensive scales that measures depression symptoms in four domains, including emotional, cognitive, somatic, and interpersonal. This study aimed to evaluate the factor structure and psychometric properties of the NMDS in a group of Iranian inpatients with Major Depressive Disorder (MDD). At first, the scale was translated into Persian and used as part of a battery consisting of the Beck Depression Inventory-II (BDI-II), Oxford Happiness Inventory (OHI), Beck Anxiety Inventory (BAI), and Short Form Health Survey (SF-36). The battery was administered to 271 inpatients with MDD (90 men and 181 women) aged from 18 to 60 who had been referred to psychiatric hospitals in Tehran, Iran. Confirmatory factor analysis of the Persian version of the NMDS upheld its original four-factor structure. Moreover, the results showed its good internal consistency (Cronbach's alpha coefficient ranging from 0.70 for the emotional subscale to 0.83 for the interpersonal subscale). In addition, the NMDS scores were correlated with other constructs in empirically and theoretically expected ways, which provides evidence for the convergent (positive significant relationships with anxiety and cognitive and somatic-affective symptoms of depression) and divergent (negative significant relationships with happiness and mental health and physical health) validity of the scale. These findings supported the Persian version of the NMDS as a reliable and valid measure for the assessment of depression symptoms in patients with MDD.

  14. Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression.

    PubMed

    Karabatsiakis, A; Böck, C; Salinas-Manrique, J; Kolassa, S; Calzia, E; Dietrich, D E; Kolassa, I-T

    2014-06-10

    Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

  15. Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

    PubMed

    Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

    2012-04-30

    Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

  16. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

    PubMed Central

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos e

    2015-01-01

    Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear. PMID:26097750

  17. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts.

    PubMed

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; de Matos E Souza, Fábio Gomes

    2015-01-01

    Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words "bipolar disorder," "suicide attempts," "cannabis," "marijuana," "early age at onset," and "early onset." Results. The following percentages in bipolar patients were found: suicide attempts 3.6-42%; suicide attempts and substance use 5-60%; suicide attempts and cannabis use 15-42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

  18. Evaluation of periodontitis in hospital outpatients with major depressive disorder

    PubMed Central

    Solis, A. C. O.; Marques, A. H.; Pannuti, C. M.; Lotufo, R. F. M.; Lotufo-Neto, F.

    2013-01-01

    Background and Objective Major depressive disorder (MDD) has been associated with alterations in the neuroendocrine system and immune function and may be associated with an increased susceptibility to cardiovascular disease, cancer and autoimmune/inflammatory disease. This study was conducted to investigate the relationship between periodontitis and MDD in a convenience sample of hospital outpatients. Material and Methods The sample consisted of 72 physically healthy subjects (36 outpatients with MDD and 36 age-matched controls [± 3 years]). Patients with bipolar disorder, eating disorders and psychotic disorders were excluded. Probing pocket depth and clinical attachment level were recorded at six sites per tooth. Depression was assessed by means of Structured Clinical Interview for DSM-IV. Results Extent of clinical attachment level and probing pocket depth were not different between controls and subjects with depression for the following thresholds: ≥ 3 mm (Mann-Whitney, p = 0.927 and 0.756); ≥ 4 mm (Mann-Whitney, p = 0.656 and 0.373); ≥ 5 mm (Mann-Whitney, p = 0.518 and 0.870);, and ≥ 6 mm (Mann-Whitney, p = 0.994 and 0.879). Depression parameters were not associated with clinical attachment level ≥ 5 mm in this sample. Smoking was associated with loss of attachment ≥ 5 mm in the multi-variable logistic regression model (odds ratio = 6.99, 95% confidence interval = 2.00–24.43). Conclusions In this sample, periodontal clinical parameters were not different between patients with MDD and control subjects. There was no association between depression and periodontitis. PMID:23586804

  19. Clinical features of soft bipolarity in major depressive inpatients.

    PubMed

    Utsumi, Takeshi; Sasaki, Tsukasa; Shimada, Iwao; Mabuchi, Mayuko; Motonaga, Takuro; Ohtani, Toshiyuki; Tochigi, Mamoru; Kato, Nobumasa; Nanko, Shinichiro

    2006-10-01

    Because of the difficulties of ascertaining episode of hypomania by past history of the patients, it is of clinical value to find variables which predict the development of bipolar II disorder in depressive patients. Taking advantage of relatively long hospitalization, the authors tried to elucidate fine clinical features of the soft bipolarity. The subjects were 39 patients with Major Depressive Episode, diagnosed according to the 4th edition of the Diagnostic and Statistical Manual criteria. Among them, 15 patients were diagnosed as bipolar II disorder (BPII), whereas 24 patients were with unipolar depression (UP), using a structured clinical interview to assess the mood spectrum (SCI-MOODS). In addition to ordinary clinical and demographic variables, the authors studied fine symptomatology of depression, premorbid personality, and interpersonal relationship. Continuous variables were analyzed by t-test. Categorical variables were tested by chi2 analysis. In terms of premorbid personality, manic type (Zerssen) was found more frequently in BPII (UP 2/24, BPII 9/15, P < 0.05). Patients with BPII tended to show apparently quick disappearance of depressive symptoms (UP 2/24, BPII 9/15, P = 0.01). The most prominent result was a high prevalence of comorbidity of borderline personality disorder (BPD) among BPII (UP 0/24, BPII 6/15, P = 0.02). As Akiskal indicated that mood lability represents the most powerful predictor of hypomanias, patients with BPII showed quick response in mood to admission. The current subjects with BPII had high frequency of manic type of premorbid personality, indicating the usefulness of this variable for the prediction of hypomanias. Finally, the authors could observe development of BPD during hospitalization exclusively among BPII, to support the possibility of BPD as a state effect of BPII.

  20. Adjunctive Brexpiprazole: A Review in Major Depressive Disorder.

    PubMed

    McKeage, Kate

    2016-02-01

    Brexpiprazole (Rexulti(®)) is a serotonin-dopamine activity modulator, with a unique receptor binding profile and low intrinsic D2 activity suggestive of a lower potential than aripiprazole to cause activation-like adverse effects, such as akathisia. The drug was recently approved by the US FDA for adjunctive therapy with antidepressant treatment (ADT) in patients with major depressive disorder (MDD). In two phase III trials, adjunctive oral brexpiprazole 2 or 3 mg once daily was more effective than monotherapy with ADT in improving depressive symptoms in adults with MDD who demonstrated an incomplete response to previous treatment with ADT. Adjunctive brexpiprazole was generally well tolerated in clinical trials, which included treatment periods of up to 52 weeks. Results of ongoing trials should help position the drug in the treatment of MDD. In the meantime, brexpiprazole provides a valid option for patients with persistent symptoms despite standard antidepressant therapy.

  1. From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression

    PubMed Central

    Slavich, George M.; Irwin, Michael R.

    2014-01-01

    Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation. PMID:24417575

  2. The association between depressive symptoms, cognitive function, and inflammation in major depression.

    PubMed

    Krogh, Jesper; Benros, Michael E; Jørgensen, Martin Balslev; Vesterager, Lone; Elfving, Betina; Nordentoft, Merete

    2014-01-01

    The purpose of this study was to assess the association between IL-6 and CRP with depressive items and cognitive function. We included 112 outpatients with major depression from an exercise trial and 57 healthy controls. IL-6, high sensitive CRP (hsCRP), and cognitive function were assessed in all subjects. After baseline assessment, patients were randomised to either a 3months exercise intervention or an exercise control group. Post-intervention IL-6, hsCRP, depressive symptoms, and cognitive function were reassessed in the patient group. IL-6 and hsCRP were significantly increased in depressed patients compared to healthy controls (p=0.02 and 0.04). These differences were no longer significant after adjustment for lifestyle associated variables. We found no association between immune markers and specific depressive symptoms at baseline or as change over time. Regarding the cognitive tests, IL-6 was positively associated with Serial sevens (p=0.008) and hsCRP was inversely associated with Trail making A (p=0.02) and design fluency (p=0.001) at baseline. At 3months follow-up IL-6 and hsCRP levels did not significantly change from baseline and did not differ between the two patient groups. Depression scores was lower compared to baseline but did not differ between groups. Combining the two groups, a decrease in IL-6 was associated to decreased verbal fluency (p=0.02), and a decrease in hsCRP was associated with improvement in Trail making A (p=0.005). In conclusion, the level of IL-6 and hsCRP was increased in depressed outpatients but was not associated to specific depressive symptoms. In terms of cognitive function, we found that higher hsCRP levels were associated to lower psychomotor speed both at baseline and at follow-up.

  3. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression.

    PubMed

    Slavich, George M; Irwin, Michael R

    2014-05-01

    Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.

  4. Susceptibility genetic variants associated with early-onset colorectal cancer.

    PubMed

    Giráldez, María Dolores; López-Dóriga, Adriana; Bujanda, Luis; Abulí, Anna; Bessa, Xavier; Fernández-Rozadilla, Ceres; Muñoz, Jenifer; Cuatrecasas, Miriam; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Piqué, Josep M; Carracedo, Angel; Ruiz-Ponte, Clara; Cosme, Angel; Enríquez-Navascués, José María; Moreno, Victor; Andreu, Montserrat; Castells, Antoni; Balaguer, Francesc; Castellví-Bel, Sergi

    2012-03-01

    Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies.

  5. Latin America: native populations affected by early onset periodontal disease.

    PubMed

    Nowzari, Hessam; Botero, Javier Enrique

    2011-06-01

    Millions of individuals are affected by early onset periodontal disease in Latin America, a continent that includes more than 20 countries. The decision-makers claim that the disease is not commonly encountered. In 2009, 280,919 authorized immigrants were registered in the United States versus 5,460,000 unauthorized (2,600,000 in California). The objective of the present article is to raise awareness about the high prevalence of the disease among Latin Americans and the good prognosis of preventive measures associated with minimal financial cost.

  6. Parental psychopathology and reports of the childhood home environment in adults with early-onset dysthymic disorder.

    PubMed

    Lizardi, H; Klein, D N

    2000-02-01

    In previous studies, patients with dysthymic disorder (DD) have reported significantly more adverse early home environments than patients with episodic major depressive disorder (MDD) and normal controls. However, DD is also associated with increased rates of mood and personality disorders in first-degree relatives, raising the possibility that the DD-early adversity relationship may be due to the confounding effects of parental psychopathology. The present study addressed this issue using a sample of 97 adult outpatients with early-onset DD, 45 adult outpatients with episodic MDD, and 45 normal controls, and their first-degree relatives. The early home environment was assessed with semi-structured interviews and self-report inventories. Parental psychopathology was assessed using semi-structured direct and family history interviews, and diagnoses were assigned using the best-estimate procedure. Results indicated that parental mood and personality disorders were strongly associated with probands' reports of early adversity. However, patients with DD continued to differ significantly from patients with episodic MDD and normal controls after controlling for parental psychopathology.

  7. Structural abnormality of the corticospinal tract in major depressive disorder

    PubMed Central

    2014-01-01

    Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

  8. Premature adrenarche: novel lessons from early onset androgen excess.

    PubMed

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  9. Longitudinal Brain Changes in Early-Onset Psychosis

    PubMed Central

    Arango, Celso; Moreno, Carmen; Martínez, Salvador; Parellada, Mara; Desco, Manuel; Moreno, Dolores; Fraguas, David; Gogtay, Nitin; James, Anthony; Rapoport, Judith

    2008-01-01

    Progressive losses of cortical gray matter volumes and increases in ventricular volumes have been reported in patients with childhood-onset schizophrenia (COS) during adolescence. Longitudinal studies suggest that the rate of cortical loss seen in COS during adolescence plateaus during early adulthood. Patients with first-episode adolescent-onset schizophrenia show less marked progressive changes, although the number of studies in this population is small. Some studies show that, although less exaggerated, progressive changes are also present in nonschizophrenia early-onset psychosis. The greater loss of brain tissue seen in COS, even some years after the first episode, as compared to adolescent- or adult-onset schizophrenia may be due to variables such as sample bias (more severe, treatment refractory sample of childhood-onset patients studied), a process uniquely related to adolescent development in COS, differential brain effects of drug treatment in this population, clinical outcome, or interactions among these variables. Findings from both cross-sectional studies of first-episode patients and longitudinal studies in COS and adolescent onset support the concept of early-onset schizophrenia as a progressive neurodevelopmental disorder with both early and late developmental abnormalities. Future studies should look for correlates at a cellular level and for pathophysiological explanations of volume changes in these populations. The association of risk genes involved in circuitries associated with schizophrenia and their relationship to developmental trajectories is another promising area of future research. PMID:18234701

  10. Evaluating the Near-Term Infant for Early Onset Sepsis

    PubMed Central

    Jordan, Jeanne A.; Durso, Mary Beth; Butchko, Allyson R.; Jones, Judith G.; Brozanski, Beverly S.

    2006-01-01

    Although the rate of early onset sepsis in the near-term neonate is low (one to eight of 1000 cases), the rate of mortality and morbidity is high. As a result, infants receive multiple, broad-spectrum antibiotic therapy, many for up to 7 days despite blood cultures showing no growth. Maternal intrapartum antibiotic prophylaxis and small blood volume collections from infants are cited as reasons for the lack of confidence in negative culture results. Incorporating an additional, more rapid test could facilitate a more timely diagnosis in these infants. To this end, a 16S rDNA polymerase chain reaction (PCR) assay was compared to blood culturing for use as a tool in evaluating early onset sepsis. Of 1751 neonatal intensive care unit admissions that were screened, 1233 near-term infants met inclusion criteria. Compared to culture, PCR demonstrated excellent analytical specificity (1186 of 1216, 97.5%) and negative predictive value (1186 of 1196, 99.2%); however, PCR failed to detect a significant number of culture-proven cases. These findings underscore the cautionary stance that should be taken at this time when considering the use of a molecular amplification test for diagnosing neonatal sepsis. The experience gained from this study illustrates the need for changes in sample collection and preparation techniques so as to improve analytical sensitivity of the assay. PMID:16825509

  11. Association of reticular pseudodrusen and early onset drusen.

    PubMed

    De Bats, Flore; Wolff, Benjamin; Mauget-Faÿsse, Martine; Meunier, Isabelle; Denis, Philippe; Kodjikian, Laurent

    2013-01-01

    Purpose. To report an association between reticular pseudodrusen, located above the retinal pigment epithelium (RPE), and Early Onset Drusen (EOD) as described using Spectral-Domain Optical Coherence Tomography (SD-OCT). Methods. Eight patients (16 eyes) with EOD were examined. EOD were classified into three entities called Large Colloid Drusen (LCD), Malattia Leventinese (ML), and Cuticular Drusen (CD). Best-corrected visual acuity, fundus examination, color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and SD-OCT were performed in all study patients. Results. Four patients had LCD, 2 had ML, and 2 had CD. Reticular pseudodrusen were observed with SD-OCT in all study patients; all these patients had hyperreflective lesions above and below the RPE. Conclusion. Early Onset Drusen appear to be associated with reticular pseudodrusen. SD-OCT is helpful in distinguishing the location of the deposits that are above and below the RPE in EOD. Further studies are needed to understand the role of reticular pseudodrusen in the pathophysiology of EOD.

  12. Association of Reticular Pseudodrusen and Early Onset Drusen

    PubMed Central

    De Bats, Flore; Wolff, Benjamin; Mauget-Faÿsse, Martine; Meunier, Isabelle; Denis, Philippe; Kodjikian, Laurent

    2013-01-01

    Purpose. To report an association between reticular pseudodrusen, located above the retinal pigment epithelium (RPE), and Early Onset Drusen (EOD) as described using Spectral-Domain Optical Coherence Tomography (SD-OCT). Methods. Eight patients (16 eyes) with EOD were examined. EOD were classified into three entities called Large Colloid Drusen (LCD), Malattia Leventinese (ML), and Cuticular Drusen (CD). Best-corrected visual acuity, fundus examination, color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and SD-OCT were performed in all study patients. Results. Four patients had LCD, 2 had ML, and 2 had CD. Reticular pseudodrusen were observed with SD-OCT in all study patients; all these patients had hyperreflective lesions above and below the RPE. Conclusion. Early Onset Drusen appear to be associated with reticular pseudodrusen. SD-OCT is helpful in distinguishing the location of the deposits that are above and below the RPE in EOD. Further studies are needed to understand the role of reticular pseudodrusen in the pathophysiology of EOD. PMID:24563787

  13. Animal models of major depression and their clinical implications.

    PubMed

    Czéh, Boldizsár; Fuchs, Eberhard; Wiborg, Ove; Simon, Mária

    2016-01-04

    Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field.

  14. [Elephantiasis nostras verrucosa in a patient with major depressive disorder].

    PubMed

    Simón Llanes, J; Coll Vilar, I; Tamarit Francés, C; Niubó de Castro, I

    2012-01-01

    Elephantiasis nostras verrucosa is a rare condition characterised by papules, verrucous lesions, fibrosis and deformity of the affected area. It is caused by chronic lymphedema that could be congenital or produced by a non-associated infection (such as tuberculosis, mycotic infection, syphilis), surgery, radiotherapy, trauma, neoplastic obstruction, obesity, portal hypertension, or congestive heart failure. There is no standard treatment for this rare skin disorder. Depending on the cause and the severity, the treatment can be medical or surgical. We report the case of a man seen in our hospital with a major depression and elephantiasis nostras verrucosa skin lesions on both legs, who was successfully treated with surgical debridement and conservative measures.

  15. The varied clinical presentations of major depressive disorder.

    PubMed

    Rush, A John

    2007-01-01

    DSM-IV major depressive disorder (MDD) is a clinical syndrome notable for heterogeneity of its clinical presentation, genetics, neurobiology, clinical course, and treatment responsiveness. In an attempt to make sense of this heterogeneity, clinicians and researchers have proposed a number of MDD "subtypes" based on differences in characteristic symptoms (e.g., atypical, melancholic, psychotic), onset (e.g., early vs. late, post-partum, seasonal), course of illness (e.g., single vs. recurrent, chronic, double), and severity. This article provides a brief review of the status of several of the most common subtypes in terms of their clinical features, biological correlates, course of illness, and treatment implications.

  16. Major Depressive Disorder in the older adult: implications for women.

    PubMed

    Goldstein, Reed D; Gruenberg, Alan M

    2007-01-01

    Mood disorders manifest across the life span yet often go undiagnosed and untreated. Increasingly, Major Depressive Disorder (MDD) in the older adult is recognized as a frequently occurring, heterogeneous psychiatric illness that impacts the individual and family, one's physical health, and society. Women are more likely to be diagnosed with MDD than men and therefore it is important to identify specific risk factors and other distinguishing features. This article reviews the descriptive characteristics, epidemiology, etiology and pathophysiology, course and natural history, and assessment and treatment of MDD with specific focus on women and aging.

  17. Dynamic Resting-State Functional Connectivity in Major Depression.

    PubMed

    Kaiser, Roselinde H; Whitfield-Gabrieli, Susan; Dillon, Daniel G; Goer, Franziska; Beltzer, Miranda; Minkel, Jared; Smoski, Moria; Dichter, Gabriel; Pizzagalli, Diego A

    2016-06-01

    Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.

  18. Long-term treatment of major depressive disorder with paroxetine.

    PubMed

    Duboff, E A

    1993-12-01

    Recurrent unipolar depression is a common, but undertreated disorder. Many patients require long-term maintenance therapy, and full doses of antidepressant agents may be preferred for the prevention of relapse. We report results of a 1-year, multicenter, open-label study of paroxetine (10 to 50 mg/day) in 433 patients with major depressive disorder, with additional data from 110 patients who entered a long-term extension of the study. The primary measures of efficacy were the Hamilton Rating Scale for Depression (HAM-D) total and Clinical Global Impression (CGI) severity of illness scores. During the first 6 weeks of therapy, the mean HAM-D total declined approximately 50% (from 27.9 to 13.5), with continued improvement, at an attenuated rate, throughout the first year. At the end of 1 year, the mean HAM-D total was 6.9. Similarly, the CGI severity of illness score declined from 4.6 at baseline to 2.8 at week 6 and to 1.7 at the end of 1 year. Remission was maintained in the population that entered the long-term extension, with mean HAM-D total and CGI severity of illness scores of 6.4 and 1.8, respectively, after 2.5 years, and 4.2 and 1.3 after 4 years. The most common adverse events reported during long-term treatment with paroxetine were somnolence, nausea, headache, and sweating. Pharmacokinetic analysis showed no clear correlation between the concentrations of paroxetine in plasma and either clinical efficacy or tolerability. There was no increased drug accumulation during long-term treatment. Side effects tended to occur early during therapy; and no new side effects emerged during the long-term extension. These results suggest that paroxetine is effective and well tolerated in the long-term treatment of depression.

  19. [Therapeutic application of repetitive transcranial magnetic stimulation for major depression].

    PubMed

    Nakamura, Motoaki

    2012-01-01

    It has been reported that approximately one third of patients with major depression are medication-resistant. In spite of partial responsiveness to antidepressants, most of the medication-resistant patients remain incompletely remitted without successful social reintegration. Symptom severity could be mild to moderate for many of them due to the incomplete remission, and, thus, electroconvulsive therapy is not applicable for them. However, they usually feel some difficulty performing cognitive behavioral therapy or social rehabilitation training due to residual symptoms such as thought inhibition and hypobulia. Under such conditions, those patients are longing for treatment options complementary to antidepressants, for less painful social reintegration. In October 2008, the Food and Drug Administration (FDA) of the United States finally approved repetitive Transcranial Magnetic Stimulation (rTMS) for medication-resistant patients with major depression. The main reason for the FDA approval was that rTMS had shown similar effectiveness (effect size around 0.39 in a recent meta-analysis) to antidepressants for medication-resistant patients without serious adverse effects. TMS is a brain stimulation methodology employing magnetic energy which can penetrate the skull bone without energy decay, and, thus, eddy currents induced by TMS can stimulate cerebral cortices effectively and locally. When TMS is repetitively delivered over several hundreds of pulses within a session, stimulation effects can be observed beyond the stimulation period as aftereffects. Moreover, when a daily rTMS session is repeated over several weeks, rTMS could have antidepressant effects. Clinical trials of rTMS for depression have employed two kinds of rTMS protocol of high-frequency (facilitatory) rTMS over the left Dorsolateral Prefrontal Cortex (DLPFC) and low-frequency (inhibitory) rTMS over the right DLPFC. Although the antidepressant action of rTMS over DLPFC has not been fully elucidated

  20. Modelling cognitive affective biases in major depressive disorder using rodents

    PubMed Central

    Hales, Claire A; Stuart, Sarah A; Anderson, Michael H; Robinson, Emma S J

    2014-01-01

    Major depressive disorder (MDD) affects more than 10% of the population, although our understanding of the underlying aetiology of the disease and how antidepressant drugs act to remediate symptoms is limited. Major obstacles include the lack of availability of good animal models that replicate aspects of the phenotype and tests to assay depression-like behaviour in non-human species. To date, research in rodents has been dominated by two types of assays designed to test for depression-like behaviour: behavioural despair tests, such as the forced swim test, and measures of anhedonia, such as the sucrose preference test. These tests have shown relatively good predictive validity in terms of antidepressant efficacy, but have limited translational validity. Recent developments in clinical research have revealed that cognitive affective biases (CABs) are a key feature of MDD. Through the development of neuropsychological tests to provide objective measures of CAB in humans, we have the opportunity to use ‘reverse translation’ to develop and evaluate whether similar methods are suitable for research into MDD using animals. The first example of this approach was reported in 2004 where rodents in a putative negative affective state were shown to exhibit pessimistic choices in a judgement bias task. Subsequent work in both judgement bias tests and a novel affective bias task suggest that these types of assay may provide translational methods for studying MDD using animals. This review considers recent work in this area and the pharmacological and translational validity of these new animal models of CABs. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24467454

  1. Psychosocial Functioning in Youths at High Risk to Develop Major Depressive Disorder.

    ERIC Educational Resources Information Center

    Birmaher, Boris; Bridge, Jeffrey A.; Williamson, Douglas E.; Brent, David A.; Dahl, Ronald E.; Axelson, David A.; Dorn, Lorah D.; Ryan, Neal D.

    2004-01-01

    Objective: To compare the psychosocial functioning of children and adolescents at high risk of major depressive disorder with youths with acute major depressive disorder and healthy controls. Method: High-risk (n = 57), major depressive disorder (n = 71), and healthy control (n = 48) youths and their families were recruited from 1987 to 1996 and…

  2. Mental Health Literacy of Those with Major Depression and Suicidal Ideation: An Impediment To Help Seeking.

    ERIC Educational Resources Information Center

    Goldney, Robert D.; Fisher, Laura J.; Wilson, David H.; Cheok, Frida

    2002-01-01

    A vignette depicting classical features of major depression was presented to subjects along with questions related to mental health literacy. Responses of those with major depression were compared to those of a control group. Results demonstrated that despite increased professional contact by those with major depression and suicidal ideation,…

  3. Kappa Opioids, Salvinorin A and Major Depressive Disorder

    PubMed Central

    Taylor, George T.; Manzella, Francesca

    2016-01-01

    Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research. PMID:26903446

  4. Kappa Opioids, Salvinorin A and Major Depressive Disorder.

    PubMed

    Taylor, George T; Manzella, Francesca

    2016-01-01

    Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.

  5. Anhedonia and major depression: the role of agomelatine.

    PubMed

    Di Giannantonio, Massimo; Martinotti, Giovanni

    2012-01-01

    Anhedonia is a condition in which the capacity to experience pleasure is totally or partially lost. Although anhedonia is a feature of major depressive disorder according to DSM IV criteria for major depression diagnosis, so far it has received relatively little attention. The scale that is most commonly used in the measurement of anhedonia is the Snaith-Hamilton Pleasure Scale (SHAPS), a brief 14-item self-report questionnaire designed to measure hedonic tone and its absence. Two studies have described the efficacy of agomelatine in the treatment of anhedonia: an open-label study and a comparative trial versus the antidepressant venlafaxine XR. In both studies agomelatine significantly reduced anhedonia, as indicated using the SHAPS. This reduction was observed after the first week of treatment (P<0.05) and at different times until the end of the trial. Moreover, in the comparative trial, a significant difference between groups was observed in favor of agomelatine, after 1 (P<0.05), 2 (P<0.01), and 8 weeks (P<0.01). The possible effect of agomelatine on anhedonia may represent a novel area of interest among antidepressant agents and deserves further investigation, with larger samples and double-blind placebo-controlled designs.

  6. Italian neurologists' perception on cognitive symptoms in major depressive disorder.

    PubMed

    Neri, G; Serrati, C; Zolo, P; Cataldo, N; Ripellino, C

    2016-09-01

    The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians' perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists' perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists' socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients' functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists' perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.

  7. A Study of the Predictive Validity of the Children's Depression Inventory for Major Depression Disorder in Puerto Rican Adolescents

    ERIC Educational Resources Information Center

    Rivera-Medina, Carmen L.; Bernal, Guillermo; Rossello, Jeannette; Cumba-Aviles, Eduardo

    2010-01-01

    This study aims to evaluate the predictive validity of the Children's Depression Inventory items for major depression disorder (MDD) in an outpatient clinic sample of Puerto Rican adolescents. The sample consisted of 130 adolescents, 13 to 18 years old. The five most frequent symptoms of the Children's Depression Inventory that best predict the…

  8. Cerebellar Pathology in Early Onset and Late Onset Essential Tremor.

    PubMed

    Kuo, Sheng-Han; Wang, Jie; Tate, William J; Pan, Ming-Kai; Kelly, Geoffrey C; Gutierrez, Jesus; Cortes, Etty P; Vonsattel, Jean-Paul G; Louis, Elan D; Faust, Phyllis L

    2017-04-01

    Early onset and late onset essential tremor (ET) cases differ in several respects. Whether they differ with respect to cerebellar pathologic changes remains to be determined. We quantified a broad range of postmortem features (Purkinje cell (PC) counts, PC axonal torpedoes and associated axonal changes, heterotopic PCs, and hairy basket ratings) in 30 ET cases with age of tremor onset <50 years, 30 ET cases with age of tremor onset ≥50 years, and 30 controls (total n = 90). We also used two alternative age of onset cut-points (<40 vs. ≥40 years, and <60 vs. ≥60 years) to define early onset vs. late onset ET. We found that ET cases with tremor onset <50 years and tremor onset ≥50 years had similar PC counts (8.78 ± 1.70 vs. 8.86 ± 1.24, p = 0.839), PC axonal torpedo counts (17.87 ± 18.27 [median =13.00] vs. 12.90 ± 10.60 [median =9.0], p = 0.486) and associated axonal pathology (all p values >0.05), heterotopic PC counts (9.90 ± 11.55 [median =6.00] vs. 5.40 ± 5.10 [median =3.50], p = 0.092), and hairy basket ratings (1.95 ± 0.62 [median =2.00] vs. 2.05 ± 0.92 [median =2.00], p = 0.314). When using the age of onset cut-points of 40 or 60 years, results were similar. Early onset and late onset ET cases share similar cerebellar postmortem features. These data do not support the notion that these age-of-onset related forms of ET represent distinct clinical-pathological entities.

  9. Is the NACP/Synuclein gene involved in early-onset Alheimer`s disease?

    SciTech Connect

    Champion, D.; Clerget-Darpoux, F.; Frebourg, T.

    1994-09-01

    The major component of senile plaques (SP), the most specific histologic lesion of Alzheimer`s disease (AD) is the A4 peptide, derived from a large precursor protein (APP). Recently, a second major component of SP has been isolated. This 35 AA peptide was named non-A4 component amyloid (NAC) and its precursor - a 140 AA protein - was named NACP. Computer homology search has allowed us to establish that the NACP gene is homologous to the rat synuclein gene which is expressed in neurons. Since APP mutations have been shown to cause early-onset Alzheimer`s disease (EOAD) in several families, we investigated whether the NACP/synuclein gene was also involved in familial early-onset Alzheimer`s disease (FEOAD). RT-PCR and direct sequencing of the entire NACP open reading frame did not reveal any alteration of the NACP coding sequence in lymphocytes of 26 unrelated FEOAD patients. We showed that the NACP/synuclein gene was alternatively spliced and that the different transcripts potentially encoded for distinct proteins all containing the NAC peptide. Accumulation of NAC in SP might result from a dysregulation of NACP/synuclein expression.

  10. Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder

    PubMed Central

    McGrath, Callie L.; Kelley, Mary E.; Holtzheimer, Paul E.; Dunlop, Boadie W.; Craighead, W. Edward; Franco, Alexandre R.; Craddock, R. Cameron; Mayberg, Helen S.

    2015-01-01

    IMPORTANCE Currently, fewer than 40% of patients treated for major depressive disorder achieve remission with initial treatment. Identification of a biological marker that might improve these odds could have significant health and economic impact. OBJECTIVE To identify a candidate neuroimaging “treatment-specific biomarker” that predicts differential outcome to either medication or psychotherapy. DESIGN Brain glucose metabolism was measured with positron emission tomography prior to treatment randomization to either escitalopram oxalate or cognitive behavior therapy for 12 weeks. Patients who did not remit on completion of their phase 1 treatment were offered enrollment in phase 2 comprising an additional 12 weeks of treatment with combination escitalopram and cognitive behavior therapy. SETTING Mood and anxiety disorders research program at an academic medical center. PARTICIPANTS Men and women aged 18 to 60 years with currently untreated major depressive disorder. INTERVENTION Randomized assignment to 12 weeks of treatment with either escitalopram oxalate (10–20 mg/d) or 16 sessions of manual-based cognitive behavior therapy. MAIN OUTCOME AND MEASURE Remission, defined as a 17-item Hamilton Depression Rating Scale score of 7 or less at both weeks 10 and 12, as assessed by raters blinded to treatment. RESULTS Positive and negative predictors of remission were identified with a 2-way analysis of variance treatment (escitalopram or cognitive behavior therapy) × outcome (remission or nonresponse) interaction. Of 65 protocol completers, 38 patients with clear outcomes and usable positron emission tomography scans were included in the primary analysis: 12 remitters to cognitive behavior therapy, 11 remitters to escitalopram, 9 nonresponders to cognitive behavior therapy, and 6 nonresponders to escitalopram. Six limbic and cortical regions were identified, with the right anterior insula showing the most robust discriminant properties across groups (effect size

  11. Atypical antipsychotics in the treatment of early-onset schizophrenia

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

  12. Childhood Risk Factors for Early-Onset Drinking*

    PubMed Central

    Donovan, John E.; Molina, Brooke S. G.

