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Marie B. H. Yap, PhD; Sarah Whittle, PhD; Murat Yücel, PhD; Lisa Sheeber, PhD; Christos Pantelis, MD, MRCPsych, FRANZCP; Julian G. Simmons, BSc; Nicholas B. Allen, PhD

Arch Gen Psychiatry. 2008;65(12):1377-1385.

Context  Although some evidence suggests that neuroanatomic abnormalities may confer risk for major depressive disorder, findings are inconsistent. One potential explanation for this is the moderating role of environmental context, with individuals differing in their biological sensitivity to context.

Objective  To examine the influence of adverse parenting as an environmental moderator of the association between brain structure and depressive symptoms.

Design  Cross-sectional measurement of brain structure, adverse parenting, and depressive symptoms in early adolescents.

Setting  General community.

Participants  A total of 106 students aged 11 to 13 years (55 males [51%]), recruited from primary schools in Melbourne, Australia, and their mothers. Selection was based on affective temperament, aimed at producing a sample representing a broad range of risk for major depressive disorder. No participant evidenced current or past case-level depressive, substance use, or eating disorder.

Main Outcome Measures  (1) Volumetric measures of adolescents' amygdala, hippocampus, and anterior cingulate cortex (ACC); (2) frequency of observed maternal aggressive behavior during a mother-adolescent conflict-resolution interaction; and (3) adolescent depressive symptoms.

Results  Boys with smaller right amygdalas reported more depressive symptoms. However, neither hippocampal volume nor asymmetry measures of limbic or paralimbic ACC were directly related to level of depressive symptoms. Importantly, frequency of maternal aggressive behaviors moderated the associations between both the amygdala and ACC, and adolescent symptoms. Particularly, in conditions of low levels of maternal aggressiveness, boys with larger right amygdalas, girls with smaller bilateral amygdalas, and both boys and girls with smaller left paralimbic ACC reported fewer symptoms.

Conclusions  These findings help elucidate the complex relationships between brain structure, environmental factors, and depressive symptoms. Further longitudinal research is required to examine how these factors contribute to the onset of case-level disorder, but given that family context risk factors are modifiable, our findings do suggest the potential utility of targeted early parenting interventions.

Author Affiliations: ORYGEN Research Centre (Drs Yap, Whittle, Yücel, and Allen and Mr Simmons) and Melbourne Neuropsychiatry Centre (Drs Whittle, Yücel, and Pantelis), Department of Psychiatry, and Department of Psychology (Drs Yap, Whittle, and Allen and Mr Simmons), The University of Melbourne, and Melbourne Health (Drs Whittle, Yücel, and Pantelis), Parkville, Victoria, Australia; and Oregon Research Institute, Eugene (Dr Sheeber).

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