Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Background Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Methods Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Results Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001) Conclusions Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

Pharmacogenomics of Lithium Response in Bipolar Disorder

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

Reduced cortical gyrification in the posteromedial cortex in unaffected relatives of schizophrenia patients with high genetic loading

Although abnormal cortical gyrification has been consistently reported in patients with schizophrenia, whether gyrification abnormalities reflect a genetic risk for the disorder remains unknown. This study investigated differences in cortical gyrification between unaffected relatives (URs) with high genetic loading for schizophrenia and healthy controls (HCs) to identify potential genetic vulnerability markers. A total of 50 URs of schizophrenia patients and 50 matched HCs underwent T1-weighted magnetic resonance imaging to compare whole-brain gyrification using the local gyrification index (lGI). Then, the lGI clusters showing significant differences were compared between the UR subgroups based on the number of first-degree relatives with schizophrenia to identify the effect of genetic loading on cortical gyrification changes. The URs exhibited significantly lower cortical gyrification than the HCs in clusters including medial parieto-occipital and cingulate regions comprising the bilateral precuneus, cuneus, pericalcarine, lingual, isthmus cingulate, and posterior cingulate gyri. Moreover, URs who had two or more first-degree relatives with schizophrenia showed greater gyrification reductions in these clusters than those who had at least one first-degree relative with schizophrenia. Our findings of reduced gyrification in URs, which are consistent with accumulated evidence of hypogyria observed in regions showing patient-control differences in previous studies, highlight that such hypogyria in posteromedial regions may serve as a genetic vulnerability marker and reflect early neurodevelopmental abnormalities resulting from a genetic risk for schizophrenia.

Suicide and genes: Commentary on Hawton and van Heeringen (Lancet 2009; 373: 1372-81)

Hawton’s and van Heeringen’s seminar on suicide is a rich source of current knowledge on the topic and highly useful for generalists. However, genetic risk factors for suicide are underappreciated in the seminar. Although family history of suicide is mentioned as important and genetic loading is listed under distal risk factors, their close connection is not emphasised: familial clustering of suicide is partly due to genetic risk factors. Convergent evidence towards this end has emerged from distinctly different genetically informative research designs. Appropriate consideration of these insights is an important public health agenda and matters for mental health literacy, as international surveys suggest disbelief in the genetics of suicide is widespread among medical and psychology undergraduates and in the general population.

CNVs and Chromosomal Aneuploidy in Patients With Early-Onset Schizophrenia and Bipolar Disorder: Genotype-Phenotype Associations

Introduction: Early-onset schizophrenia (EOS) and bipolar disorder (EOB) start before the age of 18 years and have a more severe clinical course, a worse prognosis, and a greater genetic loading compared to the late-onset forms. Copy number variations (CNVs) are an important genetic factor in the etiology of psychiatric disorders. Therefore, this study aimed to analyze CNVs in patients with EOS and EOB and to establish genotype-phenotype relationships for contiguous gene syndromes or genes affected by identified CNVs.Methods: Molecular karyotyping was performed in 45 patients, 38 with EOS and seven with EOB hospitalized between 2010 and 2017. The exclusion criteria were medical or neurological disorders or IQ under 70. Detected CNVs were analyzed according to the standards and guidelines of the American College of Medical Genetics.Result: Molecular karyotyping showed CNVs in four patients with EOS (encompassing the PAK2, ADAMTS3, and ADAMTSL1 genes, and the 16p11.2 microduplication syndrome) and in two patients with EOB (encompassing the ARHGAP11B and PRODH genes). In one patient with EOB, a chromosomal aneuploidy 47, XYY was found.Discussion: Our study is the first study of CNVs in EOS and EOB patients in Slovenia. Our findings support the association of the PAK2, ARHGAP11B, and PRODH genes with schizophrenia and/or bipolar disorder. To our knowledge, this is also the first report of a multiplication of the ADAMTSL1 gene and the smallest deletion of the PAK2 gene in a patient with EOS, and one of the few reports of the 47, XYY karyotype in a patient with EOB.

Brain function distinguishes female carriers and non-carriers of familial risk for autism

Background Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed (“carrier”) females. Methods Using functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays—depicting biological versus non-biological motion—in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females—i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm. Results We observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies. Limitations We were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position. Conclusions These methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD.

First detection of SARS-CoV-2 genetic material in the vicinity of COVID-19 isolation centre through wastewater surveillance in Bangladesh

In the course of a COVID-19 pandemic, 0.33 million people got infected in Bangladesh, we made the first and successful attempt to detect SARS-CoV-2 viruses' genetic material in the vicinity wastewaters of an isolation centre i.e. Shaheed Bhulu Stadium, situated at Noakhali. The idea was to understand the genetic loading variation, both temporal and distance-wise in the nearby wastewater drains when the number of infected COVID-19 patients is not varying much. Owing to the fact that isolation center, in general, always contained a constant number of 200 COVID-19 patients, the prime objective of the study was to check if several drains carrying RNA of coronavirus are actually getting diluted or accumulated along with the sewage network. Our finding suggested that while the temporal variation of the genetic load decreased in small drains over the span of 50 days, the main sewer exhibited accumulation of SARS-CoV-2 RNA. Other interesting finding displays that probably distance of sampling location in meters is not likely to have a significant impact on gene detection concentration, although the quantity of the RNA extracted in the downstream of the drain was higher. These findings are of immense value from the perspective of wastewater surveillance of COVID-19, as they largely imply that we do not need to monitor every wastewater system, and probably major drains monitoring may illustrate the city health. Perhaps, we are reporting the accumulation of SARS-CoV-2 genetic material along with the sewer network i.e. from primary to tertiary drains. The study sought further data collection in this line to simulate conditions prevailed in the most of south Asian country and to shed further light on the temporal variation and decay/accumulation processes of the genetic load of the SARS-COV-2.