    2011-01-01

    Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

  13. Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

    PubMed

    Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

    2016-02-28

    The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD.

  14. Dysregulated relationship of inflammation and oxidative stress in major depression

    PubMed Central

    Rawdin, B.J.; Mellon, S.H.; Dhabhar, F.S.; Epel, E.S.; Puterman, E.; Su, Y.; Burke, H.M.; Reus, V.I.; Rosser, R.; Hamilton, S.P.; Nelson, J.C.; Wolkowitz, O.M.

    2012-01-01

    Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n = 20) before and after 8 weeks of open-label sertraline treatment (n = 17), compared to healthy non-depressed controls (n = 20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p < 0.05) and were negatively correlated with IL-10 concentrations (p < 0.01). Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/IL-10 (p < 0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio. After MDD subjects were treated with sertraline for 8 weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/IL-10 ratio. These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD. Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment. These findings may help explain the increased risk of comorbid medical illnesses in MDD. PMID:23201587

  15. Altered brain network modules induce helplessness in major depressive disorder

    PubMed Central

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

    2017-01-01

    Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

  16. Do reasons for major depression act as causes?

    PubMed Central

    Kendler, KS; Myers, J; Halberstadt, LJ

    2011-01-01

    We make sense of human behavior using reasons, which produce understanding via a subjective empathy-based first-person perspective and causes, which leads to explanations utilizing objective facts about the world assessed scientifically. We evaluate the common sense hypothesis that for episodes of major depression (MD), reasons act as causes. That is, individuals who have highly understandable depressive episodes will have, on average, fewer objective scientifically validated causes than those who have un-understandable episodes. The understandability of a MD as defined by the Diagnostic and Statistical Manual, 4th Edition (DSM IV) experienced in the past year in 630 personally interviewed twins from a population-based registry was rated, with high reliability, from rich contextual information. We predicted, from these understandability ratings, via linear and logistic regression, 12 validated risk factors for MD reflecting genetic and long-term environmental liability. No significant association was observed between 11 of these indices and the understandability of the depressive episode. The only significant finding—higher cotwin risk for MD associated with greater understandability— was opposite that predicted by the reasons-as-causes hypothesis. Our results do not support the hypothesis that reasons for MD act as causes. These findings, unlikely to result from low power, may be explicable from an empirical and/or philosophical perspective. Our results are, however, consistent with ‘the trap of meaning’ hypothesis, which suggests that understanding does not equal explanation and that while reasons may be critical to help us empathize with our patients, they are unreliable indices of objective risk factors for illness. PMID:21383746

  17. Transdermal selegiline for the treatment of major depressive disorder

    PubMed Central

    Lee, Kelly C; Chen, Jack J

    2007-01-01

    Non-selective inhibition of monoamine oxidase (MAO) enzymes (ie, isoforms A and B) in the brain are associated with clinically significant antidepressant effects. In the US, the selegiline transdermal system (STS; EMSAM) is the first antidepressant transdermal delivery system to receive Food and Drug Administration (FDA) approved labeling for the treatment of major depressive disorder (MDD). Currently, the use of orally administered MAO inhibitor antidepressants (eg, phenelzine, tranylcypromine) is limited by the risk of tyramine-provoked events (eg, acute hypertension and headache, also known as the “cheese reaction”) when combined with dietary tyramine. The selegiline transdermal system is the only MAOI available in the US for the treatment of MDD that does not require dietary restriction at the clinically effective dose of 6 mg/24 hours. Delivery of selegiline transdermally (EMSAM®) bypasses hepatic first pass metabolism, thereby avoiding significant inhibition of gastrointestinal and hepatic MAO-A activity (ie, reduced risk of tyramine-provoked events) while still providing sufficient levels of selegiline in the brain to produce an antidepressant effect. At dosages of 6–12 mg/24 hours, EMSAM has been shown to improve symptoms of depression, have good tolerability, and have high rates of medication adherence. However, at higher doses of EMSAM (ie, 9 mg/24 hours or more), dietary restriction of tyramine intake is recommended. The introduction of EMSAM overcomes many of the safety concerns affiliated with the conventional oral MAO inhibitors and EMSAM may be considered another strategy for the treatment of MDD, especially in patients who cannot tolerate oral antidepressants, are poorly adherent, who present with atypical depressive symptoms, or have failed other antidepressants. PMID:19300583

  18. The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder.

    PubMed

    Abdallah, Chadi G; Jackowski, Andrea; Salas, Ramiro; Gupta, Swapnil; Sato, João R; Mao, Xiangling; Coplan, Jeremy D; Shungu, Dikoma C; Mathew, Sanjay J

    2017-03-29

    Animal models of depression repeatedly showed stress-induced nucleus accumbens (NAc) hypertrophy. Recently, ketamine was found to normalize this stress-induced NAc structural growth. Here, we investigated NAc structural abnormalities in major depressive disorder (MDD) in two cohorts. Cohort A included a cross-sectional sample of 34 MDD and 26 healthy control (HC) subjects, with high-resolution magnetic resonance imaging (MRI) to estimate NAc volumes. Proton MR spectroscopy ((1)H MRS) was used to divide MDD subjects into two subgroups: glutamate-based depression (GBD) and non-GBD. A separate longitudinal sample (cohort B) included 16 MDD patients who underwent MRI at baseline then 24 h following intravenous infusion of ketamine (0.5 mg/kg). In cohort A, we found larger left NAc volume in MDD compared to controls (Cohen's d=1.05), but no significant enlargement in the right NAc (d=0.44). Follow-up analyses revealed significant subgrouping effects on the left (d⩾1.48) and right NAc (d⩾0.95) with larger bilateral NAc in non-GBD compared to GBD and HC. NAc volumes were not different between GBD and HC. In cohort B, ketamine treatment reduced left NAc, but increased left hippocampal, volumes in patients achieving remission. The cross-sectional data provided the first evidence of enlarged NAc in patients with MDD. These NAc abnormalities were limited to patients with non-GBD. The pilot longitudinal data revealed a pattern of normalization of left NAc and hippocampal volumes particularly in patients who achieved remission following ketamine treatment, an intriguing preliminary finding that awaits replication.Neuropsychopharmacology advance online publication, 29 March 2017; doi:10.1038/npp.2017.49.

  19. Severity of depressive symptoms and accuracy of dietary reporting among obese women with major depressive disorder seeking weight loss treatment.

    PubMed

    Whited, Matthew C; Schneider, Kristin L; Appelhans, Bradley M; Ma, Yunsheng; Waring, Molly E; DeBiasse, Michele A; Busch, Andrew M; Oleski, Jessica L; Merriam, Philip A; Olendzki, Barbara C; Crawford, Sybil L; Ockene, Ira S; Lemon, Stephenie C; Pagoto, Sherry L

    2014-01-01

    An elevation in symptoms of depression has previously been associated with greater accuracy of reported dietary intake, however this association has not been investigated among individuals with a diagnosis of major depressive disorder. The purpose of this study was to investigate reporting accuracy of dietary intake among a group of women with major depressive disorder in order to determine if reporting accuracy is similarly associated with depressive symptoms among depressed women. Reporting accuracy of dietary intake was calculated based on three 24-hour phone-delivered dietary recalls from the baseline phase of a randomized trial of weight loss treatment for 161 obese women with major depressive disorder. Regression models indicated that higher severity of depressive symptoms was associated with greater reporting accuracy, even when controlling for other factors traditionally associated with reporting accuracy (coefficient  =  0.01 95% CI = 0.01 - 0.02). Seventeen percent of the sample was classified as low energy reporters. Reporting accuracy of dietary intake increases along with depressive symptoms, even among individuals with major depressive disorder. These results suggest that any study investigating associations between diet quality and depression should also include an index of reporting accuracy of dietary intake as accuracy varies with the severity of depressive symptoms.

  20. Major Depressive Disorder and Kappa Opioid Receptor Antagonists

    PubMed Central

    Li, Wei; Sun, Huijiao; Chen, Hao; Yang, Xicheng; Xiao, Li; Liu, Renyu; Shao, Liming; Qiu, Zhuibai

    2016-01-01

    Major depressive disorder (MDD) is a common psychiatric disease worldwide. The clinical use of tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs)/serotonin–norepinephrine reuptake inhibitor (SNRIs) for this condition have been widely accepted, but they were challenged by unacceptable side-effects, potential drug-drug interactions (DDIs) or slow onset/lack of efficacy. The endogenous opioid system is involved in stress and emotion regulatory processes and its role in MDD has been implicated. Although several KOR antagonists including JDTic and PF-04455242 were discontinued in early clinical trials, ALKS 5461 and CERC-501(LY-2456302) survived and entered into Phase-III and Phase-II trials, respectively. Considering the efficacy and safety of early off-label use of buprenorphine in the management of the treatment-resistant depression (TRD), it will be not surprising to predict the potential success of ALKS 5461 (a combination of buprenorphine and ALKS-33) in the near future. Moreover, CERC-501 will be expected to be available as monotherapy or adjuvant therapy with other first-line antidepressants in the treatment of TRD, if ongoing clinical trials continue to provide positive benefit-risk profiles. Emerging new researches might bring more drug candidates targeting the endogenous opioid system to clinical trials to address current challenges in MDD treatment in clinical practice. PMID:27213169

  1. Cognition as a target in major depression: new developments.

    PubMed

    Solé, Brisa; Jiménez, Esther; Martinez-Aran, Anabel; Vieta, Eduard

    2015-02-01

    Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric illness often accompanied of cognitive dysfunction which may persist even when patients achieve clinical remission. Currently, cognitive deficits emerge as a potential target because they compromise the functional outcome of depressed patients. The aim of this study was to review data for several potential pharmacological treatments targeting cognition in MDD, resulting from monotherapy or adjunctive treatment. An extensive and systematic Pubmed/Medline search of the published literature until March 2014 was conducted using a variety of search term to find relevant articles. Bibliographies of retrieved papers were further examined for publications of interest. Searches were limited to articles available in English language. We describe studies using modafinil, lisdexamfetamine, ketamine, lanicemine, memantine, galantamine, donepezil, vortioxetine, intranasal oxytocin, omega-3, s-adenosyl-methionine, scopolamine and erythropoietin. From these articles, we determined that there are a number of promising new therapies, pharmacological agents or complementary medicines, but data are just emerging. Drugs and therapies targeting cognitive dysfunction in MDD should prove effective in improving specific cognitive domains and functioning, while ruling out pseudospecificity.

  2. Vortioxetine: a review of its use in major depressive disorder.

    PubMed

    Garnock-Jones, Karly P

    2014-09-01

    Vortioxetine (Brintellix(®)) is a serotonin (5-HT) transporter inhibitor that also acts on several 5-HT receptors, such as the 5-HT3 and 5-HT1A receptors. It is approved in the US and the EU for the treatment of adult patients with major depressive disorder (MDD); this article reviews the pharmacological properties of oral vortioxetine and its clinical efficacy and tolerability in these patients. Vortioxetine is generally efficacious in patients with MDD in acute treatment trials (including elderly patients), in a relapse-prevention trial, and in open-label extension trials. It is associated with improved cognitive function in patients with MDD; this does not occur solely via improvement in depressive symptom severity. It is well tolerated, but is associated with significantly increased sexual dysfunction at the highest dosage; however, vortioxetine was shown to improve previous-treatment-emergent sexual dysfunction in patients with well-treated MDD to a greater degree than escitalopram. Vortioxetine extends the available treatment options for patients with MDD, and further investigation into its comparative efficacy versus other antidepressants will allow for more accurate placement among these treatment options.

  3. Folates and S-adenosylmethionine for major depressive disorder.

    PubMed

    Papakostas, George I; Cassiello, Clair F; Iovieno, Nadia

    2012-07-01

    Interest in nonpharmaceutical supplements for treating major depressive disorder (MDD) has increased significantly, both among patients and among clinicians during the past decades. Despite the large array of antidepressants (ADs) available, many patients continue to experience relatively modest response and remission rates, in addition to a burden of side effects that can hinder treatment compliance and acceptability. In this article, we review the literature on folates and S-adenosylmethionine (SAMe), 2 natural compounds linked in the 1-carbon cycle metabolic pathway, for which substantial evidence supports their involvement in mood disorders. Background information, efficacy data, proposed mechanisms of action, and side effects are reviewed. Based on existing data, supplementation with SAMe, as well as with various formulations of folates, appears to be efficacious and well tolerated in reducing depressive symptoms. Compared with other forms of folates, 5-methyltetrahydrofolate (L-methylfolate or 5-MTHF) may represent a preferable treatment option for MDD given its greater bioavailability in patients with a genetic polymorphism, and the lower risk of specific side effects associated with folic acid. Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium.

  4. Selegiline transdermal system: in the treatment of major depressive disorder.

    PubMed

    Frampton, James E; Plosker, Greg L

    2007-01-01

    The monamine oxidase (MAO) inhibitor selegiline is selective for MAO-B at the low oral dosages used in the treatment of Parkinson's disease. However, MAO-A is also inhibited at the high oral dosages needed to effectively treat depression (not an approved indication), necessitating a tyramine-restricted diet. The selegiline transdermal system was designed to deliver antidepressant drug concentrations to the CNS, without substantially impairing small intestine MAO-A activity. At the target dose of 6 mg/24 hours, tyramine dietary restrictions are not needed. Short-term treatment with fixed (6 mg/24 hours) or flexible (6, 9 or 12 mg/24 hours) doses of selegiline transdermal system was superior to placebo on most measures of antidepressant activity in 6- or 8-week, randomised, double-blind, multicentre studies in adult outpatients with major depressive disorder (MDD). Likewise, long-term treatment with a fixed dose of selegiline transdermal system 6 mg/24 hours was superior to placebo as maintenance therapy in a 52-week, randomised, double-blind, multicentre, relapse-prevention trial in patients with MDD. Selegiline transdermal system therapy was generally well tolerated in placebo-controlled studies; application site reactions, mostly of mild to moderate severity, were the most commonly reported adverse events. The incidence of sexual adverse effects and weight gain was low and similar to that with placebo.

  5. Biomarkers in major depressive disorder: the role of mass spectrometry.

    PubMed

    Woods, Alisa G; Iosifescu, Dan V; Darie, Costel C

    2014-01-01

    Major depressive disorder (MDD) is common. Despite numerous available treatments, many individuals fail to improve clinically. MDD continues to be diagnosed exclusively via behavioral rather than biological methods. Biomarkers-which include measurements of genes, proteins, and patterns of brain activity-may provide an important objective tool for the diagnosis of MDD or in the rational selection of treatments. Proteomic analysis and validation of its results as biomarkers is less explored than other areas of biomarker research in MDD. Mass spectrometry (MS) is a comprehensive, unbiased means of proteomic analysis, which can be complemented by directed protein measurements, such as Western Blotting. Prior studies have focused on MS analysis of several human biomaterials in MDD, including human post-mortem brain, cerebrospinal fluid (CSF), blood components, and urine. Further studies utilizing MS and proteomic analysis in MDD may help solidify and establish biomarkers for use in diagnosis, identification of new treatment targets, and understanding of the disorder. The ultimate goal is the validation of a biomarker or a biomarker signature that facilitates a convenient and inexpensive predictive test for depression treatment response and helps clinicians in the rational selection of next-step treatments.

  6. Peripheral biomarkers in animal models of major depressive disorder.

    PubMed

    Carboni, Lucia

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

  7. Heterogeneity of elderly depression: increased risk of Alzheimer's disease and Aβ protein metabolism.

    PubMed

    Namekawa, Yuki; Baba, Hajime; Maeshima, Hitoshi; Nakano, Yoshiyuki; Satomura, Emi; Takebayashi, Naoko; Nomoto, Hiroshi; Suzuki, Toshihito; Arai, Heii

    2013-06-03

    Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (<60 years) and late-onset (≥60years) MDD and controls. The results showed that the serum Aβ40/Aβ42 ratio was significantly higher in patients with both early- and late-onset MDD than in controls (early-onset, p=0.010; late-onset, p=0.043), and it is of great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD.

  8. The 5-HT1A receptor in Major Depressive Disorder

    PubMed Central

    Kaufman, Joshua; DeLorenzo, Christine; Choudhury, Sunia; Parsey, Ramin V.

    2016-01-01

    Major Depressive Disorder (MDD) is a highly prevalent psychiatric diagnosis that is associated with a high degree of morbidity and mortality. This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030. A large body of previous research has theorized that serotonergic dysfunction, specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD. The purpose of this review is to describe the evolution of our current understanding of the serotonin 1A (5-HT1A) receptor and its role in the pathophysiology MDD through the discussion of animal, post-mortem, positron emission tomography (PET), pharmacologic and genetic studies. PMID:26851834

  9. A Brain-Based Endophenotype for Major Depressive Disorder

    PubMed Central

    Peterson, Bradley S.; Weissman, Myrna M.

    2012-01-01

    We have identified a brain-based endophenotype for major depressive disorder (MDD) that includes thinning of the cortex of the lateral aspect of the right hemisphere and the medial aspect of the left, as well as bilateral hypoplasia of frontal and parietal white matter. The endophenotype status of these abnormalities is supported by their presence in a multi-generational cohort of persons who themselves do not have MDD but who are at increased familial risk for developing the illness. Those who have the endophenotype but who are not ill nevertheless still suffer from inattention and poor visual memory for social stimuli in direct proportion to the magnitude of cortical thinning and white matter hypoplasia within the endophenotype. Identification of this endophenotype and its cognitive correlates provides targets for devising new preventive and therapeutic interventions for MDD. PMID:21226617

  10. Desvenlafaxine succinate for the treatment of major depressive disorder.

    PubMed

    Lohoff, Falk W; Rickels, Karl

    2008-08-01

    Major depressive disorder (MDD) remains one of the most common psychiatric disorders with high morbidity and mortality. Effective treatment is limited and response/remission to antidepressant pharmacotherapy remains poor and unpredictable. The development of new antidepressants is thus of great importance to the field. Desvenlafaxine succinate (DVS) is the active metabolite of the serotonin and noradrenaline re-uptake inhibitor venlafaxine and was recently FDA approved for the treatment of MDD. DVS showed efficacy in clinical trials in MDD with doses ranging from 50 - 400 mg. Advantages compared to other antidepressants include once daily dosing at effective doses, no CYP450 metabolism and low drug-drug interactions. Concerns include side effect profile and moderate efficacy. DVS might be a useful addition to the arsenal of antidepressants available to the clinician. Additional studies, in particular head-to-head comparison to other antidepressants and long-term treatment studies, will be necessary to comprehensively evaluate DVS safety and efficacy for clinical practice.

  11. Molecular, Functional, and Structural Imaging of Major Depressive Disorder.

    PubMed

    Zhang, Kai; Zhu, Yunqi; Zhu, Yuankai; Wu, Shuang; Liu, Hao; Zhang, Wei; Xu, Caiyun; Zhang, Hong; Hayashi, Takuya; Tian, Mei

    2016-06-01

    Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD.

  12. The 5-HT1A receptor in Major Depressive Disorder.

    PubMed

    Kaufman, Joshua; DeLorenzo, Christine; Choudhury, Sunia; Parsey, Ramin V

    2016-03-01

    Major Depressive Disorder (MDD) is a highly prevalent psychiatric diagnosis that is associated with a high degree of morbidity and mortality. This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030. A large body of previous research has theorized that serotonergic dysfunction, specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD. The purpose of this review is to describe the evolution of our current understanding of the serotonin 1A (5-HT1A) receptor and its role in the pathophysiology MDD through the discussion of animal, post-mortem, positron emission tomography (PET), pharmacologic and genetic studies.

  13. Support Tool in the Diagnosis of Major Depressive Disorder

    NASA Astrophysics Data System (ADS)

    Nunes, Luciano Comin; Pinheiro, Plácido Rogério; Pequeno, Tarcísio Cavalcante; Pinheiro, Mirian Calíope Dantas

    Major Depressive Disorder have been responsible for millions of professionals temporary removal, and even permanent, from diverse fields of activities around the world, generating damage to social, financial, productive systems and social security, and especially damage to the image of the individual and his family that these disorders produce in individuals who are patients, characteristics that make them stigmatized and discriminated into their society, making difficult their return to the production system. The lack of early diagnosis has provided reactive and late measures, only when the professional suffering psychological disorder is already showing signs of incapacity for working and social relationships. This article aims to assist in the decision making to establish early diagnosis of these types of psychological disorders. It presents a proposal for a hybrid model composed of expert system structured methodologies for decision support (Multi-Criteria Decision Analysis - MCDA) and representations of knowledge structured in logical rules of production and probabilities (Artificial Intelligence - AI).

  14. Sheehan’s Syndrome Presenting as Major Depressive Disorder

    PubMed Central

    Qadri, Mehmood I; Mushtaq, Mohsin Bin; Qazi, Iram; Yousuf, Sameena; Rashid, Aaliya

    2015-01-01

    Sheehan’s syndrome or Simmond’s disease is a rare endocrine disorder seen in clinical practice. The clinical spectrum is diverse and a high index of suspicion together with a good clinical acumen and proper diagnostic approach helps in early diagnosis and prompt treatment of this endocrinopathy. Sheehan’s syndrome presenting as a major depressive disorder finds less mention in the literature. The patient discussed here is a 45-year-old female who had been on antidepressants and psychiatry follow up for a long time until she presented to our Out Patient Department (OPD), where she was evaluated in detail and diagnosed as a case of Sheehan’s syndrome. The patient is doing well and is on a regular follow-up with us. Further studies are required to demystify the strength of this association in more detail and to elucidate the possible underlying mechanism. PMID:25648343

  15. Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites

    SciTech Connect

    Comellas Canal, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-08-26

    Alpha-Synuclein (AS) fibrils constitute the major proteinaceous component of Lewy bodies (LBs), the pathological hallmark of Parkinson’s disease (PD) and other neurodegenerative diseases. Three single point mutations in the AS gene, as well as multiplication of the wild-type (WT) AS allele, have been previously identified in families with early-onset PD. Although AS fibrils have been the subject of intense study, critical details about their structure including the precise location of the B-strands and the extent of the core, the three-dimensional structure and the effects of the mutations—remain unknown. Here, we have used magic-angle spinning solid-state NMR spectroscopy to present a detailed characterization of the full-length WT AS fibrils. With improved sample preparations, isotopic labeling patterns and NMR experiments, we have confidently assigned more than 90% of the 13C and 15N backbone and sidechain chemical shifts of the detected residues from residue 39 to 97, and quantified the conformational dynamics throughout this region. Our results demonstrate that the core of AS fibrils extends with a repeated motif and that residues 30, 46 and 53-the early-onset PD mutant sites-are located in structured regions of AS fibrils.

  16. Intimate partner violence against adult women and its association with major depressive disorder, depressive symptoms and postpartum depression: a systematic review and meta-analysis.

    PubMed

    Beydoun, Hind A; Beydoun, May A; Kaufman, Jay S; Lo, Bruce; Zonderman, Alan B

    2012-09-01

    To date, few systematic reviews of observational studies have been conducted to comprehensively evaluate the co-morbidity of intimate partner violence (IPV) and specific depression outcomes in women. In this systematic review and meta-analysis, we summarize the extant literature and estimate the magnitude of the association between IPV and key depressive outcomes (elevated depressive symptoms, diagnosed major depressive disorder and postpartum depression). PubMed (January 1, 1980-December 31, 2010) searches of English-language observational studies were conducted. Most of the selected 37 studies had cross-sectional population-based designs, focused on elevated depressive symptoms and were conducted in the United States. Most studies suggested moderate or strong positive associations between IPV and depression. Our meta-analysis suggested two to three-fold increased risk of major depressive disorder and 1.5-2-fold increased risk of elevated depressive symptoms and postpartum depression among women exposed to intimate partner violence relative to non-exposed women. A sizable proportion (9%-28%) of major depressive disorder, elevated depressive symptoms, and postpartum depression can be attributed to lifetime exposure to IPV. In an effort to reduce the burden of depression, continued research is recommended for evaluating IPV preventive strategies.

  17. An altered peripheral IL6 response in major depressive disorder.

    PubMed

    Money, Kelli M; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A; Shelton, Richard C; Mirnics, Karoly

    2016-05-01

    Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in

  18. Major depression in mothers predict reduced ventral striatum activation in adolescent female offspring with and without depression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder. However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for major depressive ...

  19. Cognitive-Behavioral Therapy of Panic Disorder with Secondary Major Depression: A Preliminary Investigation.

    ERIC Educational Resources Information Center

    Laberge, Benoit; And Others

    1993-01-01

    Investigated extent to which cognitive-behavioral therapy can be used successfully in treatment of secondary depressed panic patients. Findings from eight panic patients with major depression and seven panic patients without major depression showed that cognitive-behavioral therapy was significantly superior to information-based therapy in…

  20. Tianeptine in combination with monoamine oxidase inhibitors for major depressive disorder.

    PubMed

    Tobe, Edward H

    2012-10-09

    Major depressive disorder may respond to monotherapy with monoamine oxidase inhibitors (MAOIs) or tianeptine. Literature search showed no reports of MAOIs combined with tianeptine. The method included was clinical case history. A 59-year-old woman had partial improvement of depression with the MAOI tranylcypromine combined with topiramate, trazodone and ziprasidone. The patient had further improvement of depression symptoms after addition of tianeptine. No adverse events were evident. The combination of MAIOs and tianeptine may be effective for refractory major depressive disorder.

  1. Bias to negative emotions: a depression state-dependent marker in adolescent major depressive disorder.

    PubMed

    Maalouf, Fadi T; Clark, Luke; Tavitian, Lucy; Sahakian, Barbara J; Brent, David; Phillips, Mary L

    2012-06-30

    The aim of the current research was to examine for the first time the extent to which bias to negative emotions in an inhibitory control paradigm is a state or trait marker in major depressive disorder (MDD) in adolescents. We administered the affective go/no go task which measures the ability to switch attention to or away from positive or negative emotional stimuli to 40 adolescents with MDD (20 in acute episode (MDDa) and 20 in remission (MDDr)) and 17 healthy controls (HC). MDDa were significantly faster on the shift to negative target blocks as compared to shift to positive target blocks while HC and MDDr displayed the opposite pattern as measured by an "emotional bias index" (EBI=latency (shift to negative targets)-latency (shift to positive targets)). There was also a trend for an effect of group on commission errors, suggesting more impulsive responding by MDDa than both MDDr and HC independently of stimulus valence throughout the task. Negative bias was not associated with depression severity or medication status. In conclusion, bias to negative emotional stimuli appears to be present in the acute stage of MDD and absent in remission suggesting that it is a depression state-specific marker of MDD in adolescents. Latency emerges as a better proxy of negative bias than commission errors and accuracy on this inhibitory control task in adolescents with MDD.

  2. Rediscovering trazodone for the treatment of major depressive disorder.

    PubMed

    Fagiolini, Andrea; Comandini, Alessandro; Catena Dell'Osso, Mario; Kasper, Siegfried

    2012-12-01

    Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as Oleptro™; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the management of patients with MDD. Although trazodone is approved for the treatment of depression, evidence supports the use of low-dose trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as

  3. A novel urinary metabolite signature for diagnosing major depressive disorder.

    PubMed

    Zheng, Peng; Chen, Jian-jun; Huang, Ting; Wang, Ming-ju; Wang, Ying; Dong, Mei-xue; Huang, Yuan-jun; Zhou, Lin-ke; Xie, Peng

    2013-12-06

    Major depressive disorder (MDD) is a prevalent and debilitating mental disorder. Yet, there are no objective biomarkers available to support diagnostic laboratory testing for this disease. Here, gas chromatography-mass spectrometry was applied to urine metabolic profiling of 126 MDD and 134 control subjects. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to identify the differential metabolites in MDD subjects relative to healthy controls. The OPLS-DA analysis of data from training samples (82 first-episode, drug-naïve MDD subjects and 82 well-matched healthy controls) showed that the depressed group was significantly distinguishable from the control group. Totally, 23 differential urinary metabolites responsible for the discrimination between the two groups were identified. Postanalysis, 6 of the 23 metabolites (sorbitol, uric acid, azelaic acid, quinolinic acid, hippuric acid, and tyrosine) were defined as candidate diagnostic biomarkers for MDD. Receiver operating characteristic analysis of combined levels of these six biomarkers yielded an area under the receiver operating characteristic curve (AUC) of 0.905 in distinguishing training samples; this simplified metabolite signature classified blinded test samples (44 MDD subjects and 52 healthy controls) with an AUC of 0.837. Furthermore, a composite panel by the addition of previously identified urine biomarker (N-methylnicotinamide) to this biomarker panel achieved a more satisfactory accuracy, yielding an AUC of 0.909 in the training samples and 0.917 in the test samples. Taken together, these results suggest this composite urinary metabolite signature should facilitate development of a urine-based diagnostic test for MDD.

  4. 'Hot' cognition in major depressive disorder: a systematic review.

    PubMed

    Miskowiak, Kamilla W; Carvalho, Andre F

    2014-01-01

    Major depressive disorder (MDD) is associated with significant cognitive dysfunction in both 'hot' (i.e. emotion-laden) and 'cold' (non-emotional) domains. Here we review evidence pertaining to 'hot' cognitive changes in MDD. This systematic review searched the PubMed and PsycInfo computerized databases in May 2014 augmented by hand searches of reference lists. We included original articles in which MDD participants (or their healthy first-degree relatives) and a healthy control group were compared on standard measures of emotional processing or reward/ punishment processing as well as systematic reviews and meta-analyses. A total of 116 articles met the inclusion criteria of which 97 were original studies. Negative biases in perception, attention and memory for emotional information, and aberrant reward/punishment processing occur in MDD. Imbalanced responses to negative stimuli in a fronto-limbic network with hyper-activity in limbic and ventral prefrontal regions paired with hypo-activity of dorsal prefrontal regions subserve these abnormalities. A cross-talk of 'hot' and 'cold' cognition disturbances in MDD occurs. Disturbances in 'hot cognition' may also contribute to the perpetuation of negative emotional states in MDD. Limited success in the identification of susceptibility genes in MDD has led to great research interest in identifying vulnerability biomarkers or endophenotypes. Emerging evidence points to the persistence of 'hot' cognition dysfunction during remission and to subtle 'hot' cognition deficits in healthy relatives of patients with MDD. Taken together, these findings suggest that abnormalities in 'hot' cognition may constitute a candidate neurocognitive endophenotype for depression.

  5. Social relationship correlates of major depressive disorder and depressive symptoms in Switzerland: nationally representative cross sectional study

    PubMed Central

    2014-01-01

    Background The quality and quantity of social relationships are associated with depression but there is less evidence regarding which aspects of social relationships are most predictive. We evaluated the relative magnitude and independence of the association of four social relationship domains with major depressive disorder and depressive symptoms. Methods We analyzed a cross-sectional telephone interview and postal survey of a probability sample of adults living in Switzerland (N = 12,286). Twelve-month major depressive disorder was assessed via structured interview over the telephone using the Composite International Diagnostic Interview (CIDI). The postal survey assessed depressive symptoms as well as variables representing emotional support, tangible support, social integration, and loneliness. Results Each individual social relationship domain was associated with both outcome measures, but in multivariate models being lonely and perceiving unmet emotional support had the largest and most consistent associations across depression outcomes (incidence rate ratios ranging from 1.55-9.97 for loneliness and from 1.23-1.40 for unmet support, p’s < 0.05). All social relationship domains except marital status were independently associated with depressive symptoms whereas only loneliness and unmet support were associated with depressive disorder. Conclusions Perceived quality and frequency of social relationships are associated with clinical depression and depressive symptoms across a wide adult age spectrum. This study extends prior work linking loneliness to depression by showing that a broad range of social relationship domains are associated with psychological well-being. PMID:24656048

  6. The Relationship of Undergraduate Major and Housing with Depression in Undergraduate Students

    PubMed Central

    Schaus, James F; Deichen, Michael

    2016-01-01

    Introduction: Past literature has shown that college undergraduates are particularly vulnerable to depression. The objective of this study is to find if certain majors and housing arrangements are associated with major depression as assessed by the Patient Health Questionnaire (PHQ-9), after adjustment for age, gender, and family history of depression. Methods: Participants were undergraduates at a large public university that used the university health center from April 1 - November 4, 2013. Participants completed a survey which included the PHQ-2, a validated screening test for depression. Those who scored positive were asked to take the longer PHQ-9 survey to assess for major depression. Logistic regression was used to test the significance of associations between several prescribed variables (namely, college major, housing arrangement, age, gender, and family history of depression) and outcome (major depression as assessed by the PHQ-9). Results: Of 541 students, 71 (13.1%) scored positive on the PHQ-9 for depression. Family history was significantly associated (OR 4.20, 95% CI, 2.42, 7.29) with major depressive disorder, as was a major in the College of Arts and Humanities (OR 3.84, 95% CI, 1.18, 12.46) compared to the baseline of an undecided/interdisciplinary major. Conclusions: A major in the College of Arts and Humanities was significantly associated with major depression. This may be significant for future efforts to target mental health interventions on college campuses. PMID:27900233

  7. The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder

    PubMed Central

    Evans, Kenneth R.; Kalali, Amir H.; Kennedy, Sidney H.; Engelhardt, Nina; Frey, Benicio N.; Greist, John H.; Kobak, Kenneth A.; Lam, Raymond W.; MacQueen, Glenda; Milev, Roumen; Placenza, Franca M.; Ravindran, Arun V.; Sheehan, David V.; Sills, Terrence; Williams, Janet B.W.

