Abstract

The extent to which heterogeneity in childhood risk trajectories may underlie later heterogeneity in schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) remains a chief question. Answers may optimally be found by studying the longitudinal trajectories of children born to an affected parent. We aimed to differentiate trajectories of global functioning and their sensitive periods from the age of 6 to 17 years in children at familial risk (FHRs). First, a latent class mixed model analysis (LCMM) was applied to yearly ratings of the Children's Global Assessment Scale (CGAS) from the age of 6 to 17 years in 170 FHRs born to a parent affected by DSM-IV SZ (N = 37), BP (N = 82) or MDD (N = 51). Then, we compared the obtained Classes or trajectories of FHRs in terms of sex, parental diagnosis, IQ, child clinical status, childhood trauma, polygenic risk score (PRS), and outcome in transition to illness. The LCMM on yearly CGAS trajectories identified a 4-class solution showing markedly different childhood and adolescence dynamic courses and temporal vulnerability windows marked by a functioning decline and a degree of specificity in parental diagnosis. Moreover, IQ, trauma exposure, PRS level, and timing of later transition to illness differentiated the trajectories. Almost half (46%) of the FHRs exhibited a good and stable global functioning trajectory. FHRsof major psychiatric disorders show heterogeneous functional decline during development associated with parental diagnosis, polygenic risk loading, and childhood trauma.

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