%0 Journal Article %J J Psychiatr Res %D 2021 %T Cross-diagnostic evaluation of minor physical anomalies in psychiatric disorders. %A Sreeraj, Vanteemar S %A Puzhakkal, Joan C %A Holla, Bharath %A Nadella, Ravi Kumar %A Sheth, Sweta %A Balachander, Srinivas %A Ithal, Dhruva %A Ali, Furkhan %A Viswanath, Biju %A Muralidharan, Kesavan %A Venkatasubramanian, Ganesan %A John, John P %A Benegal, Vivek %A Murthy, Pratima %A Varghese, Mathew %A Reddy, Yc Janardhan %A Jain, Sanjeev %X

BACKGROUND: Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia).

METHODS: Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO).

RESULTS: MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders.

CONCLUSION: MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.

%B J Psychiatr Res %V 142 %P 54-62 %8 2021 Jul 20 %G eng %R 10.1016/j.jpsychires.2021.07.028 %0 Journal Article %J Psychiatry Res %D 2021 %T Psychiatric symptoms and syndromes transcending diagnostic boundaries in Indian multiplex families: The cohort of ADBS study. %A Sreeraj, Vanteemar S %A Holla, Bharath %A Ithal, Dhruva %A Nadella, Ravi Kumar %A Mahadevan, Jayant %A Balachander, Srinivas %A Ali, Furkhan %A Sheth, Sweta %A Narayanaswamy, Janardhanan C %A Venkatasubramanian, Ganesan %A John, John P %A Varghese, Mathew %A Benegal, Vivek %A Jain, Sanjeev %A Reddy, Yc Janardhan %A Viswanath, Biju %X

Syndromes of schizophrenia, bipolar disorder, obsessive-compulsive disorder, substance use disorders and Alzheimer's dementia are highly heritable. About 10-20% of subjects have another affected first degree relative (FDR), and thus represent a 'greater' 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.

%B Psychiatry Res %V 296 %P 113647 %8 2021 Feb %G eng %R 10.1016/j.psychres.2020.113647