    2016-01-01

    The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well. PMID:27974997

  8. The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

    PubMed

    Vaccarino, Anthony L; Evans, Kenneth R; Kalali, Amir H; Kennedy, Sidney H; Engelhardt, Nina; Frey, Benicio N; Greist, John H; Kobak, Kenneth A; Lam, Raymond W; MacQueen, Glenda; Milev, Roumen; Placenza, Franca M; Ravindran, Arun V; Sheehan, David V; Sills, Terrence; Williams, Janet B W

    2016-01-01

    The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.

  9. The interrelation between premenstrual syndrome and major depression: Results from a population-based sample

    PubMed Central

    2011-01-01

    Background Research about the relationship between premenstrual syndrome (PMS) and major depression is limited. This study examined the relationship between moderate to severe PMS and major depression in a population-based sample of women of reproductive age. The objectives of the study were to assess the association between premenstrual syndrome and major depression, to analyse how PMS and major depression differ and to characterise the group of women who report both PMS and major depression. Methods Data were obtained from the Swiss Health Survey 2007. Included in the analysis was data from women under the age of 55 without hysterectomy and who answered the questions on PMS symptoms. The population-based sample consisted of 3518 women. Weighted prevalence rates were calculated and relative risk ratios for PMS, major depression and women who reported both PMS and major depression, were calculated with logistic multinominal logit regression. Results The prevalence of major depression was 11.3% in women screening positive for moderate PMS and 24.6% in women screening positive for severe PMS. Compared to women without any of these conditions, women who reported moderate to severe alcohol consumption had a lower risk for PMS. Women reporting use of antidepressants, and use of oral contraceptives had a higher risk for major depression compared to women without any of these conditions. Women reporting work dissatisfaction had a higher risk for PMS. A higher relative risk to report both PMS and major depression compared to women without PMS or major depression was related to factors such as high psychological distress, low mastery, psychotropic drug consumption, and low self-rated health. Conclusions The results suggested that women who suffer from both PMS and major depression are more impaired compared to women with only one disorder. The results further indicated that PMS and major depression are different disorders that can, however, co-occur. PMID:21992230

  10. Mania and depression in the perinatal period among women with a history of major depressive disorders

    PubMed Central

    Inglis, Angela J; Hippman, Catriona L; Carrion, Prescilla B; Honer, William G; Austin, Jehannine C

    2014-01-01

    Background Women with a history of major depressive disorder (MDD) have increased risks for postpartum depression, but less is known about postpartum mania in this population. Objectives To prospectively determine the frequency with which mania occurs in the postpartum among women who have a history of MDD, and to explore temporal relationships between onset of mania/hypomania and depression. Methods We administered the Structured Clinical Interview for DSM IV disorders (SCID) to pregnant women with a self-reported history of MDD to confirm diagnosis and exclude women with any history of mania/hypomania. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) and Altman Self-Rated Mania scale (ASRM): once during the pregnancy (~26 weeks), and one week, one month, and three months postpartum. Results Among women (N=107) with a SCID-confirmed diagnosis of MDD, 34.6% (n=37) experienced mania/hypomania (defined by an ASRM score of ≥6) at ≥1 timepoint during the postpartum: and for just over half (20/37, 54%), onset was during the postpartum. The highest frequency of mania/hypomania (26.4%, n=26) was at one week postpartum. Women who experienced mania/hypomania at one week postpartum had significantly more symptoms of mania/hypomania later in the postpartum. Conclusion A substantive proportion of women with a history of MDD may experience first onset of mania/hypomania symptoms in the early postpartum, others may experience first onset during pregnancy. Taken with other recent data, these findings suggest a possible rationale for screening women with a history of MDD for mania/hypomania during the early postpartum period, but issues with screening instruments are discussed. PMID:24402681

  11. Mania and depression in the perinatal period among women with a history of major depressive disorders.

    PubMed

    Inglis, Angela J; Hippman, Catriona L; Carrion, Prescilla B; Honer, William G; Austin, Jehannine C

    2014-04-01

    Women with a history of major depressive disorder (MDD) have increased risks for postpartum depression, but less is known about postpartum mania in this population. The objectives of this study were to prospectively determine the frequency with which mania occurs in the postpartum among women who have a history of MDD and to explore temporal relationships between onset of mania/hypomania and depression. We administered the Structured Clinical Interview for DSM IV disorders (SCID) to pregnant women with a self-reported history of MDD to confirm diagnosis and exclude women with any history of mania/hypomania. Participants completed the Edinburgh Postnatal Depression Scale and Altman Self-Rating Mania Scale (ASRM) once during the pregnancy (∼26 weeks) and 1 week, 1 month, and 3 months postpartum. Among women (n = 107) with a SCID-confirmed diagnosis of MDD, 34.6 % (n = 37) experienced mania/hypomania (defined by an ASRM score of ≥6) at ≥1 time point during the postpartum, and for just over half (20/37, 54 %), onset was during the postpartum. The highest frequency of mania/hypomania (26.4 %, n = 26) was at 1 week postpartum. Women who experienced mania/hypomania at 1 week postpartum had significantly more symptoms of mania/hypomania later in the postpartum. A substantive proportion of women with a history of MDD may experience first onset of mania/hypomania symptoms in the early postpartum, others may experience first onset during pregnancy. Taken with other recent data, these findings suggest a possible rationale for screening women with a history of MDD for mania/hypomania during the early postpartum period, but issues with screening instruments are discussed.

  12. Influence of smoking and race on immunoglobulin G subclass concentrations in early-onset periodontitis patients.

    PubMed Central

    Quinn, S M; Zhang, J B; Gunsolley, J C; Schenkein, J G; Schenkein, H A; Tew, J G

    1996-01-01

    Recent data indicate that smoking is an important risk factor for the development of periodontitis. Smoking is also known to reduce serum immunoglobulin G (IgG) levels. Interestingly, patients with the localized form of early-onset periodontitis (LJP) have elevated levels of serum IgG2, and those who smoke are not clinically different from nonsmoking LJ subjects. In contrast, patients with the generalized form of early-onset periodontitis (G-EOP) who smoke have more extensive destruction than their nonsmoking counterparts. Given the effects of smoking on EOP and the association of IgG2 with less severe disease, we hypothesized that smoking might reduce serum IgG2 and that this might be most apparent in G-EOP. We therefore examined the effects of smoking on serum IgG subclass concentrations in race-matched groups: LJP, G-EOP, and age-matched periodontally healthy controls (NPs). Smoking status was established from serum cotinine levels, and serum IgG subclass concentrations were determined by using radial immunodiffusion. The data indicated that the effects of smoking were remarkably selective with respect to both IgG subclass and race. Smoking did not appear to have any effect on the concentration of IgG1 or IgG3 in either black or white subjects. In contrast, smoking was associated with depressed serum IgG2 concentrations in both white NP and G-EOP subgroups. Serum IgG2 levels in black subjects did not appear to be depressed by smoking, with the single striking exception of the black G-EOP subgroup which also had depressed serum IgG4 levels. The results here confirm that smoking has effects on serum immunoglobulin levels, but the effects were both race and serum IgG subclass specific. Furthermore, the periodontal diagnosis of EOP subjects appeared to be important, as indicated by the fact that IgG2 and IgG4 levels were reduced in smoking black G-EOP subjects whereas the IgG2 and IgG4 levels in black LJP and NP subjects were not reduced by smoking. PMID:8698472

  13. Major depressive disorder viewed as a dysfunction in astroglial bioenergetics.

    PubMed

    Hundal, Øivind

    2007-01-01

    For many years scientists and physicians have pondered upon the apparent connection between depressive disorder and diabetes mellitus. Several epidemiologic studies confirm that diabetics have increased incidence of depression, and vice versa. In addition: depressive, non-diabetic patients have several insulin- and glucose-metabolism disturbances, probably exerting a compensatory reaction to the malfunction in the depressed brain as these disturbances are normalised in remission. After the discovery of PET-scanning, such studies have shown that patients with depressive disorder have reduced glucose metabolism in frontal parts of the brain. The present hypothesis regards the PET findings as observations of the primary pathophysiology of depression. Furthermore: two studies of post mortem samples from depressed patients show reduced numbers of astroglia. This is in accordance to the mentioned insulin disturbances, as only astroglia, not neurons, have insulin-sensitive glucose metabolism. Hence: the astroglia, not necessarily the neurons, are proposed to be the type of cells in which the disease resides. Most probably depressive disorder is a multitude of diseases, explaining the apparent multitude of symptoms, and the fact that different patients do respond to different drugs. Therefore: one can only formulate the hypothesis by mentioning a common denominator to these specific malfunctions, namely: disturbed glucose metabolism in the depressed brain. The present paper reviews several findings and proposes that attenuated cerebral glucose metabolism in frontal parts of the brain, in the astroglia, is the cause of depressive disorder.

  14. Effects of major depression on the cognitive function of younger and older subjects.

    PubMed

    Tarbuck, A F; Paykel, E S

    1995-03-01

    The effects of age and depression on cognitive function were investigated in two groups of in-patient major depressives aged under and over 60 years who were tested when depressed and after recovery. The majority of the tests showed impaired performance during depression with improvement after recovery, and also differences between the two age-groups in both the depressed and recovered phases. However, the older subjects were not more severely affected by depression than the younger subjects. The pattern of impairment associated with depression was different to that associated with older age: depression affected performance on more 'complex tasks', whereas age was associated particularly with slowing on timed tests. This study did not suggest that the impairment from baseline due to the depression is greater in the elderly than in younger subjects.

  15. Neuronal correlates of facial emotion discrimination in early onset schizophrenia.

    PubMed

    Seiferth, Nina Y; Pauly, Katharina; Kellermann, Thilo; Shah, N Jon; Ott, Gudrun; Herpertz-Dahlmann, Beate; Kircher, Tilo; Schneider, Frank; Habel, Ute

    2009-01-01

    Emotion discrimination deficits represent a well-established finding in schizophrenia. Although imaging studies addressed the cerebral dysfunctions underlying emotion perception in adult patients, the question of trait vs state characteristics is still unresolved. The investigation of juvenile patients offers the advantage of studying schizophrenia at an age where influences of illness course and long-term medication are minimized. This may enable a more detailed characterization of emotion discrimination impairments and their cerebral correlates with respect to their appearance and exact nature. A total of 12 juvenile patients with early onset schizophrenia and matched healthy juveniles participated in this study. fMRI data were acquired during an emotion discrimination task consisting of standardized photographs of faces displaying happy, sad, angry, fearful, or neutral facial expression. Similar to findings in adult patients, juvenile patients exhibited reduced performance specificity whereas sensitivity was unaffected. Independent of the valence, their processing of emotional faces was associated with hypoactivations in both fusiform gyri and in the left inferior occipital gyrus. In addition, hyperactivations in patients were found in the right cuneus common to happy, angry, and fearful faces. Further, most distinct changes were present in juvenile patients when processing sad faces. These results point to a dysfunction in cerebral circuits relevant for emotion processing already prominent in adolescent schizophrenia patients. Regions affected by a decrease in activation are related to visual and face processing, similar to deficits reported in adult patients. These changes are accompanied by hyperactivations in areas related to emotion regulation and attribution, possibly reflecting compensatory mechanisms.

  16. Early-onset dementias: diagnostic and etiological considerations

    PubMed Central

    2013-01-01

    This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

  17. Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion.

    PubMed

    Allen, Nicholas M; Conroy, Judith; Shahwan, Amre; Lynch, Bryan; Correa, Raony G; Pena, Sergio D J; McCreary, Dara; Magalhães, Tiago R; Ennis, Sean; Lynch, Sally A; King, Mary D

    2016-01-01

    Early onset epileptic encephalopathies (EOEEs) represent a significant diagnostic challenge. Newer genomic approaches have begun to elucidate an increasing number of responsible single genes as well as emerging diagnostic strategies. In this single-center study, we aimed to investigate a cohort of children with unexplained EOEE. We performed whole-exome sequencing (WES), targeting a list of 137 epilepsy-associated genes on 50 children with unexplained EOEE. We characterized all phenotypes in detail and classified children according to known electroclinical syndromes where possible. Infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We identified disease-causing variants in 11 children (22%) in the following genes: STXBP1 (n = 3), KCNB1 (n = 2), KCNT1, SCN1A, SCN2A, GRIN2A, DNM1, and KCNA2. We also identified two further variants (in GRIA3 and CPA6) in two children requiring further investigation. Eleven variants were de novo, and in one paternal testing was not possible. Phenotypes were broadened for some variants identified. This study demonstrates that WES is a clinically useful screening tool for previously investigated unexplained EOEE and allows for reanalysis of data as new genes are being discovered. Detailed phenotyping allows for expansion of specific gene disorders leading to epileptic encephalopathy and emerging sub-phenotypes.

  18. TYROBP genetic variants in early-onset Alzheimer's disease.

    PubMed

    Pottier, Cyril; Ravenscroft, Thomas A; Brown, Patricia H; Finch, NiCole A; Baker, Matt; Parsons, Meeia; Asmann, Yan W; Ren, Yingxue; Christopher, Elizabeth; Levitch, Denise; van Blitterswijk, Marka; Cruchaga, Carlos; Campion, Dominique; Nicolas, Gaël; Richard, Anne-Claire; Guerreiro, Rita; Bras, Jose T; Zuchner, Stephan; Gonzalez, Michael A; Bu, Guojun; Younkin, Steven; Knopman, David S; Josephs, Keith A; Parisi, Joseph E; Petersen, Ronald C; Ertekin-Taner, Nilüfer; Graff-Radford, Neill R; Boeve, Bradley F; Dickson, Dennis W; Rademakers, Rosa

    2016-12-01

    We aimed to identify new candidate genes potentially involved in early-onset Alzheimer's disease (EOAD). Exome sequencing was conducted on 45 EOAD patients with either a family history of Alzheimer's disease (AD, <65 years) or an extremely early age at the onset (≤55 years) followed by multiple variant filtering according to different modes of inheritance. We identified 29 candidate genes potentially involved in EOAD, of which the gene TYROBP, previously implicated in AD, was selected for genetic and functional follow-up. Using 3 patient cohorts, we observed rare coding TYROBP variants in 9 out of 1110 EOAD patients, whereas no such variants were detected in 1826 controls (p = 0.0001), suggesting that at least some rare TYROBP variants might contribute to EOAD risk. Overexpression of the p.D50_L51ins14 TYROBP mutant led to a profound reduction of TREM2 expression, a well-established risk factor for AD. This is the first study supporting a role for genetic variation in TYROBP in EOAD, with in vitro support for a functional effect of the p.D50_L51ins14 TYROBP mutation on TREM2 expression.

  19. Abnormal temporal difference reward-learning signals in major depression.

    PubMed

    Kumar, P; Waiter, G; Ahearn, T; Milders, M; Reid, I; Steele, J D

    2008-08-01

    Anhedonia is a core symptom of major depressive disorder (MDD), long thought to be associated with reduced dopaminergic function. However, most antidepressants do not act directly on the dopamine system and all antidepressants have a delayed full therapeutic effect. Recently, it has been proposed that antidepressants fail to alter dopamine function in antidepressant unresponsive MDD. There is compelling evidence that dopamine neurons code a specific phasic (short duration) reward-learning signal, described by temporal difference (TD) theory. There is no current evidence for other neurons coding a TD reward-learning signal, although such evidence may be found in time. The neuronal substrates of the TD signal were not explored in this study. Phasic signals are believed to have quite different properties to tonic (long duration) signals. No studies have investigated phasic reward-learning signals in MDD. Therefore, adults with MDD receiving long-term antidepressant medication, and comparison controls both unmedicated and acutely medicated with the antidepressant citalopram, were scanned using fMRI during a reward-learning task. Three hypotheses were tested: first, patients with MDD have blunted TD reward-learning signals; second, controls given an antidepressant acutely have blunted TD reward-learning signals; third, the extent of alteration in TD signals in major depression correlates with illness severity ratings. The results supported the hypotheses. Patients with MDD had significantly reduced reward-learning signals in many non-brainstem regions: ventral striatum (VS), rostral and dorsal anterior cingulate, retrosplenial cortex (RC), midbrain and hippocampus. However, the TD signal was increased in the brainstem of patients. As predicted, acute antidepressant administration to controls was associated with a blunted TD signal, and the brainstem TD signal was not increased by acute citalopram administration. In a number of regions, the magnitude of the abnormal

  20. Automaticity in Anxiety Disorders and Major Depressive Disorder

    PubMed Central

    Teachman, Bethany A.; Joormann, Jutta; Steinman, Shari; Gotlib, Ian H.

    2012-01-01

    In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is not sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation. PMID:22858684

  1. Perceived parenting and risk for major depression in Chinese women

    PubMed Central

    Gao, J.; Li, Y.; Cai, Y.; Chen, J.; Shen, Y.; Ni, S.; Wei, Y.; Qiu, Y.; Zhu, X.; Liu, Y.; Lu, C.; Chen, C.; Niu, Q.; Tang, C.; Yang, Y.; Wang, Q.; Cui, W.; Xia, J.; Liu, T.; Zhang, J.; Zhao, B.; Guo, Z.; Pan, J.; Chen, H.; Luo, Y.; Sun, L.; Xiao, X.; Chen, Q.; Zhao, X.; He, F.; Lv, L.; Guo, L.; Liu, L.; Li, H.; Shi, S.; Flint, J.; Kendler, K. S.; Tao, M.

    2012-01-01

    Background In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China? Method Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview. Results Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD. Conclusions Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD. PMID:21943491

  2. Urinary peptidomics identifies potential biomarkers for major depressive disorder.

    PubMed

    Wang, Ying; Chen, Jianjun; Chen, Liang; Zheng, Peng; Xu, Hong-Bo; Lu, Jia; Zhong, Jiaju; Lei, Yang; Zhou, Chanjuan; Ma, Qingwei; Li, Yan; Xie, Peng

    2014-06-30

    Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD.

  3. cGMP Signaling, Phosphodiesterases and Major Depressive Disorder

    PubMed Central

    Reierson, Gillian W; Guo, Shuyu; Mastronardi, Claudio; Licinio, Julio; Wong, Ma-Li

    2011-01-01

    Deficits in neuroplasticity are hypothesized to underlie the pathophysiology of major depressive disorder (MDD): the effectiveness of antidepressants is thought to be related to the normalization of disrupted synaptic transmission and neurogenesis. The cyclic adenosine monophosphate (cAMP) signaling cascade has received considerable attention for its role in neuroplasticity and MDD. However components of a closely related pathway, the cyclic guanosine monophosphate (cGMP) have been studied with much lower intensity, even though this signaling transduction cascade is also expressed in the brain and the activity of this pathway has been implicated in learning and memory processes. Cyclic GMP acts as a second messenger; it amplifies signals received at postsynaptic receptors and activates downstream effector molecules resulting in gene expression changes and neuronal responses. Phosphodiesterase (PDE) enzymes degrade cGMP into 5’GMP and therefore they are involved in the regulation of intracellular levels of cGMP. Here we review a growing body of evidence suggesting that the cGMP signaling cascade warrants further investigation for its involvement in MDD and antidepressant action. PMID:22654729

  4. Targeting the Glutamatergic System to Treat Major Depressive Disorder

    PubMed Central

    Mathews, Daniel C.; Henter, Ioline D.; Zarate, Carlos A.

    2012-01-01

    Major depressive disorder (MDD) is a severe, debilitating medical illness that affects millions of individuals worldwide. The young age of onset and chronicity of the disorder has a significant impact on the long-term disability that affected individuals face. Most existing treatments have focused on the ‘monoamine hypothesis’ for rational design of compounds. However, patients continue to experience low remission rates, residual subsyndromal symptoms, relapses and overall functional impairment. In this context, growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of MDD, and discuss the efficacy of glutamatergic agents as novel therapeutics. Preliminary clinical evidence has been promising, particularly with regard to the N-methyl-D-aspartate (NMDA) antagonist ketamine as a ‘proof-of-concept’ agent. The review also highlights potential molecular and inflammatory mechanisms that may contribute to the rapid antidepressant response seen with ketamine. Because existing pharmacological treatments for MDD are often insufficient for many patients, the next generation of treatments needs to be more effective, rapid acting and better tolerated than currently available medications. There is extant evidence that the glutamatergic system holds considerable promise for developing the next generation of novel and mechanistically distinct agents for the treatment of MDD. PMID:22731961

  5. Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

    PubMed Central

    Li, Gang; Fralick, Drew; Shen, Ting; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang; Fang, Yiru

    2015-01-01

    Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process. PMID:25793287

  6. Major depressive disorder and diabetes: does serotonin bridge the gap?

    PubMed

    De Long, Nicole E; Stepita, Rebecca A; Taylor, Valerie H; Holloway, Alison C

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of MDD and this system is the primary focus of most medications used in the treatment of illness. Although antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.

  7. Antidepressants versus placebo in major depression: an overview

    PubMed Central

    Khan, Arif; Brown, Walter A

    2015-01-01

    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. PMID:26407778

  8. Depressive symptoms and major depressive disorder in patients affected by subclinical hypothyroidism: a cross-sectional study.

    PubMed

    Demartini, Benedetta; Ranieri, Rebecca; Masu, Annamaria; Selle, Valerio; Scarone, Silvio; Gambini, Orsola

    2014-08-01

    The relationship between subclinical hypothyroidism and depression is still controversial. Our objective was to compare the prevalence of depressive symptoms and major depressive disorder in a population of patients affected by subclinical hypothyroidism and a control group without thyroid disease. The authors enrolled 123 consecutive outpatients affected by subclinical hypothyroidism undergoing follow-up at the endocrinology department of San Paolo Hospital in Milan and 123 controls without thyroid disease under the charge of general physicians.All patients and controls underwent an evaluation by means of a psychiatric interview; Hamilton Rating Scale for Depression (HAM-D); Montgomery-Asberg Depression Rating Scale (MADRS); and serum thyroid stimulating hormone, free T4, and free T3 levels. Patients were also screened for thyroid peroxidase antibodies and thyroglobulin antibodies. Patients affected by subclinical hypothyroidism had a prevalence of depressive symptoms of 63.4% at HAM-D and 64.2% at MADRS; 22 patients (17.9%) had a diagnosis of depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria). The control group had a prevalence of depressive symptoms of 27.6% at HAM-D and 29.3% at MADRS, and only seven controls had a diagnosis of depressive episode. The prevalence of depressive symptoms between these two groups was statistically different. This study underlines a strong association between subclinical hypothyroidism and depressive symptoms, which could have some important diagnostic and therapeutic implications in the clinical practice.

  9. Differential Hippocampal Gene Expression and Pathway Analysis in an Etiology-Based Mouse Model of Major Depressive Disorder

    PubMed Central

    Zubenko, George S.; Hughes, Hugh B.; Jordan, Rick M.; Lyons-Weiler, James; Cohen, Bruce M.

    2015-01-01

    We have recently reported the creation and initial characterization of an etiology-based recombinant mouse model of a severe and inherited form of Major Depressive Disorder (MDD). This was achieved by replacing the corresponding mouse DNA sequence witha6-base DNA sequence from the human CREB1promoterthat is associated with MDD in individuals from families with recurrent, early-onset MDD (RE-MDD). In the current study, we explored the effect of the pathogenic Creb1 allele on gene expression in the mouse hippocampus, a brain region that is altered in structure and function in MDD. Mouse whole-genome profiling was performed using the Illumina MouseWG-6 v2.0 Expression BeadChip microarray. Univariate analysis identified 269 differentially-expressed genes in the hippocampus of the mutant mouse. Pathway analyses highlighted 11 KEGG pathways: the phosphatidylinositol signaling system, which has been widely implicated in MDD, Bipolar Disorder, and the action of mood stabilizers; gap junction and long-term potentiation, which mediate cognition and memory functions often impaired in MDD; cardiac muscle contraction, insulin signaling pathway, and three neurodegenerative brain disorders (Alzheimer’s, Parkinson’s, and Huntington’s Diseases) that are associated with MDD; ribosome and proteasome pathways affecting protein synthesis/degradation; and the oxidative phosphorylation pathway that is key to energy production. These findings illustrate the merit of this congenic C57BL/6 recombinant mouse as a model of RE-MDD, and demonstrate its potential for highlighting molecular and cellular pathways that contribute to the biology of MDD. The results also inform our understanding of the mechanisms that underlie the comorbidity of MDD with other disorders. PMID:25059218

  10. Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder.

    PubMed

    Jaso, Brittany A; Niciu, Mark J; Iadarola, Nicolas D; Lally, Niall; Richards, Erica M; Park, Minkyung; Ballard, Elizabeth D; Nugent, Allison C; Machado-Vieira, Rodrigo; Zarate, Carlos A

    2017-01-01

    Current pharmacotherapies for major depressive disorder (MDD) have a distinct lag of onset that can prolong distress and impairment for patients, and realworld effectiveness trials further suggest that antidepressant efficacy is limited in many patients. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms, e.g., receptor/reuptake agonists or antagonists with varying affinities for serotonin, norepinephrine, or dopamine. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, as well as in the development of novel therapeutics for this disorder. Since the rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000, other NMDA receptor antagonists have been studied in MDD. These have been associated with relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics with increased potential in clinical practice (for instance, oral administration, decreased dissociative and/or psychotomimetic effects, and reduced abuse/diversion liability). This article reviews the clinical evidence supporting the use of glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (NR2B)-specific NMDA receptor antagonists (CP- 101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (D-cycloserine, GLYX- 13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). Several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy, but that have yet to be studied clinically, are also briefly discussed; these include α-amino-3-hydroxyl-5-methyl-4- isoxazoleproprionic acid (AMPA) agonists, mGluR2/3 negative

  11. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features.

    PubMed

    Lessel, Davor; Vaz, Bruno; Halder, Swagata; Lockhart, Paul J; Marinovic-Terzic, Ivana; Lopez-Mosqueda, Jaime; Philipp, Melanie; Sim, Joe C H; Smith, Katherine R; Oehler, Judith; Cabrera, Elisa; Freire, Raimundo; Pope, Kate; Nahid, Amsha; Norris, Fiona; Leventer, Richard J; Delatycki, Martin B; Barbi, Gotthold; von Ameln, Simon; Högel, Josef; Degoricija, Marina; Fertig, Regina; Burkhalter, Martin D; Hofmann, Kay; Thiele, Holger; Altmüller, Janine; Nürnberg, Gudrun; Nürnberg, Peter; Bahlo, Melanie; Martin, George M; Aalfs, Cora M; Oshima, Junko; Terzic, Janos; Amor, David J; Dikic, Ivan; Ramadan, Kristijan; Kubisch, Christian

    2014-11-01

    Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma.

  12. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    PubMed Central

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  13. A comparative study of the clinical efficacy and safety of agomelatine with escitalopram in major depressive disorder patients: A randomized, parallel-group, phase IV study

    PubMed Central

    Urade, Chetan S.; Mahakalkar, Sunil M.; Tiple, Prashant G.

    2015-01-01

    Objective: To compare the efficacy of agomelatine with escitalopram in the treatment of major depressive disorder (MDD), improve sleep in MDD patients and study the adverse effects of agomelatine. Materials and Methods: Randomized, parallel-group, open-label study. The primary efficacy outcome was change from baseline to last post-baseline value in Hamilton depression rating scale and Leeds sleep evaluation questionnaire scale. Both parametric and nonparametric tests were applied for analysis. Results: Within-group and between-groups comparison of the mean HAMD17 scores showed statistically significant changes (P < 0.0001). Escitalopram showed early onset of response and remission compared to agomelatine at 10th week (P < 0.0001) and 14th week (P < 0.0001), respectively. In agomelatine, within-group and between-groups change of the mean LSEQ score was statistically significant at subsequent follow-up visits (P < 0.0001). Conclusion: Escitalopram is superior to agomelatine in efficacy, considering the early response, early remission, and better relief from symptoms of MDD in adults. Agomelatine may be preferred in MDD patients having insomnia as a predominant symptom. Liver function monitoring should be done in patients on long-term agomelatine therapy. PMID:26813706

  14. Using Imagery Rescripting to Treat Major Depression: Theory and Practice

    ERIC Educational Resources Information Center

    Wheatley, Jon; Hackmann, Ann

    2011-01-01

    This paper considers the role that intrusive memories may play in maintaining depression and the rationale for using imagery rescripting in order to target these memories. Potential mechanisms of change underlying imagery rescripting are discussed. The relationship between depressive rumination and memories is considered, as well as potential…

  15. Adolescents with Major Depression Demonstrate Increased Amygdala Activation

    ERIC Educational Resources Information Center

    Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido K.; Max, Jeffrey E.; Bischoff-Grethe, Amanda; Lansing, Amy E.; Brown, Gregory; Strigo, Irina A.; Wu, Jing; Paulus, Martin P.

    2010-01-01

    Objective: Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have…

  16. Differential gene expression in patients with subsyndromal symptomatic depression and major depressive disorder

    PubMed Central

    Li, Zezhi; Wang, Qingzhong; Wang, Xuemei; Yuan, Chengmei; Wang, Zuowei; Hong, Wu; Lu, Weihong; Cao, Lan; Chen, Jun; Wang, Yong; Yu, Shunying; Zhou, Yimin; Yi, Zhenghui; Fang, Yiru

    2017-01-01

    Background Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures. Based on these findings, we further clarify whether these genes mRNA was different expressed in peripheral blood in patients with SSD, MDD and healthy controls (60 subjects respectively) Method With the help of the quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), we gained gene relative expression levels among the three groups. Results We found that there are three of the forty eight co-regulated genes had differential expression in peripheral blood among the three groups, which are CD84, STRN, CTNS gene (F = 3.528, p = 0.034; F = 3.382, p = 0.039; F = 3.801, p = 0.026, respectively) while there were no significant differences for other genes. Conclusion CD84, STRN, CTNS gene may have significant value for performing diagnostic functions and classifying SSD, MDD and healthy controls. PMID:28333931

  17. Early-onset sensorineural hearing loss in Lassa fever.

    PubMed

    Ibekwe, T S; Okokhere, P O; Asogun, D; Blackie, F F; Nwegbu, M M; Wahab, K W; Omilabu, S A; Akpede, G O

    2011-02-01

    Lassa fever (LF) is a viral hemorrhagic disease which affects one-fourth to two million people annually with the fatality rate of about 10,000. It is associated with sensorineural hearing loss (SNHL) usually at the convalescent stage. Recently, cases of SNHL at the acute phase have been reported. This study was done to further investigate the incidence and features of SNHL in acute phase of LF. It is a prospective case-control study of LF patients seen with acute SNHL conducted between July 2007 and April 2009 at Irrua Specialist Teaching Hospital Nigeria. The diagnosis of acute LF was based on the clinical features and detection of IgM antibodies and/or positive Lassa virus-specific reverse transcriptase-polymerase chain reaction using primers S36+ and LVS 339 while SNHL was diagnosed clinically and confirmed with PTA and speech discrimination tests. Patients with other acute febrile illnesses were used as control. Statistical analysis was done using SPSS version 11 and Fisher's exact test while level of significance was set at p < 0.05. Out of the 37 confirmed cases of LF, 5 (13.5%) and none (0%) of the control developed early-onset SNHL (p = 0.03). Forty percent of the cases studied had negative IgM. The audiograms showed involvement at all frequency groups with pure tone average 65-85 dB and the speech discrimination 20-40%. The overall case fatality rate was 27.0%, and for early SNHL cases 60.0% (p > 0.05). The incidence of SNHL in LF infection is about 13.5% and could be a reflection of a worse disease process. There is possibility of direct viral invasion aside immunological reaction as a causative mechanism.

