We read with great interest the recent article by Shin et al. (1). The authors leveraged the substantial Australian Genetics of Depression Study (AGDS) cohort to provide compelling evidence for the clinical and biological validity of the atypical depression subtype. Their integrative analysis of clinical features, polygenic scores (PGSs) for mental, metabolic, and circadian traits, and self-reported treatment outcomes is a significant contribution to the field. The particularly robust finding of an association between a genetic predisposition for eveningness (lower-chronotype PGS) and atypical depression, which persisted after adjustment for body mass index (BMI), is noteworthy and points to a potentially core, BMI-independent pathway.
Comorbidity alters the genetic relationship between anxiety disorders and major depression
The extensive genetic overlap between anxiety disorders (ANX) and major depression (MD) may partly reflect inclusion of comorbid cases in genome-wide association studies (GWAS). We investigated this genetic relationship between ANX and MD with and without mutual comorbidity.
Sex-specific impact of vitamin D and B9 concentrations on neuroticism: a polygenic score-based study
IntroductionNeuroticism is a personality domain with prognostic value for physical and mental health. To properly inform public health policy, it is crucial to uncover the mechanisms underlying high neuroticism. Many internal and external factors that affect brain development and functioning and therefore might contribute to the variability of neuroticism remain understudied. Among them, the impact of vitamin sufficiency is of great interest, as it is a modifiable factor. This study aimed to evaluate the associations of neuroticism with vitamin D (VD) and vitamin B9 (VB9) using polygenic scores (PGS) in a nonclinical cohort.MethodsWe analyzed data from 348 healthy unrelated individuals, including neuroticism scores on the Eysenck Personality Inventory, VD-PGS, VB9-PGS and PGS for neuroticism-related traits.ResultsThe analysis controlling for demographic and genetic confounders revealed a negative association between VB9-PGS and neuroticism scores in women and a positive association between VD-PGS and neuroticism scores in men. The highest values of the VD-PGS were observed in men, who scored high on both neuroticism and extraversion. In men, unlike women, neuroticism scores were not correlated with PGS for neuroticism but were associated with PGS for bipolar disorder type 1 and alcohol use disorders.ConclusionThe results suggest that the effects on neuroticism of genetic propensity for suboptimal vitamin D and B9 concentrations might differ across the two sexes. The findings are consistent with the idea of the importance of vitamin B9 for emotional stability in women and indicate the involvement of genetic factors predisposing to higher vitamin D levels in excitability-related components of neuroticism in men.
Brain Gene Variations Help Explain Neurological and Psychiatric Sex Differences
Thousands of genes are expressed differently in the brains of men and women, researchers have discovered.
The findings could help explain differences in neurodevelopmental, psychiatric, and neurodegenerative disorders between the sexes.
While men are more likely to experience schizophrenia, attention deficit hyperactivity disorder, and Parkinson’s disease, women are more prone to mood disorders and Alzheimer’s disease.
The U.S. study, in Science, is the first systemic single-cell survey of sex differences in gene expression across multiple regions of the human brain.
“Together, these findings provide a comprehensive map of molecular sex differences in the human brain and offer initial insight into their underlying mechanisms and potential functional consequences,” Alex DeCasien, PhD, from the National Institute of Mental Health in Bethesda, Maryland, told Inside Precision Medicine.
DeCasien and co-workers conducted a high-resolution analysis of gene expression in tissue samples from the brains of 15 men and 15 women using single-nucleus RNA sequencing.
They then used data from earlier large neuroimaging studies to select six cortical regions to sample, four of which showed sex-related differences in grey matter volume and two in which no such differences were found.
The team found subtle but widespread differences in gene activity between men and women. Biological sex explained very little of the variance in gene expression across the brain, at less than 1%, but differences were widespread—with more than 3000 genes showing different expression according to sex in at least one cortical region.
The greatest sex-related differences in gene expression were on the sex chromosomes. However, most of the genes showing sex-related variations in expression were autosomal—carried on one of the 22 numbered non-sex chromosomes.
The predominant driver for sex-biased expression of genes on these autosomal chromosomes were sex steroid hormones such as estrogen and testosterone.
Surprisingly, more than half the X chromosome genes in women were expressed in both alleles for at least one cell type. This indicated that many had escaped X chromosome inactivation—a female phenomenon in which one of the two X chromosomes is switched off early in development to stop women producing double the number of X-linked gene products to men.
