Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study's purpose was to investigate family history's effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18-65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala compared to patients with a MDD family history.MDD without family history also had larger right amygdala than healthy controls without MDD family history.These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants providing rationale for the inconsistent results in MDD amygdala studies [corrected]. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.
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