  18. Early onset of ghrelin production in a marsupial.

    PubMed

    Menzies, Brandon R; Shaw, Geoff; Fletcher, Terry P; Renfree, Marilyn B

    2009-02-27

    Ghrelin regulates appetite in mammals and can stimulate growth hormone (GH) release from the pituitary. In rats and humans, ghrelin cells appear in the stomach during late fetal life. Nevertheless, the role of ghrelin in early mammalian development is not well understood. Marsupials deliver highly altricial young that weigh less than 1g so they must feed and digest milk at a comparatively immature stage of development. Since they complete their growth and differentiation while in the pouch, they are accessible models in which to determine the time course of ghrelin production during development. We examined the distribution of gastric ghrelin cells, plasma ghrelin concentrations and pituitary expression of the ghrelin receptor (ghsr-1alpha) and GH in the tammar wallaby, Macropus eugenii. There were ghrelin immunopositive cells in the developing mesenchyme of the stomach from day 10 post partum (pp) to day 150pp. Subsequently ghrelin protein in the fore-stomach declined and was absent by day 250pp but remained in the gastric cells of the hind-stomach. Ghrelin was detected in the developing pancreas from day 10pp but was absent by day 150pp and in the adult. Pituitary ghsr-1alpha expression and plasma concentrations of ghrelin increased significantly up to day 70-120pp while GH expression was also elevated, declining with GH to reach adult levels by day 180pp. These results demonstrate an early onset of gastric ghrelin expression in the tammar in concert with a functional stomach at a relatively earlier stage than that of developmentally more mature eutherian young.

  19. Child and Adolescent (Early Onset) Schizophrenia: A Review in Light of DSM-III-R.

    ERIC Educational Resources Information Center

    Werry, John S.

    1992-01-01

    This review of studies of early onset schizophrenia examines the nosological similarity between adult and early onset schizophrenia, differential diagnosis, treatment, and the extent to which children and adolescents diagnosed as having schizophrenia using adult criteria have the characteristic adult correlates. The paper discusses gender…

  20. 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…

  1. Children with Very Early Onset Obsessive-Compulsive Disorder: Clinical Features and Treatment Outcome

    ERIC Educational Resources Information Center

    Nakatani, Eriko; Krebs, Georgina; Micali, Nadia; Turner, Cynthia; Heyman, Isobel; Mataix-Cols, David

    2011-01-01

    Background: There is emerging evidence that early onset obsessive-compulsive disorder (OCD) may be a phenomenologically distinct subtype of the disorder. Previous research has shown that individuals who report an early onset display greater severity and persistence of symptoms, and they may be less responsive to treatment. To date, this question…

  2. Family Functioning and Early Onset of Sexual Intercourse in Latino Adolescents

    ERIC Educational Resources Information Center

    Velez-Pastrana, Maria C.; Gonzalez-Rodriguez, Rafael A.; Borges-Hernandez, Adalisse

    2005-01-01

    The purpose of this study was to identify factors associated with early onset of sexual intercourse. Within an ecological system's conceptual framework, familial factors associated with early onset of sexual activity were identified in a sample of 425 adolescents from San Juan metro area schools. Measures included questions about sexual activity,…

  3. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  4. Self-reported inability to cry as a symptom of anhedonic depression in outpatients with a major depressive disorder.

    PubMed

    Steer, Robert A

    2011-06-01

    To ascertain whether self-reported inability to cry would be associated with symptoms of anhedonic depression, the 21-item Beck Depression Inventory-II was administered to 1,050 outpatients diagnosed with a DSM-IV-TR major depressive disorder. 219 (21%) patients reported on the BDI-II Crying item that they were unable to cry, and 831 (79%) patients reported they were able to cry. Only BDI-II Loss of Interest was significantly associated with the inability to cry after the other BDI-II symptoms were controlled for using a multiple logistic-regression analysis. The inability to cry was discussed as an indicator of anhedonic depression.

  5. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.

  6. Association between toll-like receptors expression and major depressive disorder.

    PubMed

    Hung, Yi-Yung; Kang, Hong-Yo; Huang, Kai-Wei; Huang, Tiao-Lai

    2014-12-15

    Accumulating evidences suggest that Toll-like receptors (TLRs) were involved in the pathophysiology of major depressive disorder. TLR4 was thought to be associated with major depressive disorder in animal model, but the others were still unknown. In order to examine TLR1-9 mRNA expression levels in peripheral blood and their relationships with the psychopathology of major depressive disorder, 30 patients with major depressive disorder were compared with 29 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess the severity of major depression. The mRNA expression levels of TLRs were examined in parallel with a housekeeping gene using real-time polymerase chain reaction (RT-PCR). Analysis of covariance with age and body mass index adjustment revealed a significantly higher expression of TLR3, 4, 5 and 7 mRNA but lower expression of TLR1 and 6 in patients with major depressive disorder as compared with healthy controls. Multiple linear regression analysis revealed that TLR4 was an independent risk factor relating to severity of major depression. These findings suggest that TLRs, especially TLR4, may be involved in the psychopathology of major depression.

  7. The association of major depressive episode and personality traits in patients with fibromyalgia

    PubMed Central

    de Melo Santos, Danyella; Lage, Laís Verderame; Jabur, Eleonora Kehl; Kaziyama, Helena Hideko Seguchi; Iosifescu, Dan V; de Lucia, Mara Cristina Souza; Fráguas, Renério

    2011-01-01

    INTRODUCTION: Personality traits have been associated with primary depression. However, it is not known whether this association takes place in the case of depression comorbid with fibromyalgia. OBJECTIVE: The authors investigated the association between a current major depressive episode and temperament traits (e.g., harm avoidance). METHOD: A sample of 69 adult female patients with fibromyalgia was assessed with the Temperament and Character Inventory. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview severity of depressive symptomatology with the Beck Depression Inventory, and anxiety symptomatology with the IDATE-state and pain intensity with a visual analog scale. RESULTS: A current major depressive episode was diagnosed in 28 (40.5%) of the patients. They presented higher levels of harm avoidance and lower levels of cooperativeness and self-directedness compared with non-depressed patients, which is consistent with the Temperament and Character Inventory profile of subjects with primary depression. However, in contrast to previous results in primary depression, no association between a major depressive episode and self-transcendence was found. CONCLUSIONS: The results highlight specific features of depression in fibromyalgia subjects and may prove important for enhancing the diagnosis and prognosis of depression in fibromyalgia patients. PMID:21808861

  8. Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications.

    PubMed

    Kudlow, P; Cha, D S; Carvalho, A F; McIntyre, R S

    2016-01-01

    Major depressive disorder (MDD) is a multi-factorial and heterogeneous disease. Robust evidence suggests that inflammation is involved in the pathogenesis of MDD for a subpopulation of individuals. However, it remains unclear what traits and/or states precede the onset of inflammation in this subpopulation of individuals with MDD. Several recent studies have implicated nitric oxide (NO) as a critical regulator of neuroinflammation, thus suggesting a possible role in the pathophysiology of MDD. The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for developing MDD in certain subpopulations may be mediated, in part, by inflammogenic trait and/or state variations in NO signaling pathways. We conducted a non-systematic literature search for English language studies via PubMed and Google Scholar, from 1985 to October 2014. Replicated evidence suggests that NO has contrasting effects in the central nervous system (CNS). Low concentrations of NO are neuroprotective and mediate physiological signaling whereas higher concentrations mediate neuroinflammatory actions and are neurotoxic. Certain polymorphisms in the neuronal nitric oxide synthase gene (NOS1) are associated MDD. Furthermore, state variations (e.g. decreased levels of essential co-factor, 5,6,7,8-tetrahydrobiopterin [BH4], enhanced microglial cell activity) in the NO signaling pathway are associated with an increased risk of developing MDD. Increased concentrations of NO enhance the production of reactive nitrogen species (RNS) and reactive oxygen species (ROS), which are associated with an increase in pro-inflammatory cytokines. Taken together, evidences suggest that abnormalities in NO signaling may constitute a trait-marker related to MDD pathophysiology, which could be explored for novel therapeutic targets.

  9. Salience Network Functional Connectivity Predicts Placebo Effects in Major Depression

    PubMed Central

    Sikora, Magdalena; Heffernan, Joseph; Avery, Erich T.; Mickey, Brian J.; Zubieta, Jon-Kar; Peciña, Marta

    2015-01-01

    Background Recent neuroimaging studies have demonstrated resting-state functional connectivity (rsFC) abnormalities among intrinsic brain networks in Major Depressive Disorder (MDD); however, their role as predictors of treatment response has not yet been explored. Here, we investigate whether network-based rsFC predicts antidepressant and placebo effects in MDD. Methods We performed a randomized controlled trial of two weeklong, identical placebos (described as having either “active” fast-acting, antidepressant effects or as “inactive”) followed by a ten-week open-label antidepressant medication treatment. Twenty-nine participants underwent a rsFC fMRI scan at the completion of each placebo condition. Networks were isolated from resting-state blood-oxygen-level-dependent signal fluctuations using independent component analysis. Baseline and placebo-induced changes in rsFC within the default-mode, salience, and executive networks were examined for associations with placebo and antidepressant treatment response. Results Increased baseline rsFC in the rostral anterior cingulate (rACC) within the salience network, a region classically implicated in the formation of placebo analgesia and the prediction of treatment response in MDD, was associated with greater response to one week of active placebo and ten weeks of antidepressant treatment. Machine learning further demonstrated that increased salience network rsFC, mainly within the rACC, significantly predicts individual responses to placebo administration. Conclusions These data demonstrate that baseline rsFC within the salience network is linked to clinical placebo responses. This information could be employed to identify patients who would benefit from lower doses of antidepressant medication or non-pharmacological approaches, or to develop biomarkers of placebo effects in clinical trials. PMID:26709390

  10. Dietary patterns and anthropometric indices among Iranian women with major depressive disorder.

    PubMed

    Rashidkhani, Bahram; Pourghassem Gargari, Bahram; Ranjbar, Fatemeh; Zareiy, Sanaz; Kargarnovin, Zahra

    2013-11-30

    Major depression is a common mental disorder among women. A number of studies have demonstrated the association between some nutrients and food items with depression, but the studies on the association of dietary patterns with depression, especially in the Middle East, are rare. Further, the literature examining the relationship between anthropometric status and depression are inconsistent. In this study, 45 women with major depression and 90 patients with no mental disorder participated. We collected dietary intakes by a semi-quantitative food frequency questionnaire, and measured anthropometric indices (weight, height, waist and hip circumferences). Using factor analysis, two major dietary patterns were extracted: Healthy and Unhealthy. After adjusting for confounders, individuals who gained higher scores in healthy dietary pattern, had 84% lower odds of major depression; while the odds of major depression in participants who gained higher scores in unhealthy dietary pattern showed no significant association. No significant association was found between anthropometric indices and major depression. These results suggest that the healthy dietary pattern is significantly associated with lower odds of major depression in adult women. Further researches are needed to confirm these findings.

  11. Epidemiology of early-onset dementia: a review of the literature

    PubMed Central

    Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

    2013-01-01

    Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

  12. Current perspectives on the diagnosis and treatment of major depressive disorder.

    PubMed

    Nierenberg, A A

    2001-09-01

    Each year in America approximately 6 million people suffer from depression at a cost of more than $16 billion. People who are depressed have more medical illnesses than those without depression and make greater use of healthcare services. In a 15-month period after having been diagnosed with depression, sufferers are 4 times more likely to die as those who do not have depression. Almost 60% of suicides have their roots in major depression, and 15% of those admitted to a psychiatric hospital for depression eventually kill themselves. Although depression is highly treatable, only one third of sufferers receive suitable treatment. The reason for underdiagnosis is 2-fold. Physicians may fail to recognize depression and sufferers may actively deny it. A family history of depression is an important cause in those who suffer recurrent episodes. Major depressive disorder is the most common type of depression and, unless treated, resolves by itself in 6 months to a year less than 40% of the time. Depressive symptoms can be found in as many as 30% of those who abuse alcohol, so abstinence is crucial to treatment. Contrary to popular belief, depression is not a normal part of aging, although it can occur in elderly people who have severe medical and psychosocial problems. The goal of pharmacotherapy is the reduction and ultimate removal of all signs and symptoms of depression. More than 2 dozen drugs with 7 distinct mechanisms of action are available to treat depression, with the clinical goal being remission. Whereas psychotherapy is a treatment option, by itself it tends to be effective in only a limited group of highly motivated individuals who have less severe forms of depression. As a result, treatment outcomes are better when pharmacologic antidepressant treatment and psychotherapy are combined.

  13. The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson's Disease.

    PubMed

    D'Ostilio, Kevin; Garraux, Gaëtan

    2016-01-01

    The high prevalence of major depressive disorder in people with Parkinson's disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions.

  14. A test of the tripartite model's prediction of anhedonia's specificity to depression: patients with major depression versus patients with schizophrenia.

    PubMed

    Joiner, Thomas E; Brown, Jessica S; Metalsky, Gerald I

    2003-08-01

    The tripartite model of depression and anxiety suggests that anhedonia represents a relatively specific marker of depression. A strong version of this view is that anhedonic symptoms would particularly characterize depressed patients, even when compared to another diagnostic group-schizophrenic patients-for whom anhedonic symptoms represent a well-studied feature. This prediction was tested among 102 VA psychiatric inpatients (95 men), ages 21-72 (M=43.56; S.D.=8.47), all of whom received diagnoses of either major depression (n=50) or schizophrenia (n=52) based on structured diagnostic interviews. As predicted, patients with major depression scored significantly higher on the anhedonic symptoms scale of the Beck Depression Inventory (BDI) than did patients with schizophrenia. However, there was no difference between the two groups on the BDI total score or the BDI non-anhedonic symptoms score. Consistent with the tripartite model, anhedonic symptoms were more related to depressive vs. schizophrenic diagnostic status, whereas non-anhedonic depressive symptoms were not. Within the study's limitations, results were interpreted as relatively strong support for the validity and extension of the tripartite model.

  15. Major Depressive Disorder in Military Aviators: A Retrospective Study of Prevalence

    DTIC Science & Technology

    2008-08-01

    decrease in libido, appetite changes, and suicidal ideation (8). To be diagnosed with major depression, one must experience the majority of these...depression such as difficulty concentrating, decreased energy, feelings of helplessness and/or hopelessness, sleep disturbance, or suicidal ideation profoundly

  16. A Pilot Study of Adjunctive Family Psychoeducation in Adolescent Major Depression: Feasibility and Treatment Effect

    ERIC Educational Resources Information Center

    Sanford, Mark; Boyle, Michael; McCleary, Lynn; Miller, Jennifer; Steele, Margaret; Duku, Eric; Offord, David

    2006-01-01

    Objective: To obtain preliminary evidence of the feasibility and effectiveness of adjunctive family psychoeducation in adolescent major depressive disorder. Method: Participants were from outpatient clinics in Hamilton and London, Ontario. Over 24 months, 41 adolescents ages 13 through 18 years meeting major depressive disorder criteria were…

  17. A Pilot Study of Culturally Adapted Cognitive Behavior Therapy for Hispanics with Major Depression

    ERIC Educational Resources Information Center

    Interian, Alejandro; Allen, Lesley A.; Gara, Michael A.; Escobar, Javier I.

    2008-01-01

    The purpose of this study was to evaluate a culturally adapted cognitive-behavioral treatment (CBT) for major depression among Hispanics in primary care. Cultural adaptations were applied based on a range of cultural considerations described in the literature. Fifteen Hispanic primary care patients with major depression were enrolled. All…

  18. Selected Executive Skills in Adolescents with Recent First Episode Major Depression

    ERIC Educational Resources Information Center

    Kyte, Zoe A.; Goodyer, Ian M.; Sahakian, Barbara J.

    2005-01-01

    Background: To investigate whether recent first episode major depression in adolescence is characterised by selected executive difficulties in attentional flexibility, behavioural inhibition and decision-making. Methods: Selected executive functions were compared in adolescents with recent (past year) first episode major depression (n = 30) and…

  19. Racial/Ethnic Differences in Mental Health Service Use among Adolescents with Major Depression

    ERIC Educational Resources Information Center

    Cummings, Janet R.; Druss, Benjamin G.

    2011-01-01

    Objective: Little is known about racial/ethnic differences in the receipt of treatment for major depression in adolescents. This study examined differences in mental health service use in non-Hispanic white, black, Hispanic, and Asian adolescents who experienced an episode of major depression. Method: Five years of data (2004-2008) were pooled…

  20. Evidence against mood-congruent attentional bias in Major Depressive Disorder.

    PubMed

    Cheng, Philip; Preston, Stephanie D; Jonides, John; Mohr, Alicia Hofelich; Thummala, Kirti; Casement, Melynda; Hsing, Courtney; Deldin, Patricia J

    2015-12-15

    Depression is consistently associated with biased retrieval and interpretation of affective stimuli, but evidence for depressive bias in earlier cognitive processing, such as attention, is mixed. In five separate experiments, individuals with depression (three experiments with clinically diagnosed major depression, two experiments with dysphoria measured via the Beck Depression Inventory) completed three tasks designed to elicit depressive biases in attention, including selective attention, attentional switching, and attentional inhibition. Selective attention was measured using a modified emotional Stroop task, while attentional switching and inhibition was examined via an emotional task-switching paradigm and an emotional counter task. Results across five different experiments indicate that individuals with depression perform comparably with healthy controls, providing corroboration that depression is not characterized by biases in attentional processes.

  1. Imaging Phenotypes of Major Depressive Disorder: Genetic Correlates

    PubMed Central

    Savitz, Jonathan B; Drevets, Wayne C

    2009-01-01

    Imaging techniques are a potentially powerful method of identifying phenotypes that are associated with, or are indicative of a vulnerability to developing major depressive disorder (MDD). Here we identify seven promising MDD-associated traits identified by magnetic resonance imaging (MRI) or positron emission tomography (PET). We evaluate whether these traits are state-independent, heritable endophenotypes, or state-dependent phenotypes that may be useful markers of treatment efficacy. In MDD, increased activity of the amygdala in response to negative stimuli appears to be a mood-congruent phenomenon, and is likely moderated by the serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR). Hippocampal volume loss is characteristic of elderly or chronically-ill samples and may be impacted by the val66met brain-derived neurotrophic factor (BDNF) gene variant and the 5-HTTLPR SLC6A4 polymorphism. White matter pathology is salient in elderly MDD cohorts but is associated with cerebrovascular disease, and is unlikely to be a useful marker of a latent MDD diathesis. Increased blood flow or metabolism of the subgenual anterior cingulate cortex (sgACC), together with gray matter volume loss in this region, is a well-replicated finding in MDD. An attenuation of the usual pattern of fronto-limbic connectivity, particularly a decreased temporal correlation in amygdala-anterior cingulate cortex (ACC) activity, is another MDD-associated trait. Concerning neuroreceptor PET imaging, decreased 5-HT1A binding potential in the raphe, medial temporal lobe, and medial prefrontal cortex (mPFC) has been strongly associated with MDD, and may be impacted by a functional single nucleotide polymorphism in the promoter region of the 5-HT1A gene (HTR1A: –1019C/G; rs6295). Potentially indicative of inter-study variation in MDD etiology or mood state, both increased and decreased binding potential of the serotonin transporter has been reported. Challenges facing the field include

  2. Personalized medicine in major depressive disorder -- opportunities and pitfalls.

    PubMed

    Miller, Diane B; O'Callaghan, James P

    2013-01-01

    The sequencing of the human genome in the early days of this millennium was greeted with great fanfare as this accomplishment was expected to revolutionize medicine and result in individualized treatments based on the genetic make-up of the patient. The ultimate promise of personalized medicine would be fulfilled with the identification of disease biomarkers that would be widely available for use in diagnosis and treatment. Progress, however, has been slow in providing disease biomarkers or approved diagnostic tests. This is true for major depressive disorder (MDD), despite its prevalence in the general population and the widespread acceptance of its biological basis. Studies using strategies like genome-wide association and candidate gene analyses have identified a number of possible biomarkers of MDD, including serum levels of neurotrophic factors, inflammatory cytokines and HPA axis hormones, but none have proven sufficiently powerful for clinical use. The lack of biologically based tests available for use in identifying patients with MDD is a significant impediment to personalized and more effective treatment, because it means diagnosis continues to be driven by subjective symptoms. While genetic studies of MDD have not yet led to diagnostic and treatment biomarkers, progress in determining the role of the genome in drug metabolism heralds the first effort in personalized prescribing for the antidepressants. The FDA suggested and approved genotyping tests for common variants of drug metabolism genes, such as the cytochrome p450s. By using these tests a physician can select an appropriate antidepressant for a given patient, as differences in clearance, half-life, and peak blood concentrations are controlled by genetic variability in drug metabolism. Personalization in drug choice can be achieved because these tests: (1) identify responders and non-responders; (2) provide alerts to possible adverse drug events; and (3) help optimize dose. Improved ways of

  3. Cognitive functioning and cortisol profiles in first episode major depression.

    PubMed

    Hansson, Pia Berner; Murison, Robert; Lund, Anders; Hammar, Åsa

    2015-08-01

    Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies have shown a relationship between cortisol profile and cognitive functioning in recurrent MDD in general. More specifically, the association between hypercortisolism and cognitive functioning, such as memory and Executive Functioning (EF), and also more recently cortisol suppression has been explored. However, no studies have investigated these relationships in patients diagnosed with first episode MDD. The aim of the present study was to examine the relationship between cortisol levels before and after the Dexamethasone suppression test (DST) and cognitive function in first episode MDD patients. Twenty-one patients meeting the DSM-IV criteria for a first episode of MDD diagnosis were included in the study. The control group was matched for age, gender and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given orally on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring executive functioning (EF) and memory functioning. Cortisol levels did not differ significantly between patients and controls on Day 1, except for the last sample before Dexamethasone administration, where the control group showed higher levels. Both groups showed suppression after Dexamethasone. On Day 2 there was a significant difference between groups at the third sample, showing a significantly lower level in the control group, suggesting that the controls have a more effective suppression profile than the patients. There were no significant correlations between cortisol levels before or after

  4. Eating Disorders and Major Depression: Role of Anger and Personality

    PubMed Central

    Giovanni, Abbate-Daga; Carla, Gramaglia; Enrica, Marzola; Federico, Amianto; Maria, Zuccolin; Secondo, Fassino

    2011-01-01

    This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self-Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD. PMID:21977317

  5. Association study of the dopamine transporter gene with personality traits and major depressive disorder in the Han Chinese population.

    PubMed

    Huang, Chang-Chih; Lu, Ru-Band; Shih, Mei-Chen; Yen, Che-Hung; Huang, San-Yuan

    2011-02-01

    Major depression is a complex psychiatric disorder involving multiple factors, including genetic and personality components. This study used 17 polymorphisms of dopamine transporter gene (DAT1) to explore whether this gene is associated with major depression and whether it influences personality traits in patients with major depression. The DAT1 polymorphisms were analyzed in 1017 unrelated individuals and 459 patients were eligible to assess personality traits. We found a borderline association between controls and total major depression and between major depression with family history versus controls; however, these differences were obscured after correction for multiple testing. Furthermore, the DAT1 polymorphisms were not associated either with major depression in haplotype analysis or with personality traits. Despite the fact that several association tendencies were found between DAT1 and major depression, we did not confirm a major role for DAT1 in the susceptibility to major depression. In addition, DAT1 does not seem to affect personality traits observed in patients with major depression.

  6. Phonologically-Based Biomarkers for Major Depressive Disorder

    DTIC Science & Technology

    2011-04-26

    COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...measures of depression severity and treatment response collected via interactive voice response (IVR) technology." Journal of Neurolinguistics 20(1

  7. Psychological vulnerabilities in patients with major depression vs panic disorder.

    PubMed

    Cox, B J; Enns, M W; Walker, J R; Kjernisted, K; Pidlubny, S R

    2001-05-01

    The tripartite model (Clark & Watson, 1991: Clark, L. A., & Watson, D. (1991). Tripartite model of anxiety and depression: Psychometric evidence and taxonomic implications. Journal of Abnormal Psychology, 100, 316-336) posits that anxiety and depression share nonspecific features of neuroticism but that somatic arousal appears unique to anxiety, and low positive affect appears unique to depression. The present study controlled for these higher-order effects and evaluated the relative contributions of four, specific lower-order vulnerabilities (anxiety sensitivity, rumination, self-criticism, self-oriented perfectionism). Participants were 38 depressed patients and 38 patients with panic disorder matched as closely as possible for age and gender, and all were diagnosed using the same structured interview by an experienced clinician. Results from hierarchical logistic regression analysis were consistent with predictions from the tripartite model in that only the unique features of arousal and positive affectivity differentiated the two diagnostic groups. At a lower-order level, only anxiety sensitivity (and its facet of fear of physical symptoms) and a ruminative response style demonstrated incremental predictive ability. The discussion focuses on the relationships among these higher-order and lower-order variables, and their potential importance for understanding specific manifestations of psychopathology.

  8. Major depression in 1998: are we providing optimal therapy?

    PubMed

    Angst, J

    1999-01-01

    Depression is a common illness associated with long duration of episodes, high rates of chronicity, relapse and recurrence, psychosocial and physical impairment, and high suicide rate. A lifetime prevalence of approximately 17% has been widely reported, and the likelihood of recurrence is more than 50%. A conceptual shift has occurred in our understanding of depression. It is now seen as a chronic medical disorder that produces as much functional limitation and morbidity as chronic diseases such as hypertension and diabetes. Predictors of chronicity include long duration of index episode, relationship difficulties, low family income, admitting research center, and inpatient hospitalization. Risk factors for recurrence include lack of self-confidence, neuroticism, previous hospital admission, loss events, and age. The aim of treatment is to induce a stable, fully asymptomatic state with full restoration of psychosocial function and to establish a long-term state of wellness. Despite effective pharmacotherapy, depressed patients are often underdiagnosed and undertreated by both psychiatrists and primary care physicians. The psychosocial and physical impairment, comorbidity, and high suicide rate associated with chronic, recurrent depression require optimal treatment strategies. The future of antidepressant treatment should focus on remission or getting the patient well and drugs that will induce and maintain long-term recovery.

  9. The Role of Neurotrophins in Major Depressive Disorder.

    PubMed

    Jiang, Cheng; Salton, Stephen R

    2013-03-01

    Neurotrophins and other growth factors have been advanced as critical modulators of depressive behavior. Support for this model is based on analyses of knockout and transgenic mouse models, human genetic studies, and screens for gene products that are regulated by depressive behavior and/or antidepressants. Even subtle alteration in the regulated secretion of brain-derived neurotrophic factor (BDNF), for example, due to a single nucleotide polymorphism (SNP)-encoded Val-Met substitution in proBDNF that affects processing and sorting, impacts behavior and cognition. Alterations in growth factor expression result in changes in neurogenesis as well as structural changes in neuronal cytoarchitecture, including effects on dendritic length and spine density, in the hippocampus, nucleus accumbens, and prefrontal cortex. These changes have the potential to impact the plasticity and stability of synapses in the CNS, and the complex brain circuitry that regulates behavior. Here we review the role that neurotrophins play in the modulation of depressive behavior, and the downstream signaling targets they regulate that potentially mediate these behavioral pro-depressant and antidepressant effects.

  10. Objective Sleep in Pediatric Anxiety Disorders and Major Depressive Disorder

    ERIC Educational Resources Information Center

    Forbes, Erika E.; Bertocci, Michele A.; Gregory, Alice M.; Ryan, Neal D.; Axelson, David A.; Birmaher, Boris; Dahl, Ronald E.

    2008-01-01

    A study to examine sleep problems encountered in anxiety and depressive disorders among children and adolescents is conducted. Results indicated subjective and objective sleep problems in children and adolescents with anxiety disorders and need to be kept in mind when treating young anxious people.

  11. Personality, Stressful Life Events, and Treatment Response in Major Depression

    ERIC Educational Resources Information Center

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  12. Difference in amplitude of low-frequency fluctuation between currently depressed and remitted females with major depressive disorder.

    PubMed

    Jing, Bin; Liu, Chun-Hong; Ma, Xin; Yan, Hua-Gang; Zhuo, Zhi-Zheng; Zhang, Yu; Wang, Su-Hong; Li, Hai-Yun; Wang, Chuan-Yue

    2013-12-02

    Medical intervention for major depressive disorder (MDD) can be more appropriately focused through the identification and characterization of neurobiological markers that are specific to the disorder, and this study aims to examine the abnormality in the fractional amplitude of low-frequency fluctuation (fALFF) and the amplitude of low-frequency fluctuation (ALFF) in currently depressed and remitted female MDD patients and to correlate these fluctuations with clinical markers of MDD. Nineteen currently depressed female patients, 19 remitted female patients, as well as 19 age- and education-matched healthy females participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the fALFF/ALFF maps among the three groups and investigated the correlation between clinical measurements and statistically significant differences in the fALFF/ALFF of various brain regions. Compared with healthy controls, both currently depressed and remitted patients showed increased fALFF/ALFF in the right putamen. Currently depressed MDD patients showed increased fALFF/ALFF in the right ventral median frontal gyrus relative to both the remitted MDD group and the healthy control group. The ALFF of the right precuneus was found to be positively correlated with the number of depressive episodes and the fALFF of the right precuneus to be positively correlated with the disease duration in currently depressed MDD patients. An abnormal fALFF/ALFF in the right ventral median frontal gyrus was found only in currently depressed patients, suggesting that such an anomaly may play a critical role in depressive symptomatology and may be a therapeutic target for MDD. An abnormal fALFF/ALFF in the right putamen is a potential candidate as a trait-related marker of vulnerability to major depression.

  13. Narrative therapy for adults with major depressive disorder: improved symptom and interpersonal outcomes.

    PubMed

    Vromans, Lynette P; Schweitzer, Robert D

    2011-01-01

    This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder.

  14. Major depression: the relative contribution of gender, MDMA, and cannabis use.

    PubMed

    Durdle, Heather; Lundahl, Leslie H; Johanson, Chris-Ellyn; Tancer, Manuel

    2008-01-01

    Previous research has suggested that 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) users have elevated depressive symptomatology, although it is not clear whether this is due to MDMA or other drug use. This study aimed to investigate the contributions of MDMA and cannabis use to Major Depressive Disorder in MDMA users. A total of 226 MDMA users were studied. Participants (65% male) reported an average number of 35.8 uses of MDMA (SD = 45.6, range = 2-400). Participants were administered a Structured Clinical Interview for DSM-IV. Twenty-six individuals (11.5%) met lifetime criteria for Major Depressive Disorder. High rates of lifetime Cannabis Abuse (30.1%) and Cannabis Dependence (12.4%) were reported. No association was found between number of uses of MDMA and Major Depressive Disorder. Those with lifetime major depression were found, however, to have higher rates of lifetime cannabis use disorder (adjusted OR = 2.40). A logistic regression indicated that lifetime cannabis use disorder, but not MDMA use, was significantly associated with lifetime Major Depressive Disorder. Stratified analyses suggested that for males, neither drug use variable was associated with major depression. For females, a lifetime cannabis use disorder (adjusted OR = 4.99), but not MDMA use, was associated with lifetime Major Depressive Disorder. Results of this study suggest that although MDMA use was not found to be significantly associated with major depression for either gender, a lifetime cannabis use disorder was significantly associated with lifetime major depression for female, but not male, users of MDMA.

  15. Co-variation of depressive mood and spontaneous physical activity evaluated by ecological momentary assessment in major depressive disorder.

    PubMed

    Kim, Jinhyuk; Nakamura, Toru; Kikuchi, Hiroe; Yoshiuchi, Kazuhiro; Yamamoto, Yoshiharu

    2014-01-01

    The objective evaluation of depressive mood is thought to be useful for the diagnosis and treatment of depressive disorders. Thus, we investigated psychobehavioral correlates, particularly the statistical associations between momentary depressive mood and behavioral dynamics measured objectively, in patients with major depressive disorder (MDD). Patients with MDD (n = 14) wore a watch-type computer device and rated their momentary symptoms using ecological momentary assessment. Spontaneous physical activity in daily life, referred to as locomotor activity, was also continuously measured by an activity monitor built into the device. A multilevel modeling approach was used to model the associations between changes in depressive mood scores and the local statistics of locomotor activity simultaneously measured. The statistical model constructed indicated that worsening of depressive mood was associated with increased intermittency of locomotor activity, as characterized by a lower mean and higher skewness. Our findings suggest the presence of associations between momentary depressive mood and behavioral dynamics in patients with depression, which may lead to the continuous monitoring of the pathological states of MDD.

