TY - JOUR

T1 - A study of the genetic architecture of social responsiveness in families with parental schizophrenia or bipolar disorder and population-based controls

AU - Veddum, Lotte

AU - Greve, Aja Neergaard

AU - Gregersen, Maja

AU - Andreassen, Anna Krogh

AU - Knudsen, Christina Bruun

AU - Brandt, Julie Marie

AU - Krantz, Mette Falkenberg

AU - Søndergaard, Anne

AU - Burton, Birgitte Klee

AU - Jepsen, Jens Richardt Møllegaard

AU - Hemager, Nicoline

AU - Werge, Thomas

AU - Thorup, Anne Amalie Elgaard

AU - Nordentoft, Merete

AU - Mors, Ole

AU - Nudel, Ron

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Twin-studies of social responsiveness have reported moderate to high heritabilities, but studies using parent–child data are lacking. Additionally, social impairments have been suggested as a vulnerability marker for schizophrenia and bipolar disorder, but the heritability of social responsiveness in this context is unknown. This study is part of the Danish High Risk and Resilience Study – VIA, comprising families with one parent with schizophrenia (n = 202) or bipolar disorder (n = 120) and population-based controls (PBC, n = 200). Social responsiveness was assessed with The Social Responsiveness Scale, Second Edition (SRS-2). Heritability was estimated from variance components, and a polygenic risk score (PRS) for autism spectrum disorder (ASD) was calculated to assess the genetic relationship between ASD and SRS-2. SRS-2 heritability was moderate to high and significantly different from zero in all groups when the children were rated by the primary caregiver. With teacher ratings, the heritability was lower and only significant in the full cohort and PBC. We found no significant association between SRS-2 and PRS for ASD. Our study confirms that social responsiveness is heritable, but that heritability estimates are affected by the child-respondent relation and familial risk of mental illness. This has implications for clinical practice and research using SRS-2 and provides insight on the familial transmission of mental illness.

AB - Twin-studies of social responsiveness have reported moderate to high heritabilities, but studies using parent–child data are lacking. Additionally, social impairments have been suggested as a vulnerability marker for schizophrenia and bipolar disorder, but the heritability of social responsiveness in this context is unknown. This study is part of the Danish High Risk and Resilience Study – VIA, comprising families with one parent with schizophrenia (n = 202) or bipolar disorder (n = 120) and population-based controls (PBC, n = 200). Social responsiveness was assessed with The Social Responsiveness Scale, Second Edition (SRS-2). Heritability was estimated from variance components, and a polygenic risk score (PRS) for autism spectrum disorder (ASD) was calculated to assess the genetic relationship between ASD and SRS-2. SRS-2 heritability was moderate to high and significantly different from zero in all groups when the children were rated by the primary caregiver. With teacher ratings, the heritability was lower and only significant in the full cohort and PBC. We found no significant association between SRS-2 and PRS for ASD. Our study confirms that social responsiveness is heritable, but that heritability estimates are affected by the child-respondent relation and familial risk of mental illness. This has implications for clinical practice and research using SRS-2 and provides insight on the familial transmission of mental illness.

KW - Familial high-risk

KW - Polygenic risk score

KW - Severe mental illness

KW - SRS-2

U2 - 10.1016/j.psychres.2023.115280

DO - 10.1016/j.psychres.2023.115280

M3 - Journal article

C2 - 37339530

AN - SCOPUS:85161970591

VL - 326

JO - Psychiatry Research

JF - Psychiatry Research

SN - 0165-1781

M1 - 115280

ER -