Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain ...disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
To present estimates of the lifetime prevalence of DSM-IV mental disorders with and without severe impairment, their comorbidity across broad classes of disorder, and their sociodemographic ...correlates.
The National Comorbidity Survey-Adolescent Supplement NCS-A is a nationally representative face-to-face survey of 10,123 adolescents aged 13 to 18 years in the continental United States. DSM-IV mental disorders were assessed using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview.
Anxiety disorders were the most common condition (31.9%), followed by behavior disorders (19.1%), mood disorders (14.3%), and substance use disorders (11.4%), with approximately 40% of participants with one class of disorder also meeting criteria for another class of lifetime disorder. The overall prevalence of disorders with severe impairment and/or distress was 22.2% (11.2% with mood disorders, 8.3% with anxiety disorders, and 9.6% behavior disorders). The median age of onset for disorder classes was earliest for anxiety (6 years), followed by 11 years for behavior, 13 years for mood, and 15 years for substance use disorders.
These findings provide the first prevalence data on a broad range of mental disorders in a nationally representative sample of U.S. adolescents. Approximately one in every four to five youth in the U.S. meets criteria for a mental disorder with severe impairment across their lifetime. The likelihood that common mental disorders in adults first emerge in childhood and adolescence highlights the need for a transition from the common focus on treatment of U.S. youth to that of prevention and early intervention.
Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation ...and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.
The question of ‘what is a mental disorder?’ is central to the philosophy of psychiatry, and has crucial practical implications for psychiatric nosology. Rather than approaching the problem in terms ...of abstractions, we review a series of exemplars – real-world examples of problematic cases that emerged during work on and immediately after DSM-5, with the aim of developing practical guidelines for addressing future proposals. We consider cases where (1) there is harm but no clear dysfunction, (2) there is dysfunction but no clear harm, and (3) there is possible dysfunction and/or harm, but this is controversial for various reasons. We found no specific criteria to determine whether future proposals for new entities should be accepted or rejected; any such proposal will need to be assessed on its particular merits, using practical judgment. Nevertheless, several suggestions for the field emerged. First, while harm is useful for defining mental disorder, some proposed entities may require careful consideration of individual v. societal harm, as well as of societal accommodation. Second, while dysfunction is useful for defining mental disorder, the field would benefit from more sharply defined indicators of dysfunction. Third, it would be useful to incorporate evidence of diagnostic validity and clinical utility into the definition of mental disorder, and to further clarify the type and extent of data needed to support such judgments.
To estimate the association of prior lifetime mental disorders with transitions across stages of substance use in a cross-sectional, nationally representative sample of US adolescents.
The sample ...includes 10,123 adolescents aged 13 to 18 years who participated in the National Comorbidity Survey-Adolescent Supplement (NCS-A), and who were directly interviewed with the Composite International Diagnostic Interview (CIDI) Version 3.0 that generates criteria for DSM-IV disorders.
Adolescents with prior lifetime mental disorders had high rates of both alcohol (10.3%) and illicit drug (14.9%) abuse, with or without dependence. Alcohol and drug abuse were highest among adolescents with prior anxiety disorders (17.3% and 20%, respectively) and behavior disorders (15.6% and 24%, respectively). Any prior disorder significantly increased the risk of transition from nonuse to first use, and from use to problematic use of either alcohol or illicit drugs. Multivariate models attenuated the magnitude of the risk of transition associated with each disorder, although prior weekly smoking and illicit drug use demonstrated significant risks of transitions across the 3 stages of alcohol or drug use, as did behavior disorders.
The findings provide the first evidence from a nationally representative sample that prior mental disorders represent risk factors for the transition from nonuse to use, and the progression to drug- and alcohol-related problems. Treatment of primary mental disorders is likely to be an important target for the prevention of secondary substance use disorders in youth.
Rationale
Psychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate this association. A ...number of preclinical studies have investigated the effect of stress on microglial activity. However, these have not been systematically reviewed before.
Objectives
This study aims to systematically review the effects of stress on microglia, as indexed by the histological microglial marker ionised calcium binding adaptor molecule 1 (Iba-1), and consider the implications of these for the role of stress in the development of mental disorders.
Methods
A systematic review was undertaken using pre-defined search criteria on PubMed and EMBASE. Inclusion and data extraction was agreed by two independent researchers after review of abstracts and full text.