  16. The Latent Symptom Structure of the Beck Depression Inventory-II in Outpatients with Major Depression

    ERIC Educational Resources Information Center

    Quilty, Lena C.; Zhang, K. Anne; Bagby, R. Michael

    2010-01-01

    The Beck Depression Inventory-II (BDI-II) is a self-report instrument frequently used in clinical and research settings to assess depression severity. Although investigators have examined the factor structure of the BDI-II, a clear consensus on the best fitting model has not yet emerged, resulting in different recommendations regarding how to best…

  17. 2D-DIGE proteome analysis on the platelet proteins of patients with major depression

    PubMed Central

    2014-01-01

    Introduction Platelet activation is related to the psychopathology of major depression. We attempted to search and identify protein biomarkers from the platelets of patients with major depression. High resolution two-dimensional Differential Gel Electrophoresis (2D-DIGE), the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), Western blot, and bioinformatic tools were applied to examine the platelet proteins of 10 patients with major depression and 10 healthy controls. Results The levels of 8 proteins were significantly different between the patients with major depression in the acute phase and healthy controls. The levels of protein disulfide-isomerase A3 (PDIA3) and F-actin-capping protein subunit beta (CAPZB) were higher in patients with major depression than in healthy controls. The levels of fibrinogen beta chain (FIBB), fibrinogen gamma chain (FIBG), retinoic acid receptor beta (RARB), glutathione peroxidase 1 (GPX1), SH3 domain-containing protein 19 (SH319), and T-complex protein 1 subunit beta (TCPB) were lower in patients with major depression than in healthy controls. Conclusions Platelet provided valuable information about the pathways and processes of inflammation/immunity, oxidative stress, and neurogenesis, related to major depression. PMID:24383611

  18. Rate and Predictors of Persistent Major Depressive Disorder in a Nationally Representative Sample.

    PubMed

    Walker, Elizabeth Reisinger; Druss, Benjamin G

    2015-08-01

    This study examined predictors of persistent major depressive disorder over 10 years, focusing on the effects of clinical variables, physical health, and social support. Data from the National Survey of Midlife Development in the United States in 1995-1996 and 2004-2006 were analyzed. Logistic regression was used to predict non-recovery from major depression among individuals who met clinical-based criteria for major depressive disorder at baseline. Fifteen percent of the total sample was classified as having major depression in 1995-1996; of these individuals, 37 % had major depression in 2004-2006. Baseline variables that were significantly associated with persistent major depression at follow-up were being female, having never married, having two or more chronic medical conditions, experiencing activity limitation, and less contact with family. Therefore, treatment strategies focused on physical health, social support, and mental health needs are necessary to comprehensively address the factors that contribute to persistent major depressive disorder.

  19. Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

    PubMed Central

    2014-01-01

    Background Although genetic variation is believed to contribute to an individual’s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder. Results Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Conclusions Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease. PMID:24694013

  20. Frequency of psychological and somatic symptoms in patients with major depressive disorder.

    PubMed

    Chaudhry, Haroon Rashid; Arshad, Nadia; Javed, Faeza; Asif, Aftab

    2010-09-01

    Major depressive disorder (MDD) is one of the most commonly encountered psychiatric disorders in primary care. Depression is primarily a psychological illness; however, patients usually present with somatic symptoms. This pattern of presentation quite often poses a risk for patients with MDD due to the fact that general practitioners commonly attribute the cause of somatic symptoms to organic illnesses, thereby misdiagnosing patients. The current study focuses on the frequency of psychological and somatic symptoms in patients with major depressive disorder. The study is a cross-sectional survey using non-probability purposive sampling technique. The authors administered a self-developed questionnaire on 900 patients (male and female) diagnosed with major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders-IV-TR (DSM-IV-TR). The data was analyzed using Statistical Package for Social Sciences-10 (SPSS-10). Females presented with a higher frequency of somatic symptoms as compared to psychological symptoms, whereas males presented with a higher frequency of psychological symptoms as compared to somatic symptoms. These findings emphasize the imperative need for health care professionals to have a thorough understanding of major depressive disorder. The disabling effects of depression can be minimized and prognosis of such patients improved to the point of remission if depression is promptly diagnosed without ambiguity, and intensively treated based on the physician's comprehensive knowledge of the symptomatology of major depressive disorder.

  1. Early-Onset, Regular Cannabis Use Is Linked to IQ Decline

    MedlinePlus

    ... Is Linked to IQ Decline Early-Onset, Regular Cannabis Use Is Linked to IQ Decline Email Facebook ... that cannabis use may harm the developing brain. Cannabis Use Correlates With Cognitive Decline The study participants ...

  2. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study

    PubMed Central

    2016-01-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ2 test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry. PMID:27051248

  3. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

    PubMed

    Park, Seon-Cheol; Sakong, Jeongkyu; Koo, Bon Hoon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

    2016-04-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry.

  4. Affective information processing in pregnancy and postpartum with and without major depression.

    PubMed

    Gollan, Jackie K; Hoxha, Denada; Getch, Sarah; Sankin, Lindsey; Michon, Ruth

    2013-04-30

    Adults with clinical depression exhibit systematic errors in their recognition and interpretation of affective stimuli. This study investigated the extent to which depression and phases of pregnancy and postpartum influence affective processing of positive and negative information, and the extent to which affective information processing in pregnancy predicts depressive symptoms in postpartum. Data were collected from 80 unmedicated women, diagnosed with major depressive disorder (MDD) or with no psychiatric disorder and between ages 18 and 44 years, during 32-36 weeks of pregnancy and during 6-8 weeks postpartum. All completed a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) Axis I review, symptom reports, and a computer task measuring affective information processing. Significant group differences were found in which postpartum women with major depression were less responsive to negative stimuli, with lower ratings of intensity and reactions to negative pictorial stimuli, compared with postpartum healthy women. Also, lower ratings of the intensity and reactions to negative stimuli during pregnancy among depressed women predicted postpartum depression severity, even after controlling for depressive severity and affect ratings in pregnancy. Blunted affective reactivity to negative stimuli is a characteristic of depression that was observed among depressed women during pregnancy and postpartum in our study.

  5. Strong family history and early onset of schizophrenia: about 2 families in Northern Nigeria

    PubMed Central

    Nuhu, Folorunsho Tajudeen; Eseigbe, Edwin Ehi; Issa, Baba Awoye; Gomina, Michael Omeiza

    2016-01-01

    Schizophrenia is a highly heritable psychotic disorder and high genetic loading is associated with early onset of the disease. The outcome of schizophrenia has also been linked with the age of onset as well as the presence of family history of the disease. Therefore families with patients with early onset Schizophrenia are subpopulations for genetic studies. We present 2 families with heavy genetic loading who have adolescents with schizophrenia. PMID:28154637

  6. High Throughput Sequencing of Germline and Tumor from Men With Early-Onset Metastatic Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    challenge, Dr. Tomlins has continued to develop state of the art technologies to use formalin-fixed paraffin-embedded (FFPE) prostate cancer specimens...men with early-onset, metastatic prostate cancer PRINCIPAL INVESTIGATOR: Kathleen A. Cooney, M.D. CONTRACTING ORGANIZATION...High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-13-1-0371 5c

  7. 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

  8. Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder.

    PubMed

    Toda, Hiroyuki; Inoue, Takeshi; Tsunoda, Tomoya; Nakai, Yukiei; Tanichi, Masaaki; Tanaka, Teppei; Hashimoto, Naoki; Takaesu, Yoshikazu; Nakagawa, Shin; Kitaichi, Yuji; Boku, Shuken; Tanabe, Hajime; Nibuya, Masashi; Yoshino, Aihide; Kusumi, Ichiro

    2016-02-28

    Previous studies have shown that various factors, such as genetic and environmental factors, contribute to the development of major depressive disorder (MDD). The aim of this study is to clarify how multiple factors, including affective temperaments, childhood abuse and adult life events, are involved in the severity of depressive symptoms in MDD. A total of 98 participants with MDD were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9 measuring the severity of depressive symptoms; Life Experiences Survey (LES) measuring negative and positive adult life events; Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring affective temperaments; and the Child Abuse and Trauma Scale (CATS) measuring childhood abuse. The data were analyzed using single and multiple regression analyses and structural equation modeling (SEM). The neglect score reported by CATS indirectly predicted the severity of depressive symptoms through affective temperaments measured by TEMPS-A in SEM. Four temperaments (depressive, cyclothymic, irritable, and anxious) directly predicted the severity of depressive symptoms. The negative change in the LES score also directly predicted severity. This study suggests that childhood abuse, especially neglect, indirectly increases the severity of depressive symptoms through increased scores of affective temperaments in MDD.

  9. Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty

    PubMed Central

    Satterthwaite, TD; Cook, PA; Bruce, SE; Conway, C; Mikkelsen, E; Satchell, E; Vandekar, SN; Durbin, T; Shinohara, RT; Sheline, YI

    2016-01-01

    Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n = 17; major depression, n = 38; and post-traumatic stress disorder, n = 50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories. PMID:26416545

  10. Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty.

    PubMed

    Satterthwaite, T D; Cook, P A; Bruce, S E; Conway, C; Mikkelsen, E; Satchell, E; Vandekar, S N; Durbin, T; Shinohara, R T; Sheline, Y I

    2016-07-01

    Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n=17; major depression, n=38; and post-traumatic stress disorder, n=50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories.

  11. Altered White Matter Microstructure in Adolescents with Major Depression: A Preliminary Study

    ERIC Educational Resources Information Center

    Cullen, Kathryn R.; Klimes-Dougan, Bonnie; Muetzel, Ryan; Mueller, Bryon A.; Camchong, Jazmin; Houri, Alaa; Kurma, Sanjiv; Lim, Kelvin O.

    2010-01-01

    Objective: Major depressive disorder (MDD) occurs frequently in adolescents, but the neurobiology of depression in youth is poorly understood. Structural neuroimaging studies in both adult and pediatric populations have implicated frontolimbic neural networks in the pathophysiology of MDD. Diffusion tensor imaging (DTI), which measures white…

  12. Recovery from Major Depressive Disorder among Female Adolescents: A Prospective Test of the Scar Hypothesis

    ERIC Educational Resources Information Center

    Beevers, Christopher G.; Rohde, Paul; Stice, Eric; Nolen-Hoeksema, Susan

    2007-01-01

    This study examined the psychosocial consequences of experiencing major depressive disorder (MDD). In a 7-year longitudinal study of 496 female adolescents, the authors identified 49 girls who experienced their first episode of MDD and then recovered. They were compared with a randomly selected group of 98 never depressed participants on 13…

  13. Psychosocial Treatments for Major Depression and Dysthymia in Older Adults: A Review of the Research Literature

    ERIC Educational Resources Information Center

    Zalaquett, Carlos P.; Stens, Andrea N.

    2006-01-01

    Older adults represent a growing segment of the population with the highest suicide rate and an increasing need of counseling services for major depression and dysthymia. The present study examined the literature with the purpose of identifying research addressing psychosocial treatments of depression in later life. A summary of treatments…

  14. Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Spring, Bonnie; Doran, Neal; Pagoto, Sherry; McChargue, Dennis; Cook, Jessica Werth; Bailey, Katherine; Crayton, John; Hedeker, Donald

    2007-01-01

    The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine…

  15. Correlates of Psychological Distress and Major Depressive Disorder among African American Men

    ERIC Educational Resources Information Center

    Lincoln, Karen D.; Taylor, Robert Joseph; Watkins, Daphne C.; Chatters, Linda M.

    2011-01-01

    This study examines the demographic correlates of depressive symptoms, serious psychological distress (SPD), and major depressive disorder (MDD; 12-month and lifetime prevalence) among a national sample of African American men. Analysis of the National Survey of American Life (NSAL) data set provides first-time substantiation of important…

  16. Self-compassion as an emotion regulation strategy in major depressive disorder.

    PubMed

    Diedrich, Alice; Grant, Michaela; Hofmann, Stefan G; Hiller, Wolfgang; Berking, Matthias

    2014-07-01

    Cognitive reappraisal and acceptance are two presumably adaptive emotion regulation strategies in depression. More recently, self-compassion has been discussed as another potentially effective strategy for coping with depression. In the present study, we compared the effectiveness of self-compassion with a waiting condition, reappraisal, and acceptance in a clinically depressed sample, and tested the hypothesis that the intensity of depressed mood would moderate the differential efficacy of these strategies. In an experimental design, we induced depressed mood at four points in time in 48 participants meeting criteria for major depressive disorder. After each mood induction, participants were instructed to wait, reappraise the situation, accept their negative emotions, or employ self-compassion to regulate their depressed mood. Self-ratings of depressed mood were assessed before and after each mood induction and regulation phase. Results showed that the reduction of depressed mood was significantly greater in the self-compassion condition than in the waiting condition. No significant differences were observed between the self-compassion and the reappraisal condition, and between the self-compassion and the acceptance condition in patients' mood ratings. However, the intensity of self-rated depressed mood at baseline was found to moderate the comparative effectiveness of self-compassion and reappraisal with a trend of self-compassion being more effective than reappraisal in high depressed mood at baseline. These findings support the use of self-compassion as another adaptive emotion regulation strategy for patients with major depressive disorder, especially for those suffering from high levels of depressed mood.

  17. Relationship of Premenstrual Syndrome and Premenstrual Dysphoric Disorder with Major Depression: Relevance to Clinical Practice

    PubMed Central

    Padhy, Susanta Kumar; Sarkar, Sidharth; Beherre, Prakash B.; Rathi, Rajesh; Panigrahi, Mahima; Patil, Pradeep Sriram

    2015-01-01

    Background: Premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD) and depressive disorder are fairly common; symptoms do overlap, often under-identified and under-emphasized, particularly in rural India. Objective: The objective was to assess the occurrence of PMS and PMDD in a sample of students and staff of a nursing college and to find their correlation with depression. Materials and Methods: A prospective cohort study; Tertiary Care Hospital in Rural India (Wardha, Maharashtra); 118 female nursing students or staff aged between 18 and 40 years, who were likely to stay within the institution for the study period. The participants were rated on Penn daily symptom report prospectively for a period of 3-month. Those who scored positive were applied diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV TR) criteria for PMDD; and were applied primary care evaluation of mental disorders depression screening followed by DSM-IV TR criteria for depression. Severity of depression was measured using Hamilton Depression Rating Scale. Results: Main outcome measures were frequency and severity of depression in individuals with PMS and PMDD and their clinical and sociodemographic correlation. The age range of the sample was 18-37 years. Some PMS symptoms were observed in 67%; diagnosis of PMDD in 10%; depressive symptoms in 28% of the sample. 46.4% of those with depressive symptoms had major depression. The diagnosis of major depression was significantly associated with the severity of PMS symptoms as well as the presence of PMDD. Conclusion: Premenstrual syndrome is present in a substantial proportion of young females. Concurrent depression is increased by the severity of PMS symptoms and the presence of PMDD. Gynecologist needs to screen such subjects for depression and refer to mental-health professional early, in routine clinical practice. PMID:25969600

  18. Disorder-specific volumetric brain difference in adolescent major depressive disorder and bipolar depression.

    PubMed

    MacMaster, Frank P; Carrey, Normand; Langevin, Lisa Marie; Jaworska, Natalia; Crawford, Susan

    2014-03-01

    Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7 ± 2.1 years), 14 BD subjects (16.0 ± 2.4 years) and 22 healthy controls (16.0 ± 2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F26,80 = 1.80, p = 0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p = 0.048) as well as right ACC white and gray matter volumes (p = 0.003; p = 0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p < 0.001; p = 0.015; p = 0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p = 0.019; p = 0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.

  19. Patterns of Adolescent Depression to Age 20: The Role of Maternal Depression and Youth Interpersonal Dysfunction

    ERIC Educational Resources Information Center

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle

    2008-01-01

    Considerable research has focused on youth depression, but further information is needed to characterize different patterns of onset and recurrence during adolescence. Four outcome groups by age 20 were defined (early onset-recurrent, early-onset-desisting, later-onset, never depressed) and compared on three variables predictive of youth…

  20. Major depressive disorder: mechanism-based prescribing for personalized medicine

    PubMed Central

    Saltiel, Philip F; Silvershein, Daniel I

    2015-01-01

    Individual patients with depression present with unique symptom clusters – before, during, and even after treatment. The prevalence of persistent, unresolved symptoms and their contribution to patient functioning and disease progression emphasize the importance of finding the right treatment choice at the onset and the utility of switching medications based on suboptimal responses. Our primary goal as clinicians is to improve patient function and quality of life. In fact, feelings of well-being and the return to premorbid levels of functioning are frequently rated by patients as being more important than symptom relief. However, functional improvements often lag behind resolution of mood, attributed in large part to persistent and functionally impairing symptoms – namely, fatigue, sleep/wake disturbance, and cognitive dysfunction. Thus, patient outcomes can be optimized by deconstructing each patient’s depressive profile to its component symptoms and specifically targeting those domains that differentially limit patient function. This article will provide an evidence-based framework within which clinicians may tailor pharmacotherapy to patient symptomatology for improved treatment outcomes. PMID:25848287

  1. Magnetization transfer imaging of suicidal patients with major depressive disorder.

    PubMed

    Chen, Ziqi; Zhang, Huawei; Jia, Zhiyun; Zhong, Jingjie; Huang, Xiaoqi; Du, Mingying; Chen, Lizhou; Kuang, Weihong; Sweeney, John A; Gong, Qiyong

    2015-04-08

    Magnetization transfer imaging (MTI) provides a quantitative measure of the macromolecular structural integrity of brain tissue, as represented by magnetization transfer ratio (MTR). In this study, we utilized MTI to identify biophysical alterations in MDD patients with a history of suicide attempts relative to MDD patients without such history. The participants were 36 medication-free MDD patients, with (N = 17) and without (N = 19) a history of a suicide attempt, and 28 healthy controls matched for age and gender. Whole brain voxel-based analysis was used to compare MTR across three groups and to analyze correlations with symptom severity and illness duration. We identified decreased MTR in left inferior parietal lobule and right superior parietal lobule in suicide attempters relative to both non-attempters and controls. Non-attempters also showed significantly reduced MTR in left inferior parietal lobule relative to controls, as well as an MTR reduction in left cerebellum. These abnormalities were not correlated with symptom severity or illness duration. Depressed patients with a history of suicide attempt showed bilateral abnormalities in parietal cortex compared to nonsuicidal depressed patients and healthy controls. Parietal lobe abnormalities might cause attentional dysfunction and impaired decision making to increase risk for suicidal behavior in MDD.

  2. A Review of the Role of Social Cognition in Major Depressive Disorder

    PubMed Central

    Weightman, Michael James; Air, Tracy Michele; Baune, Bernhard Theodor

    2014-01-01

    Background: Social cognition – the ability to identify, perceive, and interpret socially relevant information – is an important skill that plays a significant role in successful interpersonal functioning. Social cognitive performance is recognized to be impaired in several psychiatric conditions, but the relationship with major depressive disorder is less well understood. The aim of this review is to characterize the current understanding of: (i) the different domains of social cognition and a possible relationship with major depressive disorder, (ii) the clinical presentation of social cognition in acute and remitted depressive states, and (iii) the effect of severity of depression on social cognitive performance. Methods: Electronic databases were searched to identify clinical studies investigating social cognition in a major depressive disorder population, yielding 31 studies for this review. Results: Patients with major depressive disorder appear to interpret social cognitive stimuli differently to healthy controls: depressed individuals may interpret emotion through a mood-congruent bias and have difficulty with cognitive theory of mind tasks requiring interpretation of complex mental states. Social cognitive performance appears to be inversely associated with severity of depression, whilst the bias toward negative emotions persists even in remission. Some deficits may normalize following effective pharmacotherapy. Conclusions: The difficulties with social interaction observed in major depressive disorder may, at least in part, be due to an altered ability to correctly interpret emotional stimuli and mental states. These features seem to persist even in remission, although some may respond to intervention. Further research is required in this area to better understand the functional impact of these findings and the way in which targeted therapy could aid depressed individuals with social interactions. PMID:25566100

  3. The potential of transcranial photobiomodulation therapy for treatment of major depressive disorder.

    PubMed

    Salehpour, Farzad; Rasta, Seyed Hossein

    2017-02-23

    Major depressive disorder is a common debilitating mood disorder that affects quality of life. Prefrontal cortex abnormalities, an imbalance in neurotransmitters, neuroinflammation, and mitochondrial dysfunction are the major factors in the etiology of major depressive disorder. Despite the efficacy of pharmacotherapy in the treatment of major depressive disorder, 30%-40% of patients do not respond to antidepressants. Given this, exploring the alternative therapies for treatment or prevention of major depressive disorder has aroused interest among scientists. Transcranial photobiomodulation therapy is the use of low-power lasers and light-emitting diodes in the far-red to near-infrared optical region for stimulation of neuronal activities. This non-invasive modality improves the metabolic capacity of neurons due to more oxygen consumption and ATP production. Beneficial effects of transcranial photobiomodulation therapy in the wide range of neurological and psychological disorders have been already shown. In this review, we focus on some issues relating to the application of photobiomodulation therapy for major depressive disorder. There is some evidence that transcranial photobiomodulation therapy using near-infrared light on 10-Hz pulsed mode appears to be a hopeful technique for treatment of major depressive disorder. However, further studies are necessary to find the safety of this method and to determine its effective treatment protocol.

  4. Religious service attendance and spiritual well-being are differentially associated with risk of major depression

    PubMed Central

    Maselko, J.; Gilman, S. E.; Buka, S.

    2009-01-01

    Background The complex relationships between religiosity, spirituality and the risk of DSM-IV depression are not well understood. Method We investigated the independent influence of religious service attendance and two dimensions of spiritual well-being (religious and existential) on the lifetime risk of major depression. Data came from the New England Family Study (NEFS) cohort (n=918, mean age=39 years). Depression according to DSM-IV criteria was ascertained using structured diagnostic interviews. Odds ratios (ORs) for the associations between high, medium and low tertiles of spiritual well-being and for religious service attendance and the lifetime risk of depression were estimated using multiple logistic regression. Results Religious service attendance was associated with 30% lower odds of depression. In addition, individuals in the top tertile of existential well-being had a 70% lower odds of depression compared to individuals in the bottom tertile. Contrary to our original hypotheses, however, higher levels of religious well-being were associated with 1.5 times higher odds of depression. Conclusions Religious and existential well-being may be differentially associated with likelihood of depression. Given the complex interactions between religiosity and spirituality dimensions in relation to risk of major depression, the reliance on a single domain measure of religiosity or spirituality (e.g. religious service attendance) in research or clinical settings is discouraged. PMID:18834554

  5. Effects of ipsapirone on plasma cortisol and body temperature in major depression.

    PubMed

    Meltzer, H Y; Maes, M

    1995-10-01

    Major depressed patients have been reported to exhibit significantly attenuated hypothermic responses to ipsapirone, a serotonin (5-HT)-1A partial agonist, compared to normal controls. This study further investigated the cortisol and temperature responses to ipsapirone (0.5 mg/kg orally) and placebo in 20 normal volunteers and 12 major depressed patients. Both plasma cortisol and temperature were measured every 30 min before ipsapirone or placebo administration until 180 min post administration. Ipsapirone administration produced a significant increase in plasma cortisol levels as well as hypothermia. Major depressed patients showed significantly blunted ipsapirone-induced cortisol responses compared to normal controls. No significant differences in ipsapirone-induced hypothermic responses were found between major depressed patients and normal controls.

  6. Pharmacology Update on Chronic Obstructive Pulmonary Disease, Rheumatoid Arthritis, and Major Depression.

    PubMed

    Weatherspoon, Deborah; Weatherspoon, Christopher A; Abbott, Brianna

    2015-12-01

    This article presents a brief review and summarizes current therapies for the treatment of chronic obstructive pulmonary disease, major depression, and rheumatoid arthritis. One new pharmaceutical agent is highlighted for each of the topics.

  7. Major Depressive Episodes and Work Stress: Results From a National Population Survey

    PubMed Central

    Blackmore, Emma Robertson; Stansfeld, Stephen A.; Weller, Iris; Munce, Sarah; Zagorski, Brandon M.; Stewart, Donna E.

    2007-01-01

    Objectives. We determined the proportion of workers meeting criteria for major depressive episodes in the past year and examined the association between psychosocial work-stress variables and these episodes. Methods. Data were derived from the Canadian Community Health Survey 1.2, a population-based survey of 24324 employed, community-dwelling individuals conducted in 2002. We assessed depressive episodes using the Composite International Diagnostic Interview. Results. Of the original sample, 4.6% (weighted n=745948) met criteria for major depressive episodes. High job strain was significantly associated with depression among men (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.29, 4.37), and lack of social support at work was significantly associated with depression in both genders (men, OR=2.70; 95% CI=1.55, 4.71; women, OR=2.37; 95% CI=1.71, 3.29). Women with low levels of decision authority were more likely to have depression (OR=1.59; 95% CI=1.06, 2.39) than were women with high levels of authority. Conclusions. A significant proportion of the workforce experienced major depressive episodes in the year preceding our study. Gender differences appear to affect work-stress factors that increase risk for depression. Prevention strategies need to be developed with employers and employee organizations to address work organization and to increase social support. PMID:17901431

  8. Mirtazapine in Comorbid Major Depression and Alcohol Dependence: An Open-Label Trial

    PubMed Central

    Cornelius, Jack R.; Douaihy, Antoine B.; Clark, Duncan B.; Chung, Tammy; Wood, D. Scott; Daley, Dennis

    2012-01-01

    Objective This was a first pilot study evaluating the acute phase (8-week) efficacy of the antidepressant medication mirtazapine for the treatment of depressive symptoms and drinking of subjects with comorbid major depressive disorder and alcohol dependence (MDD/AD). We hypothesized that mirtazapine would demonstrate within-group efficacy for the treatment of both depressive symptoms and drinking in these subjects. Methods We conducted a first open label study of the second generation antidepressant mirtazapine in 12 adult outpatient subjects with comorbid major depressive disorder/alcohol dependence. The pharmacological profile of that medication is unique among antidepressants, unrelated to tricyclics or selective serotonin reuptake inhibitors. Results Mirtazapine was well tolerated in this treatment population. Self-reported depressive symptoms decreased from 31.8 to 8.3 on the Beck Depression Inventory, a 74.0% decrease (p<0.001), and drinking decreased from 33.9 to 13.3 drinks per week, a 60.8% decrease (p<0.05). None of the subjects were employed full-time at baseline, but 9 of the 12 (75%) were employed full-time at end-of-study. Conclusions These preliminary findings suggest efficacy for mirtazapine for treating both the depressive symptoms and excessive alcohol use of comorbid major depressive disorder and alcohol dependence. Double-blind studies are warranted to further clarify the efficacy of mirtazapine in this population. PMID:23230395

  9. Is blunted cardiovascular reactivity in depression mood-state dependent? A comparison of major depressive disorder remitted depression and healthy controls.

    PubMed

    Salomon, Kristen; Bylsma, Lauren M; White, Kristi E; Panaite, Vanessa; Rottenberg, Jonathan

    2013-10-01

    Prior work has repeatedly demonstrated that people who have current major depression exhibit blunted cardiovascular reactivity to acute stressors (e.g., Salomon et al., 2009). A key question regards the psychobiological basis for these deficits, including whether such deficits are depressed mood-state dependent or whether these effects are trait-like and are observed outside of depression episodes in vulnerable individuals. To examine this issue, we assessed cardiovascular reactivity to a speech stressor task and a forehead cold pressor in 50 individuals with current major depressive disorder (MDD), 25 with remitted major depression (RMD), and 45 healthy controls. Heart rate (HR), blood pressure and impedance cardiography were assessed and analyses controlled for BMI and sex. Significant group effects were found for SBP, HR, and PEP for the speech preparation period and HR, CO, and PEP during the speech. For each of these parameters, only the MDD group exhibited attenuated reactivity as well as impaired SBP recovery. Reactivity and recovery in the RMD group more closely resembled the healthy controls. Speeches given by the MDD group were rated as less persuasive than the RMD or healthy controls' speeches. No significant differences were found for the cold pressor. Blunted cardiovascular reactivity and impaired recovery in current major depression may be mood-state dependent phenomena and may be more reflective of motivational deficits than deficits in the physiological integrity of the cardiovascular system.

  10. Does family history of depression predict major depression in midlife women? Study of Women's Health Across the Nation Mental Health Study (SWAN MHS).

    PubMed

    Colvin, Alicia; Richardson, Gale A; Cyranowski, Jill M; Youk, Ada; Bromberger, Joyce T

    2014-08-01

    This study aims to determine whether family history of depression predicts major depression in midlife women independent of psychosocial and health profiles at midlife. Participants were 303 African American and Caucasian women (42-52 years at baseline) recruited into the Study of Women's Health Across the Nation (SWAN) and the Women's Mental Health Study (MHS) in Pittsburgh. Major depression was assessed annually with the Structured Clinical Interview for DSM-IV. Family mental health history was collected at the ninth or tenth follow-up. Multivariable logistic regression was used to determine whether family history of depression predicted major depression in midlife, adjusting for covariates. The odds of experiencing major depression during the study were three times greater for those with a family history than for those without a family history (OR = 3.22, 95% CI = 1.95-5.31). Family history predicted depression (OR = 2.67, 95% CI = 1.50-4.78) after adjusting for lifetime history of depression, age, trait anxiety, chronic medical conditions, and stressful life events. In analyses stratified by lifetime history of depression, family history significantly predicted depression only among women with a lifetime history of depression. Family history of depression predicts major depression in midlife women generally, but particularly in those with a lifetime history of depression prior to midlife.

  11. Unexplained Painful Physical Symptoms in Patients with Major Depressive Disorder: Prevalence, Pathophysiology and Management.

    PubMed

    Jaracz, Jan; Gattner, Karolina; Jaracz, Krystyna; Górna, Krystyna

    2016-04-01

    Patients with major depression often report pain. In this article, we review the current literature regarding the prevalence and consequences, as well as the pathophysiology, of unexplained painful physical symptoms (UPPS) in patients with major depressive disorder (MDD). UPPS are experienced by approximately two-thirds of depressed patients. The presence of UPPS makes a correct diagnosis of depression more difficult. Moreover, UPPS are a predictor of a poor response to treatment and a more chronic course of depression. Pain, in the course of depression, also has a negative impact on functioning and quality of life. Frequent comorbidity of depression and UPPS has inspired the formulation of an hypothesis regarding a shared neurobiological mechanism of both conditions. Evidence from neuroimaging studies has shown that frontal-limbic dysfunction in depression may explain abnormal pain processing, leading to the presence of UPPS. Increased levels of proinflamatory cytokines and substance P in patients with MDD may also clarify the pathophysiology of UPPS. Finally, dysfunction of the descending serotonergic and noradrenergic pathways that normally suppress ascending sensations has been proposed as a core mechanism of UPPS. Psychological factors such as catastrophizing also play a role in both depression and chronic pain. Therefore, pharmacological treatment and/or cognitive therapy are recommended in the treatment of depression with UPPS. Some data suggest that serotonin and noradrenaline reuptake inhibitors (SNRIs) are more effective than selective serotonin reuptake inhibitors (SSRIs) in the alleviation of depression and UPPS. However, the pooled analysis of eight randomised clinical trials showed similar efficacy of duloxetine (an SNRI) and paroxetine (an SSRI) in reducing UPPS in depression. Further integrative studies examining genetic factors (e.g. polymorphisms of genes for interleukins, serotonin transporter and receptors), molecular factors (e.g. cytokines

  12. Multi-Scale Motility Amplitude Associated with Suicidal Thoughts in Major Depression

    PubMed Central

    Indic, Premananda; Murray, Greg; Maggini, Carlo; Amore, Mario; Meschi, Tiziana; Borghi, Loris; Baldessarini, Ross J.; Salvatore, Paola

    2012-01-01

    Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r =  –0.61 with all subjects and r =  –0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians. PMID:22701706

  13. The impact of cognitive challenges in major depression: the role of the primary care physician.

    PubMed

    Mattingly, Gregory; Anderson, Richard H; Mattingly, Stephen G; Anderson, Elizabeth Q

    2016-09-01

    Nearly 1 in 5 Americans will struggle with major depression in their lives; some will have recurring bouts. Recent psychiatric research has given new attention to the prevalence of cognitive deficits in major depression and the impact such deficits have on remission and overall life functioning. When depression is partially treated i.e., leaving residual symptoms, patients have higher rates of relapse and lower functional outcomes. Impaired cognitive functioning is a frequent residual symptom, persisting in about 45% of patients even when emotional symptoms have improved, and results in a disproportionate share of the functional impairment, particularly in the workplace. Patients with depression have disrupted circuitry in brain regions responsible for cognition and it is therefore important to screen depressed patients for cognitive as well as emotional symptoms. Cognitive dysfunction should be evaluated in every mood disordered patient with validated self-report scales such as the Patient Health Questionnaire-9 or the Beck Depression Inventory and objective measures of cognitive function are also very very useful. Two easily administered tests are the Trails B Test and the Digit Symbol Substitution Test. Each take less than two minutes and measure working memory, executive function, and processing speed and can track cognitive improvement in depressed patients. Treatment of cognitive dysfunction in major depression is complicated by the 'serotonin conundrum': SSRI's frequently do not treat to full remission, and can cause cognitive blunting-actually adding to cognitive problems. Based on recent data including results from a recently completed meta-analysis by McIntyre and colleagues, an evidence-based algorithm for treating cognitive symptoms in depression is presented. A hierarchy of antidepressants and augmentation strategies based on the best available evidence is discussed. In conclusion, cognitive symptoms in major depressive disorder have been recognized as

  14. Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder.

