@article {2364, title = {Analysis of whole exome sequencing in severe mental illness hints at selection of brain development and immune related genes.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 Oct 26}, pages = {21088}, abstract = {

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 74 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimer{\textquoteright}s disease and cognitive abilities in genome wide association studies. We then checked whether any of these 74 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 74 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.

}, issn = {2045-2322}, doi = {10.1038/s41598-021-00123-x}, author = {Mahadevan, Jayant and Pathak, Ajai Kumar and Vemula, Alekhya and Nadella, Ravi Kumar and Viswanath, Biju and Jain, Sanjeev and Purushottam, Meera and Mondal, Mayukh} } @article {2202, title = {Psychiatric symptoms and syndromes transcending diagnostic boundaries in Indian multiplex families: The cohort of ADBS study.}, journal = {Psychiatry Res}, volume = {296}, year = {2021}, month = {2021 Feb}, pages = {113647}, abstract = {

Syndromes of schizophrenia, bipolar disorder, obsessive-compulsive disorder, substance use disorders and Alzheimer{\textquoteright}s dementia are highly heritable. About 10-20\% of subjects have another affected first degree relative (FDR), and thus represent a {\textquoteright}greater{\textquoteright} genetic susceptibility. We screened 3583 families to identify 481 families with multiple affected members, assessed 1406 individuals in person, and collected information systematically about other relatives. Within the selected families, a third of all FDRs were affected with serious mental illness. Although similar diagnoses aggregated within families, 62\% of the families also had members with other syndromes. Moreover, 15\% of affected individuals met criteria for co-occurrence of two or more syndromes, across their lifetime. Using dimensional assessments, we detected a range of symptom clusters in both affected and unaffected individuals, and across diagnostic categories. Our findings suggest that in multiplex families, there is considerable heterogeneity of clinical syndromes, as well as sub-threshold symptoms. These families would help provide an opportunity for further research using both genetic analyses and biomarkers.

}, issn = {1872-7123}, doi = {10.1016/j.psychres.2020.113647}, author = {Sreeraj, Vanteemar S and Holla, Bharath and Ithal, Dhruva and Nadella, Ravi Kumar and Mahadevan, Jayant and Balachander, Srinivas and Ali, Furkhan and Sheth, Sweta and Narayanaswamy, Janardhanan C and Venkatasubramanian, Ganesan and John, John P and Varghese, Mathew and Benegal, Vivek and Jain, Sanjeev and Reddy, Yc Janardhan and Viswanath, Biju} } @article {2156, title = {Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses.}, journal = {Aust N Z J Psychiatry}, volume = {54}, year = {2020}, month = {2020 Nov}, pages = {1086-1094}, abstract = {

OBJECTIVE: Adverse childhood experiences are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of adverse childhood experiences and their relation to the age of onset of major psychiatric conditions in individuals from families that had ⩾2 first-degree relatives with major psychiatric conditions (multiplex families), identified as part of an ongoing longitudinal study.

METHODS: Our sample consisted of 509 individuals from 215 families. Of these, 268 were affected, i.e., diagnosed with bipolar disorder ( = 61), obsessive-compulsive disorder ( = 58), schizophrenia ( = 52), substance dependence ( = 59) or co-occurring diagnoses ( = 38), while 241 were at-risk first-degree relatives who were either unaffected ( = 210) or had other depressive or anxiety disorders ( = 31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire and total adverse childhood experiences exposure and severity scores were calculated.

RESULTS: It was seen that affected males, as a group, had the greatest adverse childhood experiences exposure and severity scores in our sample. A Cox mixed effects model fit by gender revealed that a higher total adverse childhood experiences severity score was associated with significantly increased risk for an earlier age of onset of psychiatric diagnoses in males. A similar model that evaluated the interaction of diagnosis revealed an earlier age of onset in obsessive-compulsive disorder and substance dependence, but not in schizophrenia and bipolar disorder.

CONCLUSION: Our study indicates that adverse childhood experiences were associated with an earlier onset of major psychiatric conditions in men and individuals diagnosed with obsessive-compulsive disorder and substance dependence. Ongoing longitudinal assessments in first-degree relatives from these families are expected to identify mechanisms underlying this relationship.

}, issn = {1440-1614}, doi = {10.1177/0004867420931157}, author = {Someshwar, Amala and Holla, Bharath and Pansari Agarwal, Preeti and Thomas, Anza and Jose, Anand and Joseph, Boban and Raju, Birudu and Karle, Hariprasad and Muthukumaran, M and Kodancha, Prabhath G and Kumar, Pramod and Reddy, Preethi V and Kumar Nadella, Ravi and Naik, Sanjay T and Mitra, Sayantanava and Mallappagiri, Sreenivasulu and Sreeraj, Vanteemar S and Balachander, Srinivas and Ganesh, Suhas and Murthy, Pratima and Benegal, Vivek and Reddy, Janardhan Yc and Jain, Sanjeev and Mahadevan, Jayant and Viswanath, Biju} }