Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress

Abstract

Medial temporal lobe structures have long been implicated in the pathogenesis of major depressive disorder. Although findings of smaller hippocampal and amygdalar volumes are common, inconsistencies remain in the literature. In this targeted review, we examine recent and significant neuroimaging papers examining the volumes of these structures in major depressive disorder. A targeted PubMed/Google Scholar search was undertaken focusing on volumetric neuroimaging studies of the hippocampus and amygdala in major depressive disorder. Where possible, mean volumes and accompanying standard deviations were extracted allowing computation of Cohen’s ds effect sizes. Although not a meta-analysis, this allows a broad comparison of volume changes across studies. Thirty-nine studies in total were assessed. Hippocampal substructures and amygdale substructures were investigated in 11 and 2 studies, respectively. The hippocampus was more consistently smaller than the amygdala across studies, which is reflected in the larger cumulative difference in volume found with the Cohen’s ds calculations. The left and right hippocampi were, respectively, 92% and 91.3% of the volume found in controls, and the left and right amygdalae were, respectively, 94.8% and 92.6% of the volume of controls across all included studies. The role of stress in temporal lobe structure volume reduction in major depressive disorder is discussed.

Amygdala substructure volumes in Major Depressive Disorder

“…The experiential aspects of MDD theoretically map onto brain limbic circuitry, in particular the subcortical temporal lobe limbic structures of the hippocampus and the amygdala ( Kaiser et al, 2015 , Pruessner et al, 2010 ). Evidence indicates that state depression is associated with reduced hippocampal volumes ( Brown et al, 2014 , Nolan et al, 2020 , Schmaal et al, 2016 , Stephanie Campbell et al, 2004 , Wise et al, 2017 ). Hippocampal pathology is consistent with the key cognitive difficulties experienced in MDD, such as impairments in short term and autobiographical memory formation ( Kohler et al, 2015 ) and attentional problems ( Disner et al, 2011 ).…”

Understanding Emotions: Origins and Roles of the Amygdala

“…While increased amygdala activation was observed in patients with bipolar disorder across all illness phases, similar findings were also observed during attention tasks that had no emotional components, suggesting the additional role of the amygdala in cognition [286]. A recent meta-analysis reported smaller amygdala volumes in participants with major depressive disorder (MDD) compared to healthy controls, although greater differences between groups were observed for hippocampal volume [287]. Interestingly, amygdala volumes in bipolar patients did not differ from healthy controls [288].…”

Volume of Amygdala Subregions and Clinical Manifestations in Patients With First-Episode, Drug-Naïve Major Depression

“…For example, previous studies of the amygdala and hippocampus have reported reduced volume as a potential biomarker of depression (Roddy et al, 2019;Sheline et al, 2019). According to 12 studies reported so far, a 5.2% decrease in the left amygdala and a 7.4% decrease in the right amygdala have been reported in depression (Nolan et al, 2020). Notwithstanding, there are fewer reports on amygdala volume than on hippocampal volume, and there is a lack of assessment of the amygdala in relation to depression.…”