    PubMed

    Dunlop, Boadie W; Kelley, Mary E; Mletzko, Tanja C; Velasquez, Cristina M; Craighead, W Edward; Mayberg, Helen S

    2012-03-01

    Previous studies suggest that individual preferences for medication- or psychotherapy-based treatments for depression may affect outcomes in clinical trials that compare these two forms of treatment. We assessed patients' beliefs about the causes of their depression, their preferred treatment, and strength of that preference in 80 patients participating in a 12-week clinical trial evaluating neuroimaging predictors of response to cognitive behavior therapy (CBT) or escitalopram. Forty-five patients expressed a preference for one of the 2 treatments, but being matched to preference did not influence remission or completion rates. Medication-preferring patients were more likely to terminate the trial early, regardless of treatment received. CBT-preferring patients rarely endorsed unknown causes for their depression, and medication-preferring patients were highly unlikely to identify pessimistic attitudes as a source of their depression. Among patients willing to be randomized to treatment, preference does not appear to strongly influence outcome. Specific preferences for CBT or medication may reflect differing conceptualizations about depressive illness, knowledge of which may enhance treatment retention and efficacy.

  15. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder.

    PubMed

    Grosse, Laura; Carvalho, Livia A; Wijkhuijs, Annemarie J M; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A; Arolt, Volker

    2015-02-01

    Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 ± 12 years) and 57 healthy controls (HC; 31 ± 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)α and GRβ genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MDD patients. Increased monocyte gene expression and decreased GRα/β ratio were only present in MDD patients aged ⩾ 28 years. Post hoc analyses of monocyte immune activation in patients <28 years showed two subgroups: a subgroup with a severe course of depression (recurrent type, onset <15 years) - additionally characterized by panic/arousal symptoms and childhood trauma - that had a monocyte gene expression similar to HC, and a second subgroup with a milder course of the disorder (73% first episode depression, onset ⩾15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older.

  16. Asperger syndrome and early-onset schizophrenia associated with a novel MECP2 deleterious missense variant.

    PubMed

    Curie, Aurore; Lesca, Gaëtan; Bussy, Gérald; Manificat, Sabine; Arnaud, Valérie; Gonzalez, Sibylle; Revol, Olivier; Calender, Alain; Gérard, Daniel; des Portes, Vincent

    2017-02-27

    Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males. A neuropsychiatric phenotype without intellectual disability is uncommon in patients with MECP2 deleterious variants. We report on two dizygotic twins with an MECP2-related psychiatric disorder without intellectual disability. Neuropsychological and psychiatric phenotype assessments were performed, and a genetic analysis was carried out. Both patients fulfilled the Pervasive Developmental Disorder criteria on Autism Diagnostic Observation Schedule and Asperger syndrome criteria on Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). One patient developed early-onset schizophrenia (DSM-IV criteria) with two acute psychotic episodes, the latest one following corticosteroids and sodium valproate intake, with major hyperammonemia. A novel MECP2 gene transversion c.491 G>T [p.(Ser164Ile)] was found in both twins. Pathogenicity of this variant was considered on the basis of strong clinical and molecular data. The underlying molecular basis of neuropsychiatric disorders may have important consequences on genetic counseling and therapeutic strategies.

  17. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features

    PubMed Central

    Lessel, Davor; Vaz, Bruno; Halder, Swagata; Lockhart, Paul J; Marinovic-Terzic, Ivana; Lopez-Mosqueda, Jaime; Philipp, Melanie; Sim, Joe C H; Smith, Katherine R; Oehler, Judith; Cabrera, Elisa; Freire, Raimundo; Pope, Kate; Nahid, Amsha; Norris, Fiona; Leventer, Richard J; Delatycki, Martin B; Barbi, Gotthold; von Ameln, Simon; Högel, Josef; Degoricija, Marina; Fertig, Regina; Burkhalter, Martin D; Hofmann, Kay; Thiele, Holger; Altmüller, Janine; Nürnberg, Gudrun; Nürnberg, Peter; Bahlo, Melanie; Martin, George M; Aalfs, Cora M; Oshima, Junko; Terzic, Janos; Amor, David J; Dikic, Ivan; Ramadan, Kristijan; Kubisch, Christian

    2015-01-01

    Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1)1–7 in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis1–7. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma. PMID:25261934

  18. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

    PubMed

    Milner, Joshua D; Vogel, Tiphanie P; Forbes, Lisa; Ma, Chi A; Stray-Pedersen, Asbjørg; Niemela, Julie E; Lyons, Jonathan J; Engelhardt, Karin R; Zhang, Yu; Topcagic, Nermina; Roberson, Elisha D O; Matthews, Helen; Verbsky, James W; Dasu, Trivikram; Vargas-Hernandez, Alexander; Varghese, Nidhy; McClain, Kenneth L; Karam, Lina B; Nahmod, Karen; Makedonas, George; Mace, Emily M; Sorte, Hanne S; Perminow, Gøri; Rao, V Koneti; O'Connell, Michael P; Price, Susan; Su, Helen C; Butrick, Morgan; McElwee, Joshua; Hughes, Jason D; Willet, Joseph; Swan, David; Xu, Yaobo; Santibanez-Koref, Mauro; Slowik, Voytek; Dinwiddie, Darrell L; Ciaccio, Christina E; Saunders, Carol J; Septer, Seth; Kingsmore, Stephen F; White, Andrew J; Cant, Andrew J; Hambleton, Sophie; Cooper, Megan A

    2015-01-22

    Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350.

  19. Suicidal risk factors of recurrent major depression in Han Chinese women.

    PubMed

    Zhu, Yuzhang; Zhang, Hongni; Shi, Shenxun; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth Seedman; Flint, Jonathan; Liu, Ying

    2013-01-01

    The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women.

  20. PERSONAL HISTORY OF MAJOR DEPRESSION MAY PUT WOMEN AT RISK FOR PREMENSTRUAL DYSPHORIC SYMPTOMATOLOGY

    PubMed Central

    Accortt, Eynav E.; Kogan, Anya V.; Allen, John J.B.

    2013-01-01

    Background Premenstrual dysphoric disorder (PMDD) is a chronic condition that significantly affects a woman’s well-being on a monthly basis. Although co-occurrence of PMDD and major depressive disorder (MDD) is common, most studies examine whether women with PMDD are at risk for depression and investigations of PMDD in depressed women are scant. Therefore, the present study examined rates of PMDD in young depressed women. Methods PMDD was assessed using a structured clinical interview (SCID-PMDD) in a sample of 164 young women with (n=85) and without (n=79) any history of depression. Results Rates of PMDD were elevated among women with MDD in this sample. This result held true regardless of participants’ MDD status (current, lifetime or past history-only symptoms of MDD) and regardless of whether all or most DSM-IV-TR PMDD criteria were met. Limitations Sample size in the present study was relatively small, and daily diary data were not available to confirm a PMDD diagnosis. Conclusions The current study highlights the need for clinicians to assess for PMDD in young female patients with major depression. Depressed women experiencing the added physical and psychological burden of PMDD may have a more severe disease course, and future studies will need to identify appropriate treatments for this subset of depressed women. PMID:23800446

  1. Prevalence and correlates of DSM-5 major depressive and related disorders in the community.

    PubMed

    Vandeleur, Caroline L; Fassassi, Sylfa; Castelao, Enrique; Glaus, Jennifer; Strippoli, Marie-Pierre F; Lasserre, Aurélie M; Rudaz, Dominique; Gebreab, Sirak; Pistis, Giorgio; Aubry, Jean-Michel; Angst, Jules; Preisig, Martin

    2017-04-01

    Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category.

  2. Deficits in sustaining reward responses in subsyndromal and syndromal major depression.

    PubMed

    Liu, Wen-hua; Chan, Raymond C K; Wang, Ling-zhi; Huang, Jia; Cheung, Eric F C; Gong, Qi-yong; Gollan, Jackie K

    2011-06-01

    Preliminary findings suggest a reduction in capacity to sustain reward responses in major depression. However, relatively little is known about the stability of reward learning over time and the effect of stress on reward responses in depressed individuals. This study aimed to evaluate sustained behaviour to maximize reward in the context of known reinforcement contingencies and to evaluate the extent to which stress influences such behaviour in clinically depressed patients (n=43), subsyndromally depressed individuals (n=43), and healthy controls (n=44). A probabilistic reward learning task with contingencies known to participants was used to evaluate the change of reward response over time in both 'stress' and 'non-stress' conditions. Stress was induced by salient negative feedback during the task performance. Questionnaires capturing subjective affect were also administered to all participants after completion of the task. Response bias to the stimulus signaling greater reward decreased significantly over time in both subsyndromally and clinically depressed participants, but not in healthy controls. Healthy controls demonstrated a trend of dysfunctional reward processing under the stress condition. Moreover, in the stress condition, the deficit in sustaining behaviour to maximize reward was associated with subjective rating of pleasure in participants with either subsyndromal depression or major depression. These findings suggest that individuals with depression have difficulty sustaining behaviour during a known reinforcement schedule. Participants with anhedonic symptoms are even less likely to sustain behaviour to maximize reward under stress.

  3. Efficacy of vilazodone on anxiety symptoms in patients with major depressive disorder.

    PubMed

    Thase, Michael E; Chen, Dalei; Edwards, John; Ruth, Adam

    2014-11-01

    Anxiety symptoms are prevalent in patients with major depressive disorder. A post-hoc analysis of two phase III trials was conducted to evaluate the efficacy of vilazodone on depression-related anxiety. Using the 17-item Hamilton Depression Rating Scale (HAMD17) Anxiety/Somatization subscale, patients were classified as anxious or nonanxious. Improvements in depressive symptoms were based on least squares mean changes in HAMD17 and Montgomery-Asberg Depression Rating Scale total scores. Anxiety symptoms in the anxious subgroup were evaluated using Hamilton Anxiety Rating Scale (HAMA) total and subscale (Psychic Anxiety, Somatic Anxiety) scores, HAMD17 Anxiety/Somatization subscale and item (Psychic Anxiety, Somatic Anxiety) scores, and the Montgomery-Asberg Depression Rating Scale Inner Tension item score. Most of the pooled study population [82.0% (708/863)] was classified with anxious depression. After 8 weeks of treatment, least squares mean differences between vilazodone and placebo for changes in HAMA total and HAMD17 Anxiety/Somatization subscale scores were -1.82 (95% confidence interval -2.81 to -0.83; P<0.001) and -0.75 (95% confidence interval -1.17 to -0.32; P<0.001), respectively. Statistically significant improvements with vilazodone were also found on all other anxiety-related measures, except the HAMA Somatic Anxiety subscale. Vilazodone may be effective in treating patients with major depressive disorder who exhibit somatic and/or psychic symptoms of anxiety.

  4. Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires

    PubMed Central

    Fischer, Anja; Fischer, Marcus; Nicholls, Robert A; Lau, Stephanie; Poettgen, Jana; Patas, Kostas; Heesen, Christoph; Gold, Stefan M

    2015-01-01

    Objective Multiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high-risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30-item version of the Inventory of Depressive Symptomatology Self-Rated (IDS-SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview. Methods Patients reporting depressive symptoms completed the BDI, the IDS-SR30 and underwent diagnostic assessment (Mini International Neuropsychiatric Interview, M.I.N.I.). Receiver-Operating Characteristic analyses were performed, providing error estimates and false-positive/negative rates of suggested thresholds. Results Data from n = 31 MS patients were available. BDI and IDS-SR30 total score were significantly correlated (r = 0.82). The IDS-SR30total score, cognitive subscore, and BDI showed excellent to good accuracy (area under the curve (AUC) 0.86, 0.91, and 0.85, respectively). Conclusion Both the IDS-SR30 and the BDI are useful to quantify depressive symptoms showing good sensitivity and specificity. The IDS-SR30 cognitive subscale may be useful as a screening tool and to quantify affective/cognitive depressive symptomatology. PMID:26445703

  5. Cognitive conflicts in major depression: Between desired change and personal coherence

    PubMed Central

    Feixas, Guillem; Montesano, Adrián; Compañ, Victoria; Salla, Marta; Dada, Gloria; Pucurull, Olga; Trujillo, Adriana; Paz, Clara; Muñoz, Dámaris; Gasol, Miquel; Saúl, Luis Ángel; Lana, Fernando; Bros, Ignasi; Ribeiro, Eugenia; Winter, David; Carrera-Fernández, María Jesús; Guàrdia, Joan

    2014-01-01

    Objectives The notion of intrapsychic conflict has been present in psychopathology for more than a century within different theoretical orientations. However, internal conflicts have not received enough empirical attention, nor has their importance in depression been fully elaborated. This study is based on the notion of cognitive conflict, understood as implicative dilemma (ID), and on a new way of identifying these conflicts by means of the Repertory Grid Technique. Our aim was to explore the relevance of cognitive conflicts among depressive patients. Design Comparison between persons with a diagnosis of major depressive disorder and community controls. Methods A total of 161 patients with major depression and 110 non-depressed participants were assessed for presence of IDs and level of symptom severity. The content of these cognitive conflicts was also analysed. Results Repertory grid analysis indicated conflict (presence of ID/s) in a greater proportion of depressive patients than in controls. Taking only those grids with conflict, the average number of IDs per person was higher in the depression group. In addition, participants with cognitive conflicts displayed higher symptom severity. Within the clinical sample, patients with IDs presented lower levels of global functioning and a more frequent history of suicide attempts. Conclusions Cognitive conflicts were more prevalent in depressive patients and were associated with clinical severity. Conflict assessment at pre-therapy could aid in treatment planning to fit patient characteristics. Practitioner points Internal conflicts have been postulated in clinical psychology for a long time but there is little evidence about its relevance due to the lack of methods to measure them. We developed a method for identifying conflicts using the Repertory Grid Technique. Depressive patients have higher presence and number of conflicts than controls. Conflicts (implicative dilemmas) can be a new target for intervention in

  6. Measures of the DSM-5 mixed-features specifier of major depressive disorder.

    PubMed

    Zimmerman, Mark

    2017-01-12

    During the past two decades, a number of studies have found that depressed patients frequently have manic symptoms intermixed with depressive symptoms. While the frequency of mixed syndromes are more common in bipolar than in unipolar depressives, mixed states are also common in patients with major depressive disorder. The admixture of symptoms may be evident when depressed patients present for treatment, or they may emerge during ongoing treatment. In some patients, treatment with antidepressant medication might precipitate the emergence of mixed states. It would therefore be useful to systematically inquire into the presence of manic/hypomanic symptoms in depressed patients. We can anticipate that increased attention will likely be given to mixed depression because of changes in the DSM-5. In the present article, I review instruments that have been utilized to assess the presence and severity of manic symptoms and therefore could be potentially used to identify the DSM-5 mixed-features specifier in depressed patients and to evaluate the course and outcome of treatment. In choosing which measure to use, clinicians and researchers should consider whether the measure assesses both depression and mania/hypomania, assesses all or only some of the DSM-5 criteria for the mixed-features specifier, or assesses manic/hypomanic symptoms that are not part of the DSM-5 definition. Feasibility, more so than reliability and validity, will likely determine whether these measures are incorporated into routine clinical practice.

  7. Complementary and alternative medicine for the treatment of major depressive disorder

    PubMed Central

    Nahas, Richard; Sheikh, Osmaan

    2011-01-01

    Abstract Objective To review the clinical evidence supporting complementary and alternative medicine interventions for treating major depressive disorder. Quality of evidence PubMed was searched from January 1966 to February 2010 using the term depressive disorder in combination with St John’s wort, S-adenosylmethionine (SAM-e), exercise, acupuncture, omega-3 fatty acids, and folate. Only relevant human trials were selected. Main message In a large meta-analysis, St John’s wort was found to be equivalent to antidepressant drugs with fewer side effects. Exercise reduced depressive scores in 3 meta-analyses. Omega-3 fatty acids reduced depressive scores in a meta-analysis of 16 trials, but publication bias was identified. Oral SAM-e monotherapy reduced depressive scores in 4 of 5 small randomized controlled trials. Folate deficiency is associated with more severe and refractory depression, and supplementation reduced depressive scores in 2 of 3 randomized controlled trials. Acupuncture demonstrated limited efficacy in 1 meta-analysis and 5 other trials. Conclusion St John’s wort and regular exercise appear effective in the treatment of depression. Acupuncture appears ineffective for depression, but it might offer other health benefits. Other promising therapies include SAM-e, omega-3 fatty acid, and folic acid supplementation in selected patients; further study is warranted. PMID:21673208

  8. Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Hanusa, Barbara H.; Moses-Kolko, Eydie L.; Bogen, Debra L.; Hunker, Diane F.; Perel, James M.; Jones-Ivy, Sonya; Bodnar, Lisa M.; Singer, Lynn T.

    2015-01-01

    Objective Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. Method This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. Results Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. Conclusions For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%. PMID:19289451

  9. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

    PubMed Central

    2010-01-01

    Background The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. Methods We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity. Results The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05). Conclusions As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the

  10. Meditation for Depression: A Systematic Review of Mindfulness-Based Cognitive Therapy for Major Depressive Disorder

    DTIC Science & Technology

    2015-10-01

    clinical trial: a latent variable structural equation modeling approach. Psychological Medicine, 43(8), 1611-1623. doi: 10.1017/s0033291712002772...Colaiaco, Patricia M. Herman RAND NSRD RR-1138 -OSD October 2015 Defense Centers of Excellence for Psychological Health and Traumatic Brain...release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Depression is a prevalent psychological health condition and clinical

  11. Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population.

    PubMed

    Wen, Zujia; Chen, Jianhua; Khan, Raja Amjad Waheed; Song, Zhijian; Wang, Meng; Li, Zhiqiang; Shen, Jiawei; Li, Wenjin; Shi, Yongyong

    2016-04-01

    Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye  = 0.015) and rs4512342 (Pallele  = 0.03, Pgenotye  = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye  = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population.

  12. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    PubMed Central

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  13. Symptoms of Major Depression in a Sample of Fathers of Infants: Sociodemographic Correlates and Links to Father Involvement

    ERIC Educational Resources Information Center

    Bronte-Tinkew, Jacinta; Moore, Kristin A.; Matthews, Gregory; Carrano, Jennifer

    2007-01-01

    Depression has been extensively studied for mothers but not for fathers. This study examines the sociodemographic correlates of symptoms of depression and how depression is associated with father involvement using the Composite International Diagnostic Interview-Short Form (CIDI-SF) for major depression. The study uses a sample of 2,139 resident…

  14. Intergenerational Transmission of Internalizing Problems: Effects of Parental and Grandparental Major Depressive Disorder on Child Behavior

    PubMed Central

    Pettit, Jeremy W.; Olino, Thomas M.; Roberts, Robert E.; Seeley, John R.; Lewinsohn, Peter M.

    2008-01-01

    Effects of lifetime histories of grandparental (G1) and parental (G2) major depressive disorder (MDD) on children's (G3) internalizing problems were investigated among 267 G3 children (ages 2–18 years) who received Child Behavior Checklist (CBCL) ratings and had diagnostic data available on 267 biological G2 parents and 527 biological G1 grandparents. Results indicated that G1 MDD conferred risk for G2 MDD, but not for G3 CBCL scores. G2 MDD predicted higher G3 Internalizing and Anxious/Depressed scores. Also, there was an interaction between G1 MDD and G2 MDD in predicting higher G3 Anxious/Depressed scores such that scores were highest among children with both depressed parents and grandparents. These effects were robust to statistical adjustments for status variables and parental relationship measures but not to adjustment for concurrent parental depressive symptoms. PMID:18645754

  15. Subchronic treatment with aldosterone induces depression-like behaviours and gene expression changes relevant to major depressive disorder.

    PubMed

    Hlavacova, Natasa; Wes, Paul D; Ondrejcakova, Maria; Flynn, Marianne E; Poundstone, Patricia K; Babic, Stanislav; Murck, Harald; Jezova, Daniela

    2012-03-01

    The potential role of aldosterone in the pathophysiology of depression is unclear. The aim of this study was to test the hypothesis that prolonged elevation of circulating aldosterone induces depression-like behaviour accompanied by disease-relevant changes in gene expression in the hippocampus. Subchronic (2-wk) treatment with aldosterone (2 μg/100 g body weight per day) or vehicle via subcutaneous osmotic minipumps was used to induce hyperaldosteronism in male rats. All rats (n = 20/treatment group) underwent a modified sucrose preference test. Half of the animals from each treatment group were exposed to the forced swim test (FST), which served both as a tool to assess depression-like behaviour and as a stress stimulus. Affymetrix microarray analysis was used to screen the entire rat genome for gene expression changes in the hippocampus. Aldosterone treatment induced an anhedonic state manifested by decreased sucrose preference. In the FST, depressogenic action of aldosterone was manifested by decreased latency to immobility and increased time spent immobile. Aldosterone treatment resulted in transcriptional changes of genes in the hippocampus involved in inflammation, glutamatergic activity, and synaptic and neuritic remodelling. Furthermore, aldosterone-regulated genes substantially overlapped with genes affected by stress in the FST. This study demonstrates the existence of a causal relationship between the hyperaldosteronism and depressive behaviour. In addition, aldosterone treatment induced changes in gene expression that may be relevant to the aetiology of major depressive disorder. Subchronic treatment with aldosterone represents a new animal model of depression, which may contribute to the development of novel targets for the treatment of depression.

  16. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms.

    PubMed

    Owens, Matthew; Herbert, Joe; Jones, Peter B; Sahakian, Barbara J; Wilkinson, Paul O; Dunn, Valerie J; Croudace, Timothy J; Goodyer, Ian M

    2014-03-04

    Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys.

  17. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms

    PubMed Central

    Owens, Matthew; Herbert, Joe; Jones, Peter B.; Sahakian, Barbara J.; Wilkinson, Paul O.; Dunn, Valerie J.; Croudace, Timothy J.; Goodyer, Ian M.

    2014-01-01

    Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys. PMID:24550453

  18. Structural Asymmetry of Dorsolateral Prefrontal Cortex Correlates with Depressive Symptoms: Evidence from Healthy Individuals and Patients with Major Depressive Disorder.

    PubMed

    Liu, Wei; Mao, Yu; Wei, Dongtao; Yang, Junyi; Du, Xue; Xie, Peng; Qiu, Jiang

    2016-06-01

    In this study, we investigated the role of structural asymmetry of the dorsolateral prefrontal cortex (DLPFC) in the continuum of depression from healthy individuals to patients. Structural magnetic resonance imaging was performed in 70 patients with major depressive disorder (MDD), 49 matched controls, and 349 healthy university students to calculate structural asymmetry indexes of the DLPFC. First-episode, treatment-naive MDD patients showed a relatively lower asymmetry index than healthy controls, and their asymmetry index was negatively correlated with the depressive symptoms. This abnormality was normalized by antidepressants in medicated MDD patients. Furthermore, the asymmetry index was negatively correlated with the depressive symptoms in university students; this was replicated at two time points in a subgroup of students, suggesting good test-retest reliability. Our findings are consistent with previous studies that support the imbalance hypothesis of MDD and suggest a potential structural basis underlying the functional asymmetry of the DLPFC in depression. In future, the structural index of the DLPFC may become a potential biomarker to evaluate individuals' risk for the onset of MDD.

  19. Temperament, personality, and treatment outcome in major depression: a 6-month preliminary prospective study

    PubMed Central

    Kudo, Yuka; Nakagawa, Atsuo; Wake, Taisei; Ishikawa, Natsumi; Kurata, Chika; Nakahara, Mizuki; Nojima, Teruo; Mimura, Masaru

    2017-01-01

    Background Despite available treatments, major depression is a highly heterogeneous disorder, which leads to problems in classification and treatment specificity. Previous studies have reported that personality traits predict and influence the course and treatment response of depression. The Temperament and Personality Questionnaire (T&P) assesses eight major constructs of personality traits observed in those who develop depression. The aim of this study was to investigate the influence of T&P’s eight constructs on the treatment outcome of depressed patients. Patients and methods A preliminary 6-month prospective study was conducted with a sample of 51 adult patients with a diagnosis of major depressive disorder (MDD) without remarkable psychomotor disturbance using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. All patients received comprehensive assessment including the T&P at baseline. We compared each T&P construct score between patients who achieved remission and those who did not achieve remission after 6 months of treatment for depression using both subjective and objective measures. All 51 (100%) patients received the 6-month follow-up assessment. Results This study demonstrated that higher scores on T&P personal reserve predicted poorer treatment outcome in patients with MDD. Higher levels of personal reserve, rejection sensitivity, and self-criticism correlated with higher levels of depression. Higher levels of rejection sensitivity and self-criticism were associated with non-remitters; however, when we controlled for baseline depression severity, this relationship did not show significance. Conclusion Although the results are preliminary, this study suggests that high scores on T&P personal reserve predict poorer treatment outcome and T&P rejection sensitivity and self-criticism correlate with the severity of depression. Longer follow-up studies with large sample sizes are required to improve the understanding of these

  20. Transcranial direct current stimulation in a patient with therapy-resistant major depression.

    PubMed

    Palm, Ulrich; Keeser, Daniel; Schiller, Christina; Fintescu, Zoe; Reisinger, Eva; Baghai, Thomas C; Mulert, Christoph; Padberg, Frank

    2009-01-01

    Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been reported to exert significant antidepressant effects in patients with major depression. Several recent studies found an improvement of depressive symptoms in drug-free patients. Here we report the case of a 66-year-old female patient suffering from recurrent major depressive episodes who underwent anodal tDCS of the left dorsolateral PFC over 4 weeks as an add-on treatment to a stable antidepressant medication. Only a modest improvement of depressive symptoms was observed after tDCS, i.e. reduction of the baseline scores in the Hamilton Depression Rating Scale from 23 to 19 and in the Beck Depression Inventory from 27 to 20. However, there was an increase from 52 to 90% in the Regensburg Verbal Fluency Test. In addition, EEG was used to assess the acute effects of tDCS. Low resolution brain electromagnetic tomography (LORETA) showed a left unilateral focal effect (25-40% reduced power) in the delta, theta and alpha frequency bands. The same effect appeared in the surface analysis of the EEG. The absolute, as well as the relative power decreased significantly in the delta, theta and alpha bands after a comparison of the spectral analysis. Though tDCS over 4 weeks did not exert clinically meaningful antidepressant effects in this case of therapy-resistant depression, the findings for cognitive measures and EEG suggest that beneficial effects may occur in depressed subjects and future studies need to further explore this approach also in therapy-resistant major depression.

  1. Mindfulness predicts relapse/recurrence in major depressive disorder after mindfulness-based cognitive therapy.

    PubMed

    Michalak, Johannes; Heidenreich, Thomas; Meibert, Petra; Schulte, Dietmar

    2008-08-01

    Empirical evidence for the effectiveness of mindfulness-based cognitive therapy (MBCT) is encouraging. However, data concerning the role of mindfulness in its relapse preventive effect are lacking. In our study, 25 formerly depressed patients received MBCT. Mindfulness was assessed before and immediately after MBCT using the Mindful Attention and Awareness Scale. Mindfulness significantly increased during MBCT, and posttreatment levels of mindfulness predicted the risk of relapse/recurrence to major depressive disorder in the 12-month follow-up period. Mindfulness predicted the risk of relapse/recurrence after controlling for numbers of previous episodes and residual depressive symptoms. The results provide preliminary evidence for the notion that mindfulness is an important factor in relapse prevention in major depression.

  2. Milnacipran in panic disorder with agoraphobia and major depressive disorder: a case report.

    PubMed

    Chen, Mu-Hong; Liou, Ying-Jay

    2011-01-01

    A 51-year-old woman had panic disorder with agoraphobia and major depressive disorder sequentially. The aforementioned symptoms subsided significantly after treatment with milnacipran, 125 mg, administered daily for 2 months. However, panic attacks with agoraphobia were noted frequently when she tapered down milnacipran to 50 mg daily. She consequently experienced depression that gradually increased in degree, with poor energy, poor sleep, thoughts of helplessness, and ideas of death. After administration of a daily dose of 125 mg of milnacipran for 1 month, her panic attacks with agoraphobia and depressed mood were again alleviated. The present report shows significant effects of milnacipran on the comorbidity of panic disorder with agoraphobia and major depressive disorder.

  3. [Major depression in primary care and clinical impacts of treatment strategies: a literature review].

    PubMed

    Beaucage, Clément; Cardinal, Lise; Kavanagh, Mélanie; Aubé, Denise

    2009-01-01

    Major or clinical depression represents a frequent mental illness that is often associated with a high level of morbidity and mortality. Yet, major depression remains under-diagnosed and under-treated. On the level of treatment, it would appear desirable for reasons of better prognosis, to aim more than the simple reduction of depressive symptoms and target their remission resolutely and the fastest return to the individual's optimal functioning. This article presents a systematic review of the literature relating to the clinical impacts of treatment strategies aiming at the improvement of services offered to people who suffer of clinical depression and who consult in primary care. The authors summarize results drawn from 41 studies that include a measurement of the clinical impacts (reduction of symptoms, response, remission and functioning) of various treatment strategies. It appears that using complex treatment strategies favour positive outcomes. The authors propose various paths of research to further increase current knowledge.

  4. Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

    PubMed Central

    Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

    2015-01-01

    Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

  5. Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression.

    PubMed

    Fischer, Anja; Otte, Christian; Krieger, Thorsten; Nicholls, Robert A; Krüger, Schulamith; Ziegler, Kristin J; Schulz, Karl-Heinz; Heesen, Christoph; Gold, Stefan M

    2012-10-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both receptors are also expressed in lymphocytes, but their role for 'escape' of the immune system from endocrine control is unknown. Using steroid sensitivity of T cell function as a read-out system, we here investigate a potential role of mineralocorticoid receptor (MR) versus glucocorticoid receptor (GR) regulation in the immune system as a biological mechanism underlying MS-associated major depression. Twelve female MS patients meeting diagnostic criteria for current major depressive disorder (MDD) were compared to twelve carefully matched MS patients without depression. We performed lymphocyte phenotyping by flow cytometry. In addition, steroid sensitivity of T cell proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells from depressed MS patients. Experiments with agonists suggested disturbed MR regulation, but intact GR function. Importantly, there were no differences in lymphocyte composition and frequency of T cell subsets, indicating that the differences in steroid sensitivity are unlikely to be secondary to shifts in the immune compartment. To our knowledge, this study provides first evidence for altered steroid sensitivity of T cells from MS patients with comorbid MDD possibly due to MR dysregulation.