Results
Eighteen studies met the inclusion criteria. These used seven different psychosocial stressors, including chronic restraint, social isolation and repeated social defeat in gerbils, mice and/or rats. The hippocampus (11/18 studies) and prefrontal cortex (13/18 studies) were the most frequently studied areas. Within the hippocampus, increased Iba-1 levels of between 20 and 200 % were reported by all 11 studies; however, one study found this to be a duration-dependent effect. Of those examining the prefrontal cortex, ∼75 % found psychosocial stress resulted in elevated Iba-1 activity. Elevations were also consistently seen in the nucleus accumbens, and under some stress conditions in the amygdala and paraventricular nucleus.
Conclusions
There is consistent evidence that a range of psychosocial stressors lead to elevated microglial activity in the hippocampus and good evidence that this is also the case in other brain regions. These effects were seen with early-life/prenatal stress, as well as stressors in adulthood. We consider these findings in terms of the two-hit hypothesis, which proposes that early-life stress primes microglia, leading to a potentiated response to subsequent stress. The implications for understanding the pathoaetiology of mental disorders and the development of new treatments are also considered.
Domestic violence in the perinatal period is associated with adverse obstetric outcomes, but evidence is limited on its association with perinatal mental disorders. We aimed to estimate the ...prevalence and odds of having experienced domestic violence among women with antenatal and postnatal mental disorders (depression and anxiety disorders including post-traumatic stress disorder PTSD, eating disorders, and psychoses).
We conducted a systematic review and meta-analysis (PROSPERO reference CRD42012002048). Data sources included searches of electronic databases (to 15 February 2013), hand searches, citation tracking, update of a review on victimisation and mental disorder, and expert recommendations. Included studies were peer-reviewed experimental or observational studies that reported on women aged 16 y or older, that assessed the prevalence and/or odds of having experienced domestic violence, and that assessed symptoms of perinatal mental disorder using a validated instrument. Two reviewers screened 1,125 full-text papers, extracted data, and independently appraised study quality. Odds ratios were pooled using meta-analysis. Sixty-seven papers were included. Pooled estimates from longitudinal studies suggest a 3-fold increase in the odds of high levels of depressive symptoms in the postnatal period after having experienced partner violence during pregnancy (odds ratio 3.1, 95% CI 2.7-3.6). Increased odds of having experienced domestic violence among women with high levels of depressive, anxiety, and PTSD symptoms in the antenatal and postnatal periods were consistently reported in cross-sectional studies. No studies were identified on eating disorders or puerperal psychosis. Analyses were limited because of study heterogeneity and lack of data on baseline symptoms, preventing clear findings on causal directionality.
High levels of symptoms of perinatal depression, anxiety, and PTSD are significantly associated with having experienced domestic violence. High-quality evidence is now needed on how maternity and mental health services should address domestic violence and improve health outcomes for women and their infants in the perinatal period.
Genetics and genomics of psychiatric disease Geschwind, Daniel H.; Flint, Jonathan
Science (American Association for the Advancement of Science),
09/2015, Letnik:
349, Številka:
6255
Journal Article
Recenzirano
Odprti dostop
Large-scale genomic investigations have just begun to illuminate the molecular genetic contributions to major psychiatric illnesses, ranging from small-effect-size common variants to ...larger-effect-size rare mutations. The findings provide causal anchors from which to understand their neurobiological basis. Although these studies represent enormous success, they highlight major challenges reflected in the heterogeneity and polygenicity of all of these conditions and the difficulty of connecting multiple levels of molecular, cellular, and circuit functions to complex human behavior. Nevertheless, these advances place us on the threshold of a new frontier in the pathophysiological understanding, diagnosis, and treatment of psychiatric disease.
Internet Gaming Disorder in the DSM-5 Petry, Nancy M.; Rehbein, Florian; Ko, Chih-Hung ...
Current psychiatry reports,
09/2015, Letnik:
17, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The fifth revision of the
Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) includes in its research appendix a potential new diagnosis—Internet gaming disorder. This article outlines the ...debate surrounding non-substance addictions and the rationale for including this condition in the “Conditions for Further Study” chapter in DSM-5 Section III. It also describes the diagnostic criteria that DSM-5 recommends and methods to assess Internet gaming disorder. The paper details international research related to prevalence rates, demographic, psychiatric, and neurobiological risk factors, the natural course of the condition, and promising treatment approaches. The paper concludes by describing important issues for research to address prior to official recognition of this condition as a mental disorder.
The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to ...many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.
PDF
