To the Editor We applaud Pettersson and colleagues1 for using innovative methods on a large sample of individuals to elucidate the association between gestational age–adjusted birth weight and mental health conditions. This article adds to the well-recognized role of perinatal factors (eg, birth weight) on the risk of developing depressive disorders during adolescence. As previous studies have found an association of low birth weight with depression in adolescent girls but not in boys,2,3 we invite the authors to specifically test for sex differences in their sample. eTable 9 in the Supplement1 presents results of sensitivity analyses in which slope estimates for the sex-concordant male and female pairs are of the same sign for the general factor. However, the proportion of siblings that were sex discordant is not reported. Additionally, while depression loads on the general factor, the possibility of sex differences in association of gestational age–adjusted birth weight and risk of depressive disorder cannot be ruled out. If Pettersson and colleagues1 replicate the previous findings that adolescent boys have lower risk for depression based on birth weight, it has the potential to inform studies evaluating biological mechanisms of resilience in adolescents at high risk of depression (NCT03458936). Their findings may also guide future preclinical and clinical studies of depression. Pathophysiological processes underlying depression as well as response to antidepressant medications differ between male and female individuals.4 This may be associated with, in part, the sex differences in the association of immune dysfunction with depression.5 Thus, we hope that the authors agree that the scientific contribution of their report will be enhanced by addressing any issues associated with sex differences in association with gestational age–adjusted birth weight and risk of depression during adolescence.
Jha MK, Minhajuddin A, Trivedi M. Exploring the Association of Sex Differences and Exposure to Maternal Smoking With Low Fetal Growth. JAMA Psychiatry. 2019;76(7):766–767. doi:10.1001/jamapsychiatry.2019.1116
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