  6. Incident major depressive episodes increase the severity and risk of apathy in HIV infection.

    PubMed

    Kamat, Rujvi; Cattie, Jordan E; Marcotte, Thomas D; Woods, Steven Paul; Franklin, Donald R; Corkran, Stephanie H; Ellis, Ronald J; Grant, Igor; Heaton, Robert K

    2015-04-01

    Apathy and depression are inter-related yet separable and prevalent neuropsychiatric disturbances in persons infected with HIV. In the present study of 225 HIV+ persons, we investigated the role of an incident depressive episode in changes in apathy. Participants completed the apathy subscale of the Frontal Systems Behavior Scale during a detailed neuropsychiatric and neuromedical evaluation at visit 1 and again at approximately a 14 month follow-up. The Composite International Diagnostic Interview was used to obtain diagnoses of a new major depressive disorder. At their follow-up visit, participants were classified into four groups depending on their visit 1 elevation in apathy and new major depressive episode (MDE) status. Apathetic participants at baseline with a new MDE (n=23) were at risk for continued, clinically elevated apathy at follow-up, although severity of symptoms did not increase. Of the 144 participants without clinically elevated apathy at visit 1, those who developed a new MDE (n=16) had greater apathy symptomatology at follow-up than those without MDE. These findings suggest that HIV+ individuals, who do not as yet present with elevated apathy, may be at greater risk of elevated psychiatric distress should they experience a new/recurrent depressive episode. Thus, in the context of previous findings, it appears that although apathy and depression are separable constructs, they interact such that a new depressive episode is a risk factor for incident apathy.

  7. The WAIS-III and major depression: absence of VIQ/PIQ differences.

    PubMed

    Gorlyn, Marianne; Keilp, John G; Oquendo, Maria A; Burke, Ainsley K; Sackeim, Harold A; John Mann, J

    2006-10-01

    Poor Performance IQ (PIQ) relative to Verbal IQ (VIQ) is a standard finding in depressed patients administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R). This study examined performance of depressed subjects on the instrument's latest revision, the WAIS-III, which provides a more detailed subdomain profile of intellectual functioning. WAIS-III IQ, index and subscale scores were compared between 121 unmedicated subjects in major depressive episode and 41 healthy volunteers, using demographically adjusted T-score conversions. Depressed subjects had significantly lower PIQ scores, but neither the absolute VIQ/PIQ difference nor prevalence of VIQ/PIQ discrepancies >1 SD differed between groups. Index score differences were exclusively in Processing Speed, and subtest differences only on timed tasks. WAIS-III scores did not differ between subjects with major depressive and bipolar disorders, nor between subjects with and without melancholia or history of suicidal behavior. Results suggest general intellectual performance in depression is best characterized by deficits in processing speed, rather than global nonverbal abilities, and that this deficit is consistent across depression subtypes.

  8. Incident Major Depressive Episodes increase the severity and risk of apathy in HIV infection

    PubMed Central

    Kamat, Rujvi; Cattie, Jordan E.; Marcotte, Thomas D.; Woods, Steven Paul; Franklin, Donald R.; Corkran, Stephanie H.; Ellis, Ronald J.; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy and depression are inter-related yet separable and prevalent neuropsychiatric disturbances in persons infected with HIV. In the present study of 225 HIV+ persons, we investigated the role of an incident depressive episode in changes in apathy. Participants completed the apathy subscale of the Frontal Systems Behavior Scale during a detailed neuropsychiatric and neuromedical evaluation at visit 1 and again at approximately a 14 month follow-up. The Composite International Diagnostic Interview was used to obtain diagnoses of a new major depressive disorder. At their follow-up visit, participants were classified into four groups depending on their visit 1 elevation in apathy and new major depressive episode (MDE) status. Apathetic participants at baseline with a new MDE (n=23) were at risk for continued, clinically elevated apathy at follow-up, although severity of symptoms did not increase. Of the 144 participants without clinically elevated apathy at visit 1, those who developed a new MDE (n=16) had greater apathy symptomatology at follow-up than those without MDE. These findings suggest that HIV+ individuals, who do not as yet present with elevated apathy, may be at greater risk of elevated psychiatric distress should they experience a new/recurrent depressive episode. Thus, in the context of previous findings, it appears that although apathy and depression are separable constructs, they interact such that a new depressive episode is a risk factor for incident apathy. PMID:25679203

  9. Study of the Serum Copper Levels in Patients with Major Depressive Disorder.

    PubMed

    Styczeń, Krzysztof; Sowa-Kućma, Magdalena; Siwek, Marcin; Dudek, Dominika; Reczyński, Witold; Misztak, Paulina; Szewczyk, Bernadeta; Topór-Mądry, Roman; Opoka, Włodzimierz; Nowak, Gabriel

    2016-12-01

    Copper may be involved in the pathophysiology of depression. Clinical data on this issue are very limited and not conclusive. The purpose of the study was to determine the copper concentration in the serum of patients with major depressive disorder and to discuss its potential clinical usefulness as a biomarker of the disease. A case-control clinical study included 69 patients with current depressive episode, 45 patients in remission and 50 healthy volunteers. Cu concentration was measured by electrothermal atomic absorption spectrometry (ETAAS). The mean serum copper level in depressed patients was slightly lower (by 11 %; not statistically significant) than in the control group. Furthermore, there was no significant difference in Cu(2+) concentration between depressive episode and remission, nor between remission and control group. In the remission group were observed significant correlations between copper levels and the average number of relapses over the past years or time of remission. There was no correlation between serum copper and severity of depression, as measured by HDRS and MADRS. The obtained results showed no significant differences between the copper concentration in the blood serum of patients (both with current depressive episode and in remission) and healthy volunteers, as well as the lack of correlations between the copper level in the active stage of the disease and clinical features of the population. Our study is the first conducted on such a large population of patients, so the results may be particularly important and reliable source of knowledge about the potential role of copper in depression.

  10. One-Year Prevalence Rates of Major Depressive Disorder in First-Year University Students

    ERIC Educational Resources Information Center

    Price, E. Lisa; McLeod, Peter J.; Gleich, Stephen S.; Hand, Denise

    2006-01-01

    First-year university students may be more at risk for experiencing Major Depressive Disorder (MDD) than the general population given associated risk factors of this age range. A two-phase procedure was used to estimate the one-year prevalence rate of MDD and comorbid Major Anxiety Disorders among first-year university students at a small Canadian…

  11. "Nudges" to Prevent Behavioral Risk Factors Associated With Major Depressive Disorder.

    PubMed

    Woodend, Ashleigh; Schölmerich, Vera; Denktaş, Semiha

    2015-11-01

    Major depressive disorder-colloquially called "depression"-is a primary global cause of disability. Current preventive interventions, such as problem-solving therapy, are effective but also expensive. "Nudges" are easy and cheap interventions for altering behavior. We have explored how nudging can reduce three behavioral risk factors of depression: low levels of physical activity, inappropriate coping mechanisms, and inadequate maintenance of social ties. These nudges use cognitive biases associated with these behavioral risks, such as valuing the present more than the future, following the herd or the norm, making different choices in light of equivalent conditions, and deciding on the basis of salience or attachment to status quo.

  12. An Examination of Horace Wells' Life as a Manifestation of Major Depressive and Seasonal Affective Disorders.

    PubMed

    Martin, Ramon F; Desai, Sukumar P

    2016-01-01

    Horace Wells was a Hartford, Connecticut, dentist whose practice flourished because of his clinical skills. He had an imaginative mind that propelled him to the forefront in several aspects of dentistry. Unfortunately, he suffered a recurrent "illness" that began in the winter and resolved in the spring. These symptoms were compatible with both major depressive disorder and seasonal affective disorder as a qualifier. Wells' introduction of nitrous oxide as an anesthetic was also associated with self-inhalation. This led to periods of hypomania, followed by depression. With the progression to ether, then chloroform, there was an episode of mania in January 1848, followed by depression and suicide.

  13. Black bile: are elevated monoamines an etiological factor in some cases of major depression?

    PubMed

    Fitzgerald, Paul J

    2013-06-01

    It was hypothesized decades ago that reduced levels of brain monoamines such as serotonin or norepinephrine form, at least in part, a pathophysiological basis for major depression. Consistent with this hypothesis, a conventional strategy used, with varying success, to treat major depression involves administering antidepressant drugs that are thought to boost the synaptic concentration of serotonin and/or norepinephrine. While the reduced monoamine hypothesis is well known but highly controversial and widely considered to be incomplete or simply incorrect, the possibility that elevated monoamines are an etiological factor in some cases of major depression (rather than or in addition to hypomania or mania) has received little attention at all. This paper puts forth the novel hypothesis elevated brain levels of three monoamines - serotonin, norepinephrine, dopamine - are each etiological factors in some cases of major depression. In support of this hypothesis, the paper very briefly reviews relevant data on each of these neurotransmitter systems, including: transporter knockout mice, human genetic association studies, and pharmaceutical studies that enhance or diminish transmitter signaling in either rodents or humans. While all of the published data do not support the hypothesis, there are studies that do for each of the three transmitter systems. The etiological basis of the putative effect of monoamines on depression may be mediated both through genetics and exposure to psychological stress. If the elevated monoamine hypothesis is correct for some persons, pharmaceutical treatment of depression may be significantly improved if the particular elevated monoamine(s) could be identified and then altered on a personalized basis, or perhaps for different putative subtypes of depression. One possibility is that atypical depression involves elevated noradrenergic signaling.

  14. The role of the potassium channel gene KCNK2 in major depressive disorder.

    PubMed

    Congiu, Chiara; Minelli, Alessandra; Bonvicini, Cristian; Bortolomasi, Marco; Sartori, Riccardo; Maj, Carlo; Scassellati, Catia; Maina, Giuseppe; Trabucchi, Luigi; Segala, Matilde; Gennarelli, Massimo

    2015-02-28

    Six single nucleotide polymorphisms (SNPs) of the KCNK2 gene were investigated for their association with major depressive disorder (MDD) and treatment efficacy in 590 MDD patients and 441 controls. The A homozygotes of rs10779646 were significantly more frequent in patients than controls whereas G allele of rs7549184 was associated with the presence of psychotic symptoms and the severity of disease. Evaluating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we confirmed our findings.

  15. Paroxetine Treatment in Children and Adolescents with Major Depressive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Wagner, Karen Dineen; Kutcher, Stan; Krulewicz, Stan; Fong, Regan; Carpenter, David J.; Lipschitz, Alan; Machin, Andrea; Wilkinson, Christel

    2006-01-01

    Objective: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Method: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating…

  16. Theory of mind ability predicts prognosis of outpatients with major depressive disorder.

    PubMed

    Yamada, Kazuo; Inoue, Yumiko; Kanba, Shigenobu

    2015-12-15

    A theory of mind (ToM) deficit in patients with major depressive episodes is associated with difficulty in social adjustment, and thus may indicate a poorer prognosis. We investigated the association between ToM deficits and the outcome in patients who had recovered from major depressive episodes. We evaluated ToM abilities of 100 patients with major depressive disorder during a period of remission. The patients were followed up for one year and their outcomes observed. After one year, patients who had a ToM deficit according to a second-order false belief question relapsed significantly more frequently than did patients who did not have a deficit (Fisher's exact test P<0.0001; relative risk (RR)=8.286; CI 2.608, 26.324). Significant differences between these two groups were shown in scores of the Global Assessment of Functioning Scale (P<0.0001). Our results suggest that a ToM deficit after symptom remission in patients with major depressive disorder predicts a higher relapse rate and lower social function one year after recovering from a major depressive episode.

  17. Diagnostic variability for schizophrenia and major depression in a large public mental health care system dataset.

    PubMed

    Folsom, David P; Lindamer, Laurie; Montross, Lori P; Hawthorne, William; Golshan, Shahrokh; Hough, Richard; Shale, John; Jeste, Dilip V

    2006-11-15

    Administrative datasets can provide information about mental health treatment in real world settings; however, an important limitation in using these datasets is the uncertainty regarding psychiatric diagnosis. To better understand the psychiatric diagnoses, we investigated the diagnostic variability of schizophrenia and major depression in a large public mental health system. Using schizophrenia and major depression as the two comparison diagnoses, we compared the variability of diagnoses assigned to patients with one recorded diagnosis of schizophrenia or major depression. In addition, for both of these diagnoses, the diagnostic variability was compared across seven types of treatment settings. Statistical analyses were conducted using t tests for continuous data and chi-square tests for categorical data. We found that schizophrenia had greater diagnostic variability than major depression (31% vs. 43%). For both schizophrenia and major depression, variability was significantly higher in jail and the emergency psychiatric unit than in inpatient or outpatient settings. These findings demonstrate that the variability of psychiatric diagnoses recorded in the administrative dataset of a large public mental health system varies by diagnosis and by treatment setting. Further research is needed to clarify the relationship between psychiatric diagnosis, diagnostic variability and treatment setting.

  18. Loss of Nfkb1 leads to early onset aging.

    PubMed

    Bernal, Giovanna M; Wahlstrom, Joshua S; Crawley, Clayton D; Cahill, Kirk E; Pytel, Peter; Liang, Hua; Kang, Shijun; Weichselbaum, Ralph R; Yamini, Bakhtiar

    2014-11-01

    NF-κB is a major regulator of age-dependent gene expression and the p50/NF-κB1 subunit is an integral modulator of NF-κB signaling. Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging. Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-κB pathway and mammalian aging.

  19. Family history influences the early onset of hepatocellular carcinoma

    PubMed Central

    Park, Chung-Hwa; Jeong, Seung-Hee; Yim, Hyeon-Woo; Kim, Jin Dong; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    2012-01-01

    AIM: To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients. METHODS: We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records. RESULTS: Of the 2242 patients, 165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diagnosis in the positive- and negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P < 0.0001). Furthermore, among 1713 HCC patients with HBV infection, the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%), whereas those out of 1577 patients with negative family history was 197 (12.5%), suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P = 0.0028). CONCLUSION: More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present. PMID:22690075

  20. Blood-Based Gene Expression Profiles Models for Classification of Subsyndromal Symptomatic Depression and Major Depressive Disorder

    PubMed Central

    Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru

    2012-01-01

    Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell–derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls. PMID:22348066

  1. Blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder.

    PubMed

    Yi, Zhenghui; Li, Zezhi; Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru

    2012-01-01

    Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell-derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls.

  2. Reducing the Burden of Difficult-to-Treat Major Depressive Disorder: Revisiting Monoamine Oxidase Inhibitor Therapy

    PubMed Central

    2013-01-01

    Objective: Difficult-to-treat depression (eg, depression with atypical or anxious symptoms, treatment-resistant depression, or depression with frequent recurrence) is a challenging real-world health issue. This critical review of the literature focuses on monoamine oxidase inhibitor (MAOI) therapy and difficult-to-treat forms of depression. Data Sources: A PubMed literature search was performed in November 2012 and refreshed through January 2013 with no date restrictions using key search terms including MAO inhibitor therapy or MAOI and depression and anxiety, atypical, treatment-resistant, recurrent, relapse, or refractory. Study Selection: Articles were selected to summarize the current needs in difficult-to-treat depression as well as the use of MAOI therapies in this area. Results: Two strategies have fallen out of favor in the care of patients with major depressive disorder. The first is the use of MAOI therapy and the second is the proactive recognition of difficult-to-treat depression that may not respond as well to more frequently used antidepressants. The infrequent use of MAOIs stems from the perception that other oral therapies for depression are safer and easier to use than oral MAOIs; however, transdermal delivery is one potential strategy to improve the safety of this class of agents. Although food-related interactions with transdermal delivery of MAOI therapy can be lessened, clinicians still need to be vigilant for drug-drug interactions and serotonin syndrome. Conclusions: Clinicians should consider MAOIs for patients who have had several unsuccessful trials of antidepressants. Guidelines generally reserve MAOIs as third- and fourth-line treatments due to concerns over safety and tolerability; however, transdermal delivery of an MAOI may allay some of the safety and tolerability concerns. Patients should be provided education about MAOIs and their risks. PMID:24511450

  3. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

    PubMed

    Schlaepfer, Thomas E; Cohen, Michael X; Frick, Caroline; Kosel, Markus; Brodesser, Daniela; Axmacher, Nikolai; Joe, Alexius Young; Kreft, Martina; Lenartz, Doris; Sturm, Volker

    2008-01-01

    Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.

  4. The efficacy of vortioxetine for the treatment of major depressive disorder.

    PubMed

    Dhir, Ashish; Sarvaiya, Jayrajsinh

    2014-12-01

    Vortioxetine (Lu AA21004; Brintellix(®)) has received approval from various international regulatory agencies for the treatment of major depression. The drug molecule has a multimodal mechanism of action that projects it as a unique molecule for the treatment of major depression. These mechanisms include property to inhibit serotonin reuptake via inhibiting serotonin transporters and acting on multiple serotonin receptor subtypes. Vortioxetine is an agonist of 5-HT1A, a partial agonist of 5-HT1B and an antagonist of 5-HT1D, 5-HT3 and 5-HT7 serotoninergic receptors. The molecule has been found to be effective and well-tolerable to be administered in humans for the treatment of major depression. Precautions should be exercised when vortioxetine is prescribed with cytochrome P450 inducers and inhibitors. This review attempts to compile the efficacy profile of vortioxetine in different clinical trials and the results are compared with other standard antidepressants.

  5. Peritraumatic dissociation following motor vehicle accidents: relationship to prior trauma and prior major depression.

    PubMed

    Fullerton, C S; Ursano, R J; Epstein, R S; Crowley, B; Vance, K L; Kao, T C; Baum, A

    2000-05-01

    Individuals who dissociate at the time of a traumatic event (peritraumatic dissociation) are more likely to develop acute and chronic posttraumatic stress disorder (PTSD). However, little is known about who is at risk of peritraumatic dissociation. Motor vehicle accident subjects (N = 122) were systematically recruited and followed over 12 months. We used the Structured Clinical Interview for DSM-III-R (SCID) and the Peritraumatic Dissociative Experiences Questionnaire-Rater Version (PDEQ-RV). Younger subjects were more likely to experience peritraumatic dissociation as were white versus nonwhites, and single versus married subjects. Younger subjects reported a greater number of peritraumatic dissociative symptoms as did subjects with an injured passenger. After adjusting for age and passenger injury, prior major depression was significantly related to more peritraumatic dissociative symptoms. An interaction of age and prior major depression indicated that those who were younger and reported a history of major depression had the greatest number of peritraumatic dissociative symptoms.

  6. Structured regions of α-synuclein fibrils include the early-onset Parkinson’s disease mutation sites

    PubMed Central

    Comellas, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-01-01

    α-Synuclein (AS) fibrils are the major component of Lewy bodies, the pathological hallmark of Parkinson’s disease (PD). Here, we use results from an extensive investigation employing solid-state NMR to present a detailed structural characterization and conformational dynamics quantification of full-length AS fibrils. Our results show that the core extends with a repeated structural motif. This result disagrees with the previously proposed fold of AS fibrils obtained with limited solid-state NMR data. Additionally, our results demonstrate that the three single point mutations associated with early-onset PD—A30P, E46K and A53T—are located in structured regions. We find that E46K and A53T mutations, located in rigid β-strands of the wild-type fibrils, are associated with major and minor structural perturbations, respectively. PMID:21718702

  7. The symptom cluster-based approach to individualize patient-centered treatment for major depression.

    PubMed

    Lin, Steven Y; Stevens, Michael B

    2014-01-01

    Unipolar major depressive disorder is a common, disabling, and costly disease that is the leading cause of ill health, early death, and suicide in the United States. Primary care doctors, in particular family physicians, are the first responders in this silent epidemic. Although more than a dozen different antidepressants in 7 distinct classes are widely used to treat depression in primary care, there is no evidence that one drug is superior to another. Comparative effectiveness studies have produced mixed results, and no specialty organization has published recommendations on how to choose antidepressants in a rational, evidence-based manner. In this article we present the theory and evidence for an individualized, patient-centered treatment model for major depression designed around a targeted symptom cluster-based approach to antidepressant selection. When using this model for healthy adults with major depressive disorder, the choice of antidepressants should be guided by the presence of 1 of 4 common symptom clusters: anxiety, fatigue, insomnia, and pain. This model was built to foster future research, provide a logical framework for teaching residents how to select antidepressants, and equip primary care doctors with a structured treatment strategy to deliver optimal patient-centered care in the management of a debilitating disease: major depressive disorder.

  8. Proton magnetic resonance spectroscopy of late-life major depressive disorder.

    PubMed

    Chen, Cheng-Sheng; Chiang, I-Chan; Li, Chun-Wei; Lin, Wei-Chen; Lu, Chia-Ying; Hsieh, Tsyh-Jyi; Liu, Gin-Chung; Lin, Hsiu-Fen; Kuo, Yu-Ting

    2009-06-30

    The primary goal of this study was to examine the biochemical abnormalities of late-life major depression by using 3-tesla (3-T) proton magnetic resonance spectroscopy ((1)H-MRS). The antidepressant effects on the biochemical abnormalities were investigated as well. Study participants were 27 elderly patients with major depressive disorders (among which 9 were on antidepressant medication) and 19 comparison elderly subjects. (1)H-MRS spectra were acquired from voxels that were placed in the left frontal white matter, left periventricular white matter, and left basal ganglia. Ratios of N-acetylaspartate (NAA), choline (Cho) and myo-inositol to creatine were calculated. Patients with late-life major depressive disorder had a significantly lower NAA/creatine ratio in the left frontal white matter, and higher Cho/creatine and myo-inositol/creatine ratios in the left basal ganglia when compared with the control subjects. The myo-inositol correlated with global cognitive function among the patients. The biochemical abnormalities in late-life major depressive disorder were found on the left side of the frontal white matter and the basal ganglia. Neuron degeneration in the frontal white matter and second messenger system dysfunction or glial dysfunction in the basal ganglia are suggested to be associated with late-life depression.

  9. Prevalence and Factors Associated with Undernutrition among Adults with Major Depressive Disorder in Northwest Ethiopia

    PubMed Central

    Gezahegn, Edmialem; Edris, Melkie

    2016-01-01

    Background. Undernutrition and major depressive disorder are frequently co-occurring. Patients with impaired mental health are strongly vulnerable to the risks of having involuntary weight loss or deficiency of essential nutrients. However, there is no study which assesses undernutrition among major depressive patients in Ethiopia. Method. A total of 422 clients were included in the study. Structured questionnaires and anthropometric measurements were used for collecting the data. Bivariate and multivariate logistic regression model was fitted to identify factors associated with undernutrition. Odds ratio with 95% confidence interval was computed to determine the level of significance. Results. The prevalence of undernutrition was 31.4% [95% CI: 27.2–36.0]. Being in a rural residence [AOR = 1.84, 95% CI (1.18–2.85)], taking multiple medication [AOR = 1.77, 95% CI (1.03–3.05)], taking prescribed diet [AOR = 1.90, 95% CI (1.06–3.41)], and current use of alcohol [AOR = 2.96, 95% CI (1.34–6.55)] were factors significantly associated with undernutrition among depressive patients. Conclusion. The prevalence of undernutrition among adults with major depressive disorder was found to be higher than the general population. Appropriate nutritional education and nutritional assessment are recommended during the course of major depressive disorder. PMID:27990420

  10. The Major Depressive Disorder Hierarchy: Rasch Analysis of 6 items of the Hamilton Depression Scale Covering the Continuum of Depressive Syndrome

    PubMed Central

    2017-01-01

    Objectives Melancholic features of depression (MFD) seem to be a unidimensional group of signs and symptoms. However, little importance has been given to the evaluation of what features are related to a more severe disorder. That is, what are the MFD that appear only in the most depressed patients. We aim to demonstrate how each MFD is related to the severity of the major depressive disorder. Methods We evaluated both the Hamilton depression rating scale (HDRS-17) and its 6-item melancholic subscale (HAM-D6) in 291 depressed inpatients using Rasch analysis, which computes the severity of each MFD. Overall measures of model fit were mean (±SD) of items and persons residual = 0 (±1); low χ2 value; p>0.01. Results For the HDRS-17 model fit, mean (±SD) of item residuals = 0.35 (±1.4); mean (±SD) of person residuals = -0.15 (±1.09); χ2 = 309.74; p<0.00001. For the HAM-D6 model fit, mean (±SD) of item residuals = 0.5 (±0.86); mean (±SD) of person residuals = 0.15 (±0.91); χ2 = 56.13; p = 0.196. MFD ordered by crescent severity were depressed mood, work and activities, somatic symptoms, psychic anxiety, guilt feelings, and psychomotor retardation. Conclusions Depressed mood is less severe, while guilt feelings and psychomotor retardation are more severe MFD in a psychiatric hospitalization. Understanding depression as a continuum of symptoms can improve the understanding of the disorder and may improve its perspective of treatment. PMID:28114341

  11. Major paternal depression and child consultation for developmental and behavioural problems

    PubMed Central

    Davé, Shreya; Sherr, Lorraine; Senior, Rob; Nazareth, Irwin

    2009-01-01

    Background It is well established that maternal depression is associated with enhanced child consultation for developmental and behaviour problems, but there is a dearth of research on paternal depression and child outcome. Aim To assess the association of major paternal depressed mood and child consultation for developmental and behaviour problems. Design of study Cross-sectional study. Setting General practices in London and Hertfordshire, UK. Method Fathers of children aged 4–6 years were recruited via 13 general practices. A sample of 248 biological father and mother dyads completed measures on depressive syndrome (Patient Health Questionnaire), child consultations with health professionals for developmental and behaviour problems, fathering, couple relationship quality, alcohol misuse, other psychiatric impairment, and sociodemographic factors. Results Eight out of 248 fathers (3%) had a major depressive syndrome. Sixty-five out of 247 (26%) fathers reported they were responsible for taking their child to see the doctor at least half the time compared with mothers. Children of fathers with a major depressive syndrome were almost nine times more likely to have consulted a health professional for speech and language problems (adjusted odds ratio [OR] = 8.67, 95% confidence interval [CI] = 1.99 to 37.67, P = 0.004) and seven times more likely to have consulted for externalising behaviour problems (adjusted OR = 6.98, 95% CI = 1.00 to 48.76, P = 0.05). Conclusion Children of fathers with major depression were more likely to consult for speech and language problems and externalising behaviour problems. A longitudinal study is recommended to identify causal mechanisms. PMID:19275834

  12. The role of the kynurenine pathway in suicidality in adolescent major depressive disorder

    PubMed Central

    Bradley, Kailyn A. L.; Case, Julia A. C.; Khan, Omar; Ricart, Thomas; Hanna, Amira; Alonso, Carmen M.; Gabbay, Vilma

    2015-01-01

    The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder (MDD) in adults and adolescents, most recently in suicidality in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we examined the KP in 20 suicidal depressed adolescents—composed of past attempters and those who expressed active suicidal intent—30 non-suicidal depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3-hydroxyanthranilic acid, and KYN/TRP (index of IDO) were assessed. Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding medicated participants, wherein there was also a significant positive correlation between KYN/TRP and suicidality. Finally, although depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to disease severity, anhedonia, and suicidality, the groups did not differ in KP measures. Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar to acutely suicidal youth and are at increased risk for completion of suicide. PMID:25865484

  13. Melancholic features in inpatients with major depressive disorder associate with differential clinical characteristics and treatment outcomes.

    PubMed

    Lin, Ching-Hua; Huang, Chun-Jen; Liu, Shi-Kai

    2016-04-30

    To determine whether the presence of melancholic features in hospitalized patients with major depressive disorder (MDD) was associated with specific clinical characteristics and treatment outcomes, supporting melancholic depression as a distinct subtype within MDD. 126 acutely ill inpatients with MDD were enrolled in an open, 6-week trial with fixed-dose fluoxetine 20mg daily. Symptom severity was assessed regularly, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-S). Melancholic features were defined according to the DSM-IV criteria. Clinical variables were compared between patients with and without melancholic features. Generalized estimating equations method was used to explore the differences in HAMD-17 and CGI-S scores between the 2 groups over time. Clinical response was defined as having a 50% or greater reduction in HAMD-17 scores. 96 (76.2%) of the 126 patients with at least one post-baseline assessment met the criteria for melancholic depression. Melancholic depression differed from non-melancholic depression in clinical characteristics and predicted a better response to fluoxetine treatment. The differentiation between melancholic and non-melancholic depression within MDD hence is clinically significant and valid.

  14. Evening salivary alpha-amylase, major depressive disorder, and antidepressant use in the Netherlands Study of Depression and Anxiety (NESDA).

    PubMed

    Veen, Gerthe; Giltay, Erik J; Licht, Carmilla M M; Vreeburg, Sophie A; Cobbaert, Christa M; Penninx, Brenda W J H; Zitman, Frans G

    2013-06-30

    Salivary alpha-amylase (sAA) may be a suitable index for sympathetic activity and dysregulation of the autonomic nervous system. The relationship between antidepressants and depression with sAA levels was studied, since antidepressants were previously shown to have a profound impact on heart rate variability as an ANS indicator. Data are from 1692 participants of the Netherlands Study of Depression and Anxiety (NESDA) who were recruited from the community, general practice, and specialized mental health care. Differences in evening sAA levels were examined between patient groups (i.e., 752 current major depressive disorder [MDD], 611 remitted MDD, and 329 healthy controls) and between 46 tricyclic antidepressant (TCA) users, 307 selective serotonin reuptake inhibitor (SSRI) users, 97 users of another antidepressant, and 1242 non-users. Each participant sampled twice at 22.00h and 23.00h. In multivariable analysis, there was a trend over the three groups with increasing sAA levels from controls to remitted MDD to current MDD that approached significance. Furthermore, in comparison to non-users of antidepressants, TCA rather than SSRI users showed higher sAA levels, that persisted after multivariable adjustment. The present study shows that higher evening sAA levels in depressed patients, indicative of an increased sympathetic activity, may be induced by TCAs.

  15. Genome-wide Linkage on Chromosome 10q26 for a Dimensional Scale of Major Depression

    PubMed Central

    Knowles, Emma. E. M.; Kent, Jack W.; McKay, D. Reese; Sprooten, Emma; Mathias, Samuel R.; Curran, Joanne E.; Carless, Melanie A.; de Almeida, Marcio A. A.; Goring, Harald, H. H.; Dyer, Tom D.; Olvera, Rene L.; Fox, Peter T.; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C.

    2015-01-01

    Major depressive disorder (MDD) is a common and potentially life-threatening mood disorder. Identifying genetic markers for depression might provide reliable indicators of depression risk, which would, in turn, substantially improve detection, enabling earlier and more effective treatment. The aim of this study was to identify rare variants for depression, modeled as a continuous trait, using linkage and post-hoc association analysis. The sample comprised 1221 Mexican-American individuals from extended pedigrees. A single dimensional scale of MDD was derived using confirmatory factor analysis applied to all items from the Past Major Depressive Episode section of the Mini-International Neuropsychiatric Interview. Scores on this scale of depression were subjected to linkage analysis followed by QTL region-specific association analysis. Linkage analysis revealed a single genome-wide significant QTL (LOD = 3.43) on 10q26.13, QTL-specific association analysis conducted in the entire sample revealed a suggestive variant within an intron of the gene LHPP (rs11245316, p = 7.8×10-04; LD-adjusted Bonferroni-corrected p = 8.6×10-05). This region of the genome has previously been implicated in the etiology of MDD; the present study extends our understanding of the involvement of this region by highlighting a putative gene of interest (LHPP). PMID:26655122

  16. Delivering happiness: translating positive psychology intervention research for treating major and minor depressive disorders.

    PubMed

    Layous, Kristin; Chancellor, Joseph; Lyubomirsky, Sonja; Wang, Lihong; Doraiswamy, P Murali

    2011-08-01

    Despite the availability of many treatment options, depressive disorders remain a global public health problem. Even in affluent nations, 70% of reported cases either do not receive the recommended level of treatment or do not get treated at all, and this percentage does not reflect cases of depression that go unreported due to lack of access to health care, stigma, or other reasons. In developing countries, the World Health Organization estimates that <10% receive proper depression care due to poverty, stigma, and lack of governmental mental health resources and providers. Current treatments do not work for everyone, and even people who achieve remission face a high risk of recurrence and residual disability. The development of low-cost effective interventions that can serve either as initial therapy for mild symptoms or as adjunctive therapy for partial responders to medication is an immense unmet need. Positive activity interventions (PAIs) teach individuals ways to increase their positive thinking, positive affect, and positive behaviors. The majority of such interventions, which have obtained medium-size effect sizes, have been conducted with nondepressed individuals, but two randomized controlled studies in patients with mild clinical depression have reported promising initial findings. In this article, the authors review the relevant literature on the effectiveness of various types of PAIs, draw on social psychology, affective neuroscience and psychophamacology research to propose neural models for how PAIs might relieve depression, and discuss the steps needed to translate the potential promise of PAIs as clinical treatments for individuals with major and minor depressive disorders.

