Familial risk for depressive and anxiety disorders: associations with genetic, clinical, and psychosocial vulnerabilities

Background In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account. Methods Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety. Results Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma. Conclusions Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure.