%0 Journal Article %J Aust N Z J Psychiatry %D 2020 %T Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses. %A Someshwar, Amala %A Holla, Bharath %A Pansari Agarwal, Preeti %A Thomas, Anza %A Jose, Anand %A Joseph, Boban %A Raju, Birudu %A Karle, Hariprasad %A Muthukumaran, M %A Kodancha, Prabhath G %A Kumar, Pramod %A Reddy, Preethi V %A Kumar Nadella, Ravi %A Naik, Sanjay T %A Mitra, Sayantanava %A Mallappagiri, Sreenivasulu %A Sreeraj, Vanteemar S %A Balachander, Srinivas %A Ganesh, Suhas %A Murthy, Pratima %A Benegal, Vivek %A Reddy, Janardhan Yc %A Jain, Sanjeev %A Mahadevan, Jayant %A Viswanath, Biju %X

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.

%B Aust N Z J Psychiatry %V 54 %P 1086-1094 %8 2020 Nov %G eng %N 11 %R 10.1177/0004867420931157 %0 Journal Article %J Psychiatry Clin Neurosci %D 2019 %T Exome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes. %A Ganesh, Suhas %A Ahmed P, Husayn %A Nadella, Ravi K %A More, Ravi P %A Seshadri, Manasa %A Viswanath, Biju %A Rao, Mahendra %A Jain, Sanjeev %A Mukherjee, Odity %K Bipolar Disorder %K Exome %K Female %K Genetic Predisposition to Disease %K Genetic Variation %K Genome-Wide Association Study %K Humans %K Male %K Pedigree %K Phenotype %K Schizophrenia %X

AIM: Severe mental illnesses (SMI), such as bipolar disorder and schizophrenia, are highly heritable, and have a complex pattern of inheritance. Genome-wide association studies detect a part of the heritability, which can be attributed to common genetic variation. Examination of rare variants with next-generation sequencing may add to the understanding of the genetic architecture of SMI.

METHODS: We analyzed 32 ill subjects from eight multiplex families and 33 healthy individuals using whole-exome sequencing. Prioritized variants were selected by a three-step filtering process, which included: deleteriousness by five in silico algorithms; sharing within families by affected individuals; rarity in South Asian sample estimated using the Exome Aggregation Consortium data; and complete absence of these variants in control individuals from the same gene pool.

RESULTS: We identified 42 rare, non-synonymous deleterious variants (~5 per pedigree) in this study. None of the variants were shared across families, indicating a 'private' mutational profile. Twenty (47.6%) of the variant harboring genes were previously reported to contribute to the risk of diverse neuropsychiatric syndromes, nine (21.4%) of which were of Mendelian inheritance. These included genes carrying novel deleterious variants, such as the GRM1 gene implicated in spinocerebellar ataxia 44 and the NIPBL gene implicated in Cornelia de Lange syndrome.

CONCLUSION: Next-generation sequencing approaches in family-based studies are useful to identify novel and rare variants in genes for complex disorders like SMI. The findings of the study suggest a potential phenotypic burden of rare variants in Mendelian disease genes, indicating pleiotropic effects in the etiology of SMI.

%B Psychiatry Clin Neurosci %V 73 %P 11-19 %8 2019 Jan %G eng %N 1 %R 10.1111/pcn.12788