  17. Food for thought: understanding the value, variety and usage of management algorithms for major depressive disorder.

    PubMed

    Katzman, Martin A; Anand, Leena; Furtado, Melissa; Chokka, Pratap

    2014-12-01

    By 2020, depression is projected to be among the most important contributors to the global burden of disease. A plethora of data confirms that despite the availability of effective therapies, major depressive disorder continues to exact an enormous toll; this, in part, is due to difficulties reaching complete remission, as well as the specific associated costs of both the disorder's morbidity and mortality. The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. The use of management algorithms has been shown to improve treatment outcomes in major depressive disorder and may be less costly than "usual care" practices. Nevertheless, many patients with depression remain untreated. As well, even those who are treated often continue to experience suboptimal quality of life. As such, the treatment algorithms in this article may improve outcomes for patients suffering with depression. This paper introduces some of the principal reasons underlying these treatment gaps and examines measures or recommendations that might be changed or strengthened in future practice guidelines to bridge them.

  18. Sibling sex ratio and birth order in early-onset gender dysphoric adolescents.

    PubMed

    Schagen, Sebastian E E; Delemarre-van de Waal, Henriette A; Blanchard, Ray; Cohen-Kettenis, Peggy T

    2012-06-01

    Several sibship-related variables have been studied extensively in sexual orientation research, especially in men. Sibling sex ratio refers to the ratio of brothers to sisters in the aggregate sibships of a group of probands. Birth order refers to the probands' position (e.g., first-born, middle-born, last-born) within their sibships. Fraternal birth order refers to their position among male siblings only. Such research was extended in this study to a large group of early-onset gender dysphoric adolescents. The probands comprised 94 male-to-female and 95 female-to-male gender dysphoric adolescents. The overwhelming majority of these were homosexual or probably prehomosexual. The control group consisted of 875 boys and 914 girls from the TRAILS study. The sibling sex ratio of the gender dysphoric boys was very high (241 brothers per 100 sisters) compared with the expected ratio (106:100). The excess of brothers was more extreme among the probands' older siblings (300:100) than among their younger siblings (195:100). Between-groups comparisons showed that the gender dysphoric boys had significantly more older brothers, and significantly fewer older sisters and younger sisters, than did the control boys. In contrast, the only notable finding for the female groups was that the gender dysphoric girls had significantly fewer total siblings than did the control girls. The results for the male probands were consistent with prior speculations that a high fraternal birth order (i.e., an excess of older brothers) is found in all homosexual male groups, but an elevated sibling sex ratio (usually caused by an additional, smaller excess of younger brothers) is characteristic of gender dysphoric homosexual males. The mechanisms underlying these phenomena remain unknown.

  19. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

    PubMed Central

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. Conclusion This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and

  20. The validity of major depression with atypical features based on a community study.

    PubMed

    Horwath, E; Johnson, J; Weissman, M M; Hornig, C D

    1992-10-01

    This article reports on evidence for the validity of major depression (MDD) with atypical features (defined as overeating and oversleeping) as a distinct subtype based on cross-sectional and 1-year prospective data from the Epidemiologic Catchment Area study. MDD with atypical features, when compared to MDD without atypical features, was associated with a younger age of onset, more psychomotor slowing, and more comorbid panic disorder, drug abuse or dependence, and somatization disorder. These differences could not be explained by differences in demographic characteristics or by symptom severity. This study, based on a community sample, found that major depression with atypical features may constitute a distinct subtype.

  1. Three sisters with very-late-onset major depression and parkinsonism.

    PubMed

    Sechi, GianPietro; Antonio Cocco, Giovanni; Errigo, Alessandra; Deiana, Luca; Rosati, Giulio; Agnetti, Virgilio; Stephen Paulus, Kay; Mario Pes, Giovanni

    2007-03-01

    Familiar Parkinson's disease has an age of onset from the second to the sixth decade, whereas Wilson's disease (WD) usually presents in the first decade of life. We studied three sisters with a form of very-late-onset major depression and parkinsonism with probable linkage to ATP7B gene. Molecular studies demonstrated a nucleotide deletion at the 5'UTR region in a single allele of ATP7B gene. They did not have a family history of WD, or markers indicative for copper deposition in peripheral tissues. We suggest that single allele mutations of ATP7B gene may confer a susceptibility for late-onset major depression and parkinsonism.

  2. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

    ERIC Educational Resources Information Center

    Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

    2007-01-01

    Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

  3. Impulsivity in Juvenile Delinquency: Differences among Early-Onset, Late-Onset, and Non-Offenders

    ERIC Educational Resources Information Center

    Carroll, Annemaree; Hemingway, Francene; Bower, Julie; Ashman, Adrian; Houghton, Stephen; Durkin, Kevin

    2006-01-01

    The present research investigated differences in levels of impulsivity among early-onset, late-onset, and non-offending adolescents. 129 adolescents (114 males, 15 females), of whom 86 were institutionalised (M age = 15.52 years) and 43 were regular school students (M age = 15.40 years) participated. Each participant completed the Adapted…

  4. Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

    ERIC Educational Resources Information Center

    Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

    2010-01-01

    Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

  5. Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

    ERIC Educational Resources Information Center

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

    2012-01-01

    Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated…

  6. Predictors of Early-Onset Permanent Hearing Loss in Malnourished Infants in Sub-Saharan Africa

    ERIC Educational Resources Information Center

    Olusanya, Bolajoko O.

    2011-01-01

    The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the…

  7. Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

    ERIC Educational Resources Information Center

    Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

    2011-01-01

    Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

  8. 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,…

  9. Psychosocial Interventions for Children with Early-Onset Bipolar Spectrum Disorder

    ERIC Educational Resources Information Center

    Lofthouse, Nicholas; Fristad, Mary A.

    2004-01-01

    Once considered virtually nonexistent, bipolar disorder in children has recently received a great deal of attention from mental health professionals and the general public. This paper provides a current review of literature pertaining to the psychosocial treatment of children with early-onset bipolar spectrum disorder (EOBPSD). Commencing with…

  10. Early Onset Ageing and Service Preparation in People with Intellectual Disabilities: Institutional Managers' Perspective

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Wu, Chia-Ling; Lin, Pei-Ying; Lin, Lan-Ping; Chu, Cordia M.

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this…

  11. 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),…

  12. Assessing early-onset hallucinations in the touch-screen generation.

    PubMed

    Demeulemeester, Morgane; Kochman, Fréderic; Fligans, Benjamin; Tabet, Ahmed J; Thomas, Pierre; Jardri, Renaud

    2015-03-01

    The increasing development of apps for digital devices provides an opportunity for new instruments to assess hallucinations in young individuals. Here we present the Multisensory HAllucinations Scale for Children (MHASC), dedicated to assessing complex early-onset hallucinations. The MHASC will soon be translated into multilanguage versions with the support of the International Consortium of Hallucination Research.

  13. The Effects of Childhood ADHD Symptoms on Early-Onset Substance Use: A Swedish Twin Study

    ERIC Educational Resources Information Center

    Chang, Zheng; Lichtenstein, Paul; Larsson, Henrik

    2012-01-01

    Research has documented that children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of substance use problems. Few studies, however, have focused on early-onset substance use. This study therefore investigated how the two symptom dimensions of ADHD (hyperactivity/impulsivity and inattention) are…

  14. White Matter Abnormalities in Early-Onset Schizophrenia: A Voxel-Based Diffusion Tensor Imaging Study

    ERIC Educational Resources Information Center

    Kumra, Sanjiv; Ashtari, Manzar; Cervellione, Kelly L.; Henderson, Inika; Kester, Hana; Roofeh, David; Wu, Jinghui; Clarke, Tana; Thaden, Emily; Kane, John M.; Rhinewine, Joseph; Lencz, Todd; Diamond, Alan; Ardekani, Babak A.; Szeszko, Philip R.

    2005-01-01

    Objective: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). Method: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and…

  15. Pharmacogenetics of antidepressive drugs: a way towards personalized treatment of major depressive disorder.

    PubMed

    Weizman, Shira; Gonda, Xenia; Dome, Peter; Faludi, Gabor

    2012-06-01

    Major depressive disorder is one of the most prevalent psychiatric disorders, and in spite of extensive ongoing research, we neither fully understand its etiopathological background, nor do we possess sufficient pharmacotherapeutic tools to provide remission for all patients. Depression is a heterogenous phenomenon both in its manifestation and its biochemical and genetic background with multiple systems involved. Similarly, the employed pharmaceutical agents in the treatment of depression also effect multiple neurotransmitter systems in the brain. However, we do not yet possess sufficient tools to be able to choose the medication that treats the symptoms most effectively while contributing to minimal side effects in parallel and thus provide personalized pharmacotherapy for depression. In the present paper we review genetic polymorphisms that may be involved in the therapeutic effects and side effects of antidepressive medications and which, in the future, may guide customized selection of the pharmacotherapeutic regimen in case of each patient.

  16. Biomarker approaches in major depressive disorder evaluated in the context of current hypotheses.

    PubMed

    Jentsch, Mike C; Van Buel, Erin M; Bosker, Fokko J; Gladkevich, Anatoliy V; Klein, Hans C; Oude Voshaar, Richard C; Ruhé, Eric G; Eisel, Uli L M; Schoevers, Robert A

    2015-01-01

    Major depressive disorder is a heterogeneous disorder, mostly diagnosed on the basis of symptomatic criteria alone. It would be of great help when specific biomarkers for various subtypes and symptom clusters of depression become available to assist in diagnosis and subtyping of depression, and to enable monitoring and prognosis of treatment response. However, currently known biomarkers do not reach sufficient sensitivity and specificity, and often the relation to underlying pathophysiology is unclear. In this review, we evaluate various biomarker approaches in terms of scientific merit and clinical applicability. Finally, we discuss how combined biomarker approaches in both preclinical and clinical studies can help to make the connection between the clinical manifestations of depression and the underlying pathophysiology.

  17. Selective serotonin reuptake inhibitors for children and adolescents with major depression: current controversies and recommendations.

    PubMed

    Hamrin, Vanya; Scahill, Lawrence

    2005-05-01

    Recent warnings about potential serious adverse effects with the selective serotonin reuptake inhibitors in children and adolescents with depression raises questions about the risk-benefit ratio of these drugs in this population. Published safety and efficacy trials of SSRIs for the treatment of youth with depression are critically reviewed. These data were augmented by information from regulatory hearings in 2003-2004 and selected open-label reports. Based on this review, recommendations for medication treatment and monitoring of children and adolescents with major depression on SSRIs are provided. Emerging data from several clinical trials show that the SSRIs provide moderate benefits for youth with depression. In addition, SSRI treatment may be associated with increased risk of behavioral activation, self-harm, and suicidal ideation. Appropriate use of the SSRIs in children and adolescents requires careful diagnostic assessment, evaluation of comorbidity, and close monitoring, especially early in treatment.

  18. Social support resources and post-acute recovery for older adults with major depression.

    PubMed

    Li, Hong; Morrow-Howell, Nancy; Proctor, Enola; Rubin, Eugene

    2013-08-01

    This study assessed the relationships between older patients' social support resources and depressive symptoms and psychosocial functioning at 6 months following a psychiatric hospital discharge. The data used in this study were extracted from a prospective study titled "Service Use of Depressed Elders after Acute Care" (National Institute of Mental Health-56208). This sample included 148 older patients who participated in the initial and the 6-month follow-up assessment. Ordinary Least Squares regression (OLS) was used to examine important social support resources in relation to older patients' depressive symptoms and psychosocial functioning. A vast majority of patients were embedded in a social support network that consisted of acquaintances and confidants. Patients' depressive symptoms were related to availability of a confidant and the extent to which they spent time with others. However, patients' psychosocial functioning was not related to social support resources assessed in this study.

  19. Relationship of Suicidal Ideation and Behavior to Attachment Style in Patients with Major Depression

    PubMed Central

    ÖZER, Ürün; YILDIRIM, Ejder Akgün; ERKOÇ, Şahap Nurettin

    2015-01-01

    Introduction The attachment theory aims to understand close relationships in adulthood based on the relationship of a child with the caregiver. Attachment styles are classified as secure, preoccupied, fearful and dismissing, which are the subtypes of insecure attachment style. Insecure attachment is suggested to be related to depression and suicide. In this study, the relationship of suicidal ideation and behavior to attachment style is investigated in patients diagnosed with major depression. Methods Sixty-two patients diagnosed with major depressive disorder according to the DSM-IV-TR criteria were taken and divided into two groups, 31 patients with and 31 patients without a past suicide attempt. Sixty healthy volunteers matched with the patients for age, gender and education and comprised the control group. Sociodemographic and clinical data form, Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Hamilton Depression Rating Scale (HDRS), Experiences in Close Relationships Scale (ECR), Scale of Suicidal Ideation and Suicidal Behavior Scale were applied to the groups. Results In the patients with depression, ECR anxiety and avoidance scores were found to be higher compared with those in the control group. There were no differences in the anxiety and avoidance scores between the patients with and without suicide attempt. The rate of participants who showed secure attachment style in the control group was higher than that of those with depression. In the patients with fearful attachment style, the suicide attempt rate was found to be higher than the other groups. A positively significant relationship was detected between ECR anxiety score and scores of HDRS suicide item, Scale of Suicidal Ideation and Suicidal Behavior Scale. Conclusion Patients with depression were more anxious and more avoidant and showed more insecure attachment. In patients with depression with fearful attachment style, suicide attempts were more common.

  20. Season of birth, clinical manifestations and Dexamethasone Suppression Test in unipolar major depression

    PubMed Central

    Fountoulakis, Konstantinos N; Iacovides, Apostolos; Karamouzis, Michael; Kaprinis, George S; Ierodiakonou, Charalambos

    2007-01-01

    Background Reports in the literature suggest that the season of birth might constitute a risk factor for the development of a major psychiatric disorder, possibly because of the effect environmental factors have during the second trimester of gestation. The aim of the current paper was to study the possible relationship of the season of birth and current clinical symptoms in unipolar major depression. Methods The study sample included 45 DSM-IV major depressive patients and 90 matched controls. The SCAN v. 2.0, Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) were used to assess symptomatology, and the 1 mg Dexamethasone Suppression Test (DST) was used to subcategorize patients. Results Depressed patients as a whole did not show differences in birth season from controls. However, those patients born during the spring manifested higher HDRS while those born during the summer manifested the lowest HAS scores. DST non-suppressors were almost exclusively (90%) likely to be born during autumn and winter. No effect from the season of birth was found concerning the current severity of suicidal ideation or attempts. Discussion The current study is the first in this area of research using modern and rigid diagnostic methodology and a biological marker (DST) to categorize patients. Its disadvantages are the lack of data concerning DST in controls and a relatively small size of patient sample. The results confirm the effect of seasonality of birth on patients suffering from specific types of depression. PMID:17683542

  1. Neural correlates of change in major depressive disorder anhedonia following open-label ketamine.

    PubMed

    Lally, Níall; Nugent, Allison C; Luckenbaugh, David A; Niciu, Mark J; Roiser, Jonathan P; Zarate, Carlos A

    2015-05-01

    Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC.

  2. Different risk factor profiles distinguish early-onset from late-onset BKV-replication.

    PubMed

    Schachtner, Thomas; Babel, Nina; Reinke, Petra

    2015-09-01

    Two of three reactivations of latent BKV-infection occur within the first 6 months after renal transplantation. However, a clear differentiation between early-onset and late-onset BKV-replication is lacking. Here, we studied all kidney transplant recipients (KTRs) at our single transplant center between 2004 and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%), among which 24 KTRs (2.8%) showed progression to BKV-associated nephropathy (BKVN). Sixty-seven KTRs with early-onset BKV-replication (65%) and 36 KTRs with late-onset BKV-replication (35%) were identified. A control group of 598 KTRs without BKV-replication was used for comparison. Lymphocyte-depleting induction, CMV-reactivation, and acute rejection increased the risk of early-onset BKV-replication (P < 0.05). Presensitized KTRs undergoing renal retransplantation were those at increased risk of late-onset BKV-replication (P < 0.05). Among KTRs with BK viremia, higher doses of mycophenolate increased the risk of progression to BKVN (P = 0.004). KTRs with progression to BKVN showed inferior allograft function (P < 0.05). KTRs with late-onset BK viremia were more likely not to recover to baseline creatinine after BKV-replication (P = 0.018). Our data suggest different risk factors in the pathogenesis of early-onset and late-onset BKV-reactivation. While a more intensified immunosuppression is associated with early-onset BKV-replication, a chronic inflammatory state in presensitized KTRs may contribute to late-onset BKV-replication.

  3. Early onset neonatal meningitis in Australia and New Zealand, 1992–2002

    PubMed Central

    May, M; Daley, A; Donath, S; Isaacs, D; on, b

    2005-01-01

    Objectives: To study the epidemiology of early onset neonatal bacterial meningitis (EONBM) in Australasia. Design: Prospective surveillance study, 1992–2002, in 20 neonatal units in Australia and New Zealand. EONBM was defined as meningitis occurring within 48 hours of delivery. Results: There were 852 babies with early onset sepsis, of whom 78 (9.2%) had EONBM. The incidence of early onset group B streptococcal meningitis fell significantly from a peak of 0.24/1000 live births in 1993 to 0.03/1000 in 2002 (p trend = 0.002). There was no significant change over time in the incidence of Escherichia coli meningitis. The rate of EONBM in very low birthweight babies was 1.09/1000 compared with the rate in all infants of 0.11/1000. The overall rate of EONBM was 0.41/1000 in 1992 and 0.06 in 2001, but this trend was not significant (p trend = 0.07). Case-fatality rates for EONBM did not change significantly with time. Birth weight <1500 g (odds ratio (OR) 7.2 (95% confidence interval (CI) 4.8 to 10.9)) and Gram negative bacillary meningitis (OR 3.3 (95% CI 2.2 to 4.9)) were significant risk factors for mortality. Sixty two percent of the 129 babies who died from early onset sepsis or suspected sepsis did not have a lumbar puncture performed. Conclusion: The incidence of early onset group B streptococcal meningitis has fallen, probably because of maternal intrapartum antibiotic prophylaxis, without a corresponding change in E coli meningitis. Gram negative bacillary meningitis still carries a worse prognosis than meningitis with a Gram positive organism. PMID:15878934

  4. Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

    PubMed Central

    Nishida, Masaki; Nakashima, Yusaku; Nishikawa, Toru

    2016-01-01

    Introduction Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process. Methods Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants’ brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz) and slow-frequency spindle activity (10.5–12.5 Hz). Result Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups. Conclusion Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep. PMID

  5. Health Related Quality of Life, Depression, Anxiety and Stress in Patients with Beta-Thalassemia Major

    PubMed Central

    Adib-Hajbaghery, M; Ahmadi, M; S, Poormansouri

    2015-01-01

    Background Awareness of factors associated with quality of life (QOL) in patients with beta-Thalassemia major (β-TM) is necessary to develop clinical programs in order to improve social support and QOL in β-TM patients. This study aimed to examine QoL, depression, anxiety, and stress in β-TM patients in Ahvaz, Iran. Materials and Methods A cross-sectional study was conducted on173 β-TM patients aged ≥12 years (12-18=55, ≥19=118). Subjects were selected using a census method. Data collection instrument consisted of three parts including: demographic questions, SF-36 questionnaire and depression, anxiety, and stress scale (DAS-21). Results The participants obtained a mean score of 64.38±18.20 for QOL, 6.4±5.1 for depression, 4.8±3.9 for anxiety, and 7.3±4.9 for stress. Significant relationship was found between QOL and employment (P=0.02) and education level (P<0.001). Patients in the age group of 12-18 years old had higher mean scores in the majority of QoL dimensions than those aged ≤19. The mean scores of depression, anxiety, and stress were higher in patients aged ≤19. No significant correlation was observed between QOL and depression, anxiety, stress scores, and other demographic variables. Moreover, a significant inverse correlation was found between QOL and depression (P<0.001,r= -0.62), anxiety (P<0.001,r= -0.55), and stress scores (P<0.001, r= -0.5) . Conclusion This study showed that β-TM patients experienced a considerable decrease both in their overall QoL and in its dimensions. A majority of the β-TM patients were also suffered from mild to severe depression, anxiety, and stress. PMID:26985352

  6. RELATIONSHIP BETWEEN CARDIAC VAGAL ACTIVITY AND MOOD CONGRUENT MEMORY BIAS IN MAJOR DEPRESSION

    PubMed Central

    Garcia, Ronald G.; Valenza, Gaetano

    2015-01-01

    Background Previous studies suggest that autonomic reactivity during encoding of emotional information could modulate the neural processes mediating mood-congruent memory. In this study, we use a point-process model to determine dynamic autonomic tone in response to negative emotions and its influence on long-term memory of major depressed subjects. Methods Forty-eight patients with major depression and 48 healthy controls were randomly assigned to either neutral or emotionally arousing audiovisual stimuli. An adaptive point-process algorithm was applied to compute instantaneous estimates of the spectral components of heart rate variability [Low frequency (LF), 0.04 to 0.15 Hz; High frequency (HF), 0.15 to 0.4 Hz]. Three days later subjects were submitted to a recall test. Results A significant increase in HF power was observed in depressed subjects in response to the emotionally arousing stimulus (p=0.03). The results of a multivariate analysis revealed that the HF power during the emotional segment of the stimulus was independently associated with the score of the recall test in depressed subjects, after adjusting for age, gender and educational level (Coef. 0.003, 95%CI, 0.0009-0.005, p=0.008). Limitations These results could only be interpreted as responses to elicitation of specific negative emotions, the relationship between HF changes and encoding/recall of positive stimuli should be further examined. Conclusions Alterations on parasympathetic response to emotion are involved in the mood-congruent cognitive bias observed in major depression. These findings are clinically relevant because it could constitute the mechanism by which depressed patients maintain maladaptive patterns of negative information processing that trigger and sustain depressed mood. PMID:26480207

  7. Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder.

    PubMed

    Savitz, Jonathan; Drevets, Wayne C; Wurfel, Brent E; Ford, Bart N; Bellgowan, Patrick S F; Victor, Teresa A; Bodurka, Jerzy; Teague, T Kent; Dantzer, Robert

    2015-05-01

    Low-grade inflammation is characteristic of a subgroup of currently depressed patients with major depressive disorder (dMDD). It may lead to the activation of the kynurenine-metabolic pathway and the increased synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). Nevertheless, few studies have examined whether abnormalities in this pathway are present in remitted patients with MDD (rMDD). Here we compared the serum concentrations of kynurenine metabolites, measured using high performance liquid chromatography with tandem mass spectrometry, across 49 unmedicated subjects meeting DSM-IV-TR criteria for MDD, 21 unmedicated subjects meeting DSM-IV-TR criteria for rMDD, and 58 healthy controls (HCs). There was no significant group difference in the concentrations of the individual kynurenine metabolites, however both the dMDD group and the rMDD group showed a reduction in KynA/QA, compared with the HCs. Further, there was an inverse correlation between KynA/QA and anhedonia in the dMDD group, while in the rMDD group, there was a negative correlation between lifetime number of depressive episodes and KynA/QA as well as a positive correlation between the number of months in remission and KynA/QA. Our results raise the possibility that a persistent abnormality exists within the kynurenine metabolic pathway in MDD that conceivably may worsen with additional depressive episodes. The question of whether persistent abnormalities in kynurenine metabolism predispose to depression and/or relapse in remitted individuals remains unresolved.

  8. Development of a Korean Version of the Perceived Deficits Questionnaire-Depression for Patients with Major Depressive Disorder

    PubMed Central

    Kim, Jae-Min; Hong, Jin-Pyo; Kim, Sang-Dae; Kang, Hee-Ju; Lee, Yong-Sung

    2016-01-01

    Objective Cognitive symptoms are an important component of depression and the Perceived Deficits Questionnaire-Depression is one of only a few instruments available for the subjective assessment of cognitive dysfunction in depression. Thus, the present study aimed to validate a Korean version of the PDQ-D (K-PDQ-D) using patients with major depressive disorder (MDD). Methods This study included 128 MDD patients who were assessed at study entry and 86 of these patients were then completed 12 weeks of antidepressant monotherapy. All subjects were assessed with the K-PDQ-D, the Montgomery-Asberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), the EuroQol-5 dimensions questionnaire (EQ-5D), and the number of sick leave days taken in the previous week. The internal consistency, Guttman’s split-half and test-retest reliabilities, factorial analyses, and concurrent and predictive validities of the K-PDQ-D were investigated. Results The K-PDQ-D exhibited excellent internal consistency and reliabilities, and was composed of four factors with high coefficients of determination. The concurrent validity analyses revealed that the K-PDQ-D scores were significantly correlated with the MADRS, SDS, and EQ-5D scores and the number of sick leave days taken. The K-PDQ-D scores at study entry significantly predicted changes in sick leave days and EQ-5D score from study entry to the 12-week endpoint. Conclusion The newly developed K-PDQ-D is a reliable and valid instrument for the evaluation of subjective cognitive symptoms in MDD patients. The K-PDQ-D may assist in the gathering of unique information regarding subjective cognitive complaints, which is important for the comprehensive evaluation of patients with MDD. PMID:26792037

  9. Does major depressive disorder in parents predict specific fears and phobias in offspring?

    PubMed

    Biel, Matthew G; Klein, Rachel G; Mannuzza, Salvatore; Roizen, Erica R; Truong, Nhan L; Roberson-Nay, Roxann; Pine, Daniel S

    2008-01-01

    Evidence suggests a relationship between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationship between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences.

  10. Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions

    PubMed Central

    Moreno, Carmen; Hasin, Deborah S.; Arango, Celso; Oquendo, Maria A.; Vieta, Eduard; Liu, Shangmin; Grant, Bridget F.; Blanco, Carlos

    2012-01-01

    Objectives To compare the clinical features and course of major depressive episodes (MDE) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Methods Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001–2002), a nationally representative face-to-face survey of more than 43,000 adults in the United States, including 5,695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Results Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent—and number of depressive symptoms per MDE were higher—among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDE, had the worst quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about 10 years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Conclusions Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications. PMID:22548900

  11. ITIH family genes confer risk to schizophrenia and major depressive disorder in the Han Chinese population.

    PubMed

    He, Kuanjun; Wang, Qingzhong; Chen, Jianhua; Li, Tao; Li, Zhiqiang; Li, Wenjin; Wen, Zujia; Qiang, Yu; Wang, Meng; Shen, Jiawei; Song, Zhijian; Ji, Jue; Feng, Guoyin; Qi, Shuguang; Lin, He; Shi, Yongyong; Cheng, Zaohuo

    2014-06-03

    As a major extracellular matrix component, ITIHs played an important role in inflammation and carcinogenesis. Several genome-wide association studies have reported that some positive signals which were derived from the tight linkage disequilibrium region on chromosome 3p21 were associated with both schizophrenia and bipolar disorders in the Caucasian population. To further investigate whether this genomic region is also a susceptibility locus of schizophrenia and major depressive disorder in the Han Chinese population, we conducted this study by recruiting 1235 schizophrenia patients, 1045 major depressive disorder patients and 1235 healthy control subjects in the Han Chinese samples for a case-control study. We genotyped seven SNPs within this region using TaqMan® technology. We found that rs2710322 was significantly associated with schizophrenia (adjusted P(allele) = 0.0018, adjusted P(genotype) = 0.006, OR [95% CI] = 1.278 [1.117-1.462]) while rs1042779 was weakly associated with schizophrenia (adjusted P(allele) = 0.048, OR [95% CI] = 1.164 [1.040-1.303]) and major depressive disorder (adjusted P(allele) = 0.042, OR [95% CI] = 1.178 [1.047-1.326]); it was also our finding that rs3821831 was positively associated with major depressive disorder (adjusted P(allele) = 0.003, adjusted P(genotype) = 0.006, OR [95% CI] = 1.426 [1.156-1.760]). Furthermore, no haplotype was found to be associated with schizophrenia and major depressive disorder. Via the association analysis which combines the schizophrenia and major depressive disorder cases, we also notice that rs1042779 and rs3821831 were significantly associated with combined cases (rs1042779: adjusted P(allele) = 0.012, adjusted P(genotype) = 0.018, OR [95% CI] = 1.171 [1.060-1.292]; rs3821831:adjusted P(genotype) = 0.012, OR [95% CI] = 1.193 [1.010-1.410]). Our results revealed that the shared genetic risk factors of both schizophrenia and major depressive disorder exist in ITIH family genes in the Han Chinese

  12. Brain Serotonin 1A Receptor Binding as a Predictor of Treatment Outcome in Major Depressive Disorder

    PubMed Central

    Miller, Jeffrey M.; Hesselgrave, Natalie; Ogden, R. Todd; Zanderigo, Francesca; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Background We previously reported higher serotonin 1A receptor (5-HT1A) binding in subjects with major depressive disorder (MDD) during a major depressive episode using positron emission tomography imaging with [11C]WAY-100635. 5-HT1A receptor binding is also associated with treatment outcome after nonstandardized antidepressant treatment. We examined whether pretreatment 5-HT1A binding is associated with treatment outcome following standardized escitalopram treatment in MDD. We also compared 5-HT1A binding between all MDD subjects in this cohort and a sample of healthy control subjects. Methods Twenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [11C]WAY-100635, acquiring a metabolite-corrected arterial input function and free-fraction measurement to estimate 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = available receptors and KD = dissociation constant). Major depressive disorder subjects then received 8 weeks of treatment with escitalopram; remission was defined as a posttreatment 24-item Hamilton Depression Rating Scale <10 and ≥50% reduction in Hamilton Depression Rating Scale. Results Remitters to escitalopram had 33% higher baseline 5-HT1A binding in the raphe nuclei than nonremitters (p = .047). Across 12 cortical and subcortical regions, 5-HT1A binding did not differ between remitters and nonremitters (p = .86). Serotonin 1A receptor binding was higher in MDD than control subjects across all regions (p = .0003). Remitters did not differ from nonremitters in several relevant clinical measures. Conclusions Elevated 5-HT1A binding in raphe nuclei is associated with subsequent remission with the selective serotonin reuptake inhibitor escitalopram; this is consistent with data from a separate cohort receiving naturalistic antidepressant treatment. We confirmed our previous findings of higher 5-HT1A binding in current MDD compared with

  13. HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition.

    PubMed

    Keller, J; Gomez, R; Williams, G; Lembke, A; Lazzeroni, L; Murphy, G M; Schatzberg, A F

    2016-08-16

    The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.Molecular Psychiatry advance online publication, 16 August 2016; doi

  14. Long term life dissatisfaction and subsequent major depressive disorder and poor mental health

    PubMed Central

    2011-01-01

    Background Poor mental health, especially due to depression, is one of the main public health problems. Early indicators of poor mental health in general population are needed. This study examined the relationship between long-term life dissatisfaction and subsequent mental health, including major depressive disorder. Method Health questionnaires were sent to a randomly selected population-based sample in 1998 and repeated in 1999 and 2001. In 2005, a clinically studied sub-sample (n = 330) was composed of subjects with (n = 161) or without (n = 169) repeatedly reported adverse mental symptoms at all three previous data collection times. Clinical symptom assessments were performed with several psychometric scales: life satisfaction (LS), depression (HDRS, BDI), hopelessness (HS), mental distress (GHQ), dissociative experiences (DES), and alexithymia (TAS). The long-term life dissatisfaction burden was calculated by summing these life satisfaction scores in 1998, 1999, 2001 and dividing the sum into tertiles. Psychiatric diagnoses were confirmed by SCID-I for DSM-IV in 2005. Logistic regression analyses were performed to assess the studied relationship. Results The previous life dissatisfaction burden associated with adverse socio-demographic, life style and clinical factors. In adjusted logistic regression analyses, it was independently and strongly associated with subsequent major depressive disorder in 2005, even when the concurrent LS score in 2005 was included in the model. Excluding those with reported major depressive disorder in 1999 did not alter this finding. Limitations MDD in 1999 was based on self-reports and not on structured interview and LS data in 2001-2005 was not available. Conclusions The life satisfaction burden is significantly related to major depressive disorder and poor mental health, both in cross-sectional and longitudinal settings. PMID:21861908

  15. VA Health Care: Improvements Needed in Monitoring Antidepressant Use for Major Depressive Disorder and in Increasing Accuracy of Suicide Data

    DTIC Science & T