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A Test of Competing Hypotheses

Elizabeth Jane Costello, PhD; Carol Worthman, PhD; Alaattin Erkanli, PhD; Adrian Angold, MRCPsych

Arch Gen Psychiatry. 2007;64(3):338-344.

Context  Low birth weight (LBW) predicts later-onset hypertension and diabetes mellitus. Its role as a predictor of depression is unclear.

Objectives  To examine whether LBW predicts depression in male and female children and adolescents and to compare the following 2 hypotheses: Low birth weight is one among several perinatal, childhood, and adolescent risk factors for depression (biopsychosocial hypothesis). Low birth weight is a marker for poor intrauterine conditions that provoke adjustments in fetal development, with long-term consequences for stress response (fetal programming hypothesis).

Design  A representative population-based sample from an 11-county area in western North Carolina was assessed annually for psychiatric disorders between the ages of 9 and 16 years. We tested the prediction from LBW and depression in models that included LBW only, LBW plus other prenatal and perinatal adversities, LBW plus significant perinatal and childhood adversities, and LBW plus significant perinatal and childhood adversities and adolescent correlates.

Setting  Academic research.

Participants  There were 1420 participants, of whom 49% were female.

Main Outcome Measure  Cumulative prevalence of DSM-IV depressive disorder at 1 assessment or more during childhood (age range, 9-12 years) and during adolescence (age range, 13-16 years).

Results  The cumulative prevalence of depression among adolescent girls with LBW was 38.1% (95% confidence interval [CI], 16.3%-66.0%) compared with 8.4% (95% CI, 5.2%-13.3%) among adolescent girls with normal birth weight. Rates among children and adolescent boys did not exceed 4.9%. In adolescence, there was a significant interaction between LBW and sex (odds ratio, 0.2 [95% CI, 0.1-0.5]; P<.001). Low birth weight predicted female adolescent depression after controlling for other perinatal, childhood, and adolescent adversities. Girls with LBW and normal birth weight with no adversities had no adolescent depression, but each additional adversity increased the risk of in girls with LBW more than in girls with normal birth weight. Low birth weight did not predict other psychiatric disorders in either sex.

Conclusions  Low birth weight predicts depression in adolescent girls but not boys. Data support fetal programming over the biopsychosocial hypothesis, suggesting vulnerability to adversities in girls with LBW after puberty.

Author Affiliations: Center for Developmental Epidemiology, Department of Psychiatry and Behavioral Sciences (Drs Costello and Angold), and Department of Biostatistics (Dr Erkanli), Duke University Medical School, Durham, NC; and Department of Anthropology, Emory University, Atlanta, Ga (Dr Worthman).

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