Subgenual anterior cingulate cortex and hippocampal volumes in depressed youth: The role of comorbidity and age

Objectives: Many studies have reported that adults with recurrent major depressive disorder (MDD) have smaller hippocampal volumes than control participants. The data are more variable in youth with MDD, where findings have been inconsistent and the effects of factors such as age and co-morbidity have not been systematically examined. This study therefore assessed hippocampus and subgenual anterior cingulate (sgACC) morphometry in 168 youth, aged 12-25, with or without MDD and comorbid anxiety.

Methods: Structural magnetic resonance imaging (MRI) scans and clinical assessments were obtained from 80 participants with MDD (36 with comorbid anxiety disorder) and 88 age-matched control participants.

Results: Participants with MDD had smaller right hippocampi than controls (p=.013). Older depressed participants (20.1-25 years) had smaller hippocampal volumes than younger ones (<20.1 years; p=.05); this age effect was not apparent in controls (p=.46). Depression scores, indexed by the HAMD17, correlated with hippocampal volumes in older depressed youth. Depressed participants with comorbid anxiety had smaller sgACC, but not hippocampal, volumes than those without anxiety (p=.042).

Limitations: Longitudinal, versus cross-sectional, studies can most optimally assess the influence of depression on neurodevelopmental profiles. Though our participants were largely treatment-naïve or in their first week of pharmacotherapy, a handful had extensive treatment histories; thus, treatment history may have influenced brain morphometry.

Conclusions: Age effects were apparent when hippocampal volumes of older and younger participants with MDD were compared; such differences were not apparent in healthy participants. Comorbid anxiety was associated with decreased sgACC volumes suggesting delayed or altered neurodevelopment in a key emotion regulation region.