Etiology Of Psychiatric Illness Research Articles

Epigenetic Basis of Psychiatric Disorders: A Narrative Review.

Psychiatric disorders are complex, multifactorial illnesses with a demonstrated biological component in their etiopathogenesis. Epigenetic modifications, through the modulation of DNA methylation, histone modifications and RNA interference, tune tissue-specific gene expression patterns and play a relevant role in the etiology of psychiatric illnesses. This review aims to discuss the epigenetic mechanisms involved in psychiatric disorders, their modulation by environmental factors and their interactions with genetic variants, in order to provide a comprehensive picture of their mutual crosstalk. In accordance with the PRISMA guidelines, systematic searches of Medline, EMBASE, PsycINFO, Web of Science, Scopus, and the Cochrane Library were conducted. Exposure to environmental factors, such as poor socio-economic status, obstetric complications, migration, and early life stressors, may lead to stable changes in gene expression and neural circuit function, playing a role in the risk of psychiatric diseases. The most replicated genes involved by studies using different techniques are discussed. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions and they interact with genetic variants in determining the risk of psychiatric disorders. An increasing amount of evidence suggests that epigenetics plays a pivotal role in the etiopathogenesis of psychiatric disorders. New therapeutic approaches may work by reversing detrimental epigenetic changes that occurred during the lifespan.

M180. SUSCEPTIBILITY AND RESILIENCE IN A MOUSE MODEL OF MATERNAL IMMUNE ACTIVATION

BackgroundEpidemiological studies over the past decades have repeatedly implicated maternal immune activation (MIA) in the etiology of psychiatric illnesses, including schizophrenia and related psychotic disorders. Not all offspring exposed to MIA, however, develop overt pathologies, suggesting that some are susceptible while others are resilient to MIA. To elucidate susceptibility and resilience in MIA, we used a mouse model that is based on prenatal exposure to the viral mimic poly(I:C).MethodsPoly(I:C)-based MIA was induced in C57BL6/N mice on gestation day 12. Control dams received vehicle solution only. Offspring of poly(I:C)- or vehicle-exposed dams were subjected to a comprehensive behavioral testing battery when they reached adulthood (12 weeks of age onwards). Next-generation mRNA sequencing and gene pathway analyses were conducted after behavioral testing to explore the molecular correlates of resilience and susceptibility to MIA.ResultsBehavioral characterization coupled with unbiased TwoStep cluster analysis of a large number offspring (N >150) revealed that offspring exposed to MIA could be stratified into susceptible and resilient subgroups. While the former was characterized by deficits in social interaction, sensorimotor gating, and working memory, the behavioral profile of the latter was indistinguishable from control offspring. Susceptible and resilient MIA offspring were also dissociable by the presence of distinct molecular profiles in cortical and subcortical brain areas. In the medial prefrontal cortex, susceptible MIA offspring displayed a more profound deregulation of genes relevant for oxidative phosphorylation and mitochondrial functions than resilient MIA offspring. In the amygdala, the susceptible and resilient offspring differed in gene transcription pertinent to opioid signaling, DARPP-32 signaling, and G protein-coupled receptor signaling.DiscussionOur data show that MIA can result in substantial phenotypic and transcriptomic variability even in the context of genetic homogeneity and under identical experimental conditions. If extended further, our model system may help to explain why only a subgroup of offspring exposed to MIA develops overt neurodevelopmental sequelae.

Serum epidermal growth factor, clinical illness course, and limbic brain volumes in early-stage bipolar disorder

BackgroundEpidermal growth factor (EGF) belongs to a family of growth factors implicated in the etiology of psychiatric illnesses. We conducted this cross-sectional case-control study to determine whether (1) serum EGF levels differ between bipolar disorder (BD) patients and non-BD comparison subjects, (2) EGF levels in patients are influenced by mood illness related factors (number of past mood episodes, medication treatment) and non-mood illness related factors (body mass index), and (3) lower EGF levels predict lower limbic brain volumes in BD. MethodsWe measured serum EGF in 51 early-stage BD patients and 22 healthy comparison subjects (HS). A subset of 25 patients underwent cerebral magnetic resonance imaging (MRI). Participants were assessed at the University of British Columbia Mood Disorders Centre between June 2004 and June 2012. ResultsA general linear model with diagnosis and BMI category (overweight/obese vs normal weight) as factors showed that patients had lower mean log(e)-transformed EGF (LnEGF) than HS (4.99 vs 5.47, p = .011). There was no effect of BMI and no diagnosis x BMI interaction. Multiple linear regression models showed that in patients, more past mood episodes predicted lower LnEGF (β = −0.358, t = −2.585, p = .013) and lower LnEGF predicted lower bilateral temporal lobe volumes (left: β = 0.560, p = .011; right: β = 0.543, p = .009). LimitationsOur cross-sectional study design limits our ability to make inferences about the causal directions of the relationships between EGF, diagnosis, mood episodes, and brain volumes. ConclusionsThese findings provide preliminary evidence that EGF is a novel biomarker that may play a role in the pathophysiology of BD.