“That finding has implications for understanding sex-biased disease susceptibility because several genes implicated in neurodevelopmental disorders reside on the X chromosome,” commented Jessica Tollkuhn, PhD, from Cold Spring Harbor Laboratory, and S Marc Breedlove, from Michigan State University, in an accompanying Perspective article.
They noted that autosomal genes showing sex-biased expression were substantially enriched for extracellular matrix components, hormone signaling pathways, and metabolic processes. “Genes with greater expression in women were enriched for mitochondrial and synaptic functions, whereas male-biased genes were associated with metabolic and structural pathways,” the editorialists added.
“By pinpointing these sexually differentiated processes, the data provide a treasure trove for the discovery of biomarkers of and/or therapeutic targets for differential disease risk in men and women.”
DeCasien and team added: “These findings raise the possibility that sex differences in gene expression modulate the magnitude of genetic effects at risk loci, contributing to differences in disease vulnerability and to reduced portability of polygenic risk prediction across sexes.”
The post Brain Gene Variations Help Explain Neurological and Psychiatric Sex Differences appeared first on Inside Precision Medicine.
Can psychiatric genetics advance without incorporating a lifecourse perspective?
Psychiatric disorders unfold over the lifecourse, yet genomic studies of these conditions overwhelmingly rely on phenotypes collected at a single time point, often in adulthood. Genome-wide association studies (GWAS) of psychiatric conditions may therefore miss genetic variants with time-varied relevance to etiology, prevention and treatment, such as those that influence trajectories of symptoms and behaviors, age-at-onset, course of treatment response, and co-evolution of comorbidities. With recent advances in longitudinal biobanks and analytic tools, we posit that incorporating a lifecourse perspective in psychiatric genetics will enable critically relevant insights into each of these areas of investigation.
Gut microbiota profiles in anorexia nervosa: associations with disease severity, BMI, and history of childhood trauma
Study objectivesEmerging evidence suggests a possible link between anorexia nervosa (AN) and alterations in the gut microbiota. This study aimed to characterize the gut microbiota profile in a cohort of Chinese female patients with AN.MethodA comparative analysis of the gut microbiota was conducted between 30 female patients with AN and 30 sex- and age-matched healthy controls (HCs). Fecal samples were collected for 16S rRNA gene sequencing analysis. All participants were assessed using the Eating Disorder Inventory (EDI) and the Childhood Trauma Questionnaire (CTQ). Bioinformatics analysis was performed using QIIME2, and statistical analyses were carried out with SPSS 26.0 and R software. Correlations between microbiota differences and body mass index (BMI), EDI, and CTQ were further investigated.ResultsThe analysis revealed differences in beta diversity and the abundances of specific microbial taxa between the two groups; however, no significant differences were observed in alpha diversity nor in the associations between gut microbiota and BMI, disease severity, or childhood trauma.ConclusionsThis study identified limited differences in the gut microbiota composition between patients with AN and HCs. Critically, no robust associations between gut microbiota and clinical features were found after rigorous multiple comparison correction. While nominal (uncorrected) correlations were observed between the specific microbiota and psychological traits, these results are exploratory and should be considered hypothesis-generating. They highlight a potential avenue for future research but require validation in larger, longitudinal cohorts to determine their reproducibility and biological significance.
Closing the Gap in Autism Genetics: Population-Specific Variants and the Imperative for Global Inclusion
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental condition with an exceptionally complex and heterogeneous genetic architecture, encompassing both polygenic common variants and rare, high-impact variants. Over the past decade, large-scale sequencing studies in Europe and North America have identified hundreds of ASD risk genes and substantially advanced biological insight. However, the global distribution of ASD genomic research remains profoundly imbalanced, with most non-European ancestry populations severely underrepresented.
Understanding Genomics in the Context of ESD
This paragraph serves as an introduction to your blog post. Begin by discussing the primary theme or topic that you plan to cover, ensuring it captures the reader’s interest from the very first sentence. Share a brief overview that highlights why this topic is important and how it can provide value. Use this space to set the tone for the rest of the article, preparing readers for the journey ahead. Keep your language approachable, yet informative, to create a strong connection. Bipolar, ADHA and autism may all sometimes feel dissociated, and our new therapy has been shown in a clinical trial with mushroom extracts to reduce stress and anxiety.