There is increasing evidence to suggest that brain inflammation could play a key role in the aetiology of psychiatric illness. Could inflammation be a cause of the premenstrual syndromes PMS and PMDD?

There is increasing evidence to suggest that brain inflammation could play a key role in the aetiology of psychiatric illness. Could inflammation be a cause of the premenstrual syndromes PMS and PMDD?

Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota-immune-brain axis

Early-life stress is an established risk for the development of psychiatric disorders. Post-weaning isolation rearing of rats produces lasting developmental changes in behavior and brain function that may have translational pathophysiological relevance to alterations seen in schizophrenia, but the underlying mechanisms are unclear. Accumulating evidence supports the premise that gut microbiota influence brain development and function by affecting inflammatory mediators, the hypothalamic–pituitaryadrenal axis and neurotransmission, but there is little knowledge of whether the microbiota-gut-brain axis might contribute to the development of schizophrenia-related behaviors. To this end the effects of social isolation (SI; a well-validated animal model for schizophrenia)-induced changes in rat behavior were correlated with alterations in gut microbiota, hippocampal neurogenesis and brain cytokine levels. Twenty-four male Lister hooded rats were housed in social groups (group-housed, GH, 3 littermates per cage) or alone (SI) from weaning (post-natal day 24) for four weeks before recording open field exploration, locomotor activity/novel object discrimination (NOD), elevated plus maze, conditioned freezing response (CFR) and restraint stress at one week intervals. Post-mortem caecal microbiota composition, cortical and hippocampal cytokines and neurogenesis were correlated to indices of behavioral changes. SI rats were hyperactive in the open field and locomotor activity chambers traveling further than GH controls in the less aversive peripheral zone. While SI rats showed few alterations in plus maze or NOD they froze for significantly less time than GH following conditioning in the CFR paradigm, consistent with impaired associative learning and memory. SI rats had significantly fewer BrdU/NeuN positive cells in the dentate gyrus than GH controls. SI rats had altered microbiota composition with increases in Actinobacteria and decreases in the class Clostridia compared to GH controls. Differences were also noted at genus level. Positive correlations were seen between microbiota, hippocampal IL-6 and IL-10, conditioned freezing and open field exploration. Adverse early-life stress resulting from continuous SI increased several indices of ‘anxiety-like’ behavior and impaired associative learning and memory accompanied by changes to gut microbiota, reduced hippocampal IL-6, IL-10 and neurogenesis. This study suggests that early-life stress may produce long-lasting changes in gut microbiota contributing to development of abnormal neuronal and endocrine function and behavior which could play a pivotal role in the aetiology of psychiatric illness.

Changes in the Psychiatric Landscape

Changes in the Psychiatric Landscape

Highlights of the 1999 Institute on Psychiatric Services

Highlights of the 1999 Institute on Psychiatric Services

Congenital dermatoglyphic malformations in severe bipolar disorder

Dermatoglyphic alterations may be the result of early prenatal disturbances thought to be implicated in the aetiology of psychiatric illness. In order to test this hypothesis in the particular case of bipolar disorder, we assessed two congenital dermatoglyphic malformations (ridge dissociation (RD) and abnormal features (AF)) and two metric dermatoglyphic traits (total finger ridge count (TFRC) and total a-b ridge count (TABRC)) in a sample of 118 patients with chronic DSM-III-R bipolar illness, and 216 healthy controls. Bipolar cases showed a significant excess of RD and AF (OR=2.80; 95% CI: 2.31–3.38) when compared with controls. In the cases, the presence of anomalies was associated with earlier age of onset. No differences were found for TFRC and TABRC. No associations were found with sex or familial morbid risk of psychiatric disorders. Our findings add further weight to the suggestion that early developmental disruption is a risk factor for later bipolar disorder.

Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial

Methylation has been implicated in the etiology of psychiatric illness. Parenteral S-adenosylmethionine, a methyl group donor, has been shown to be an effective antidepressant. The authors studied the antidepressant effect of oral S-adenosylmethionine in a randomized, double-blind, placebo-controlled trial for 15 inpatients with major depression. The results suggest that oral S-adenosylmethionine is a safe, effective antidepressant with few side effects and a rapid onset of action. S-Adenosylmethionine induced mania in a patient with no history of mania. S-Adenosylmethionine may be useful for patients who cannot tolerate tricyclic anti-depressants. These findings support a role for methylation in the pathophysiology of depression.