Hippocampal Atrophy in Major Depression: a Function of Childhood Maltreatment Rather than Diagnosis?

Abstract

Reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with major depressive disorder (MDD). However, it remains unclear whether altered hippocampal structure represents a risk factor for or a consequence of MDD. Reduced hippocampal volumes were consistently reported in subjects affected by childhood maltreatment. As the prevalence of childhood maltreatment is highly elevated in MDD populations, previous morphometric findings regarding hippocampal atrophy in MDD therefore might have been confounded by maltreatment experiences. The aim of this study was to differentiate the impact of childhood maltreatment from the influence of MDD diagnosis on hippocampal morphometry. Depressed patients (85) as well as 85 age-and sex-matched healthy controls underwent structural MRI. The Childhood Trauma Questionnaire was administered to estimate experiences of childhood maltreatment. Hippocampal volume and surface structure was examined by the use of two independent methods, automated segmentation (FSL-FIRST) and voxel-based morphometry (VBM8). In line with existing studies, MDD patients showed reduced hippocampal volumes, and childhood maltreatment was consistently associated with hippocampal volume loss in both, patients and healthy controls. However, no analysis revealed significant morphological differences between patients and controls if maltreatment experience was regressed out. Our results suggest that hippocampal alterations in MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.

Prefrontal brain responsiveness to negative stimuli

“…To assess the influence of psychopharmacological therapy in the MDD sample, medication load was coded in terms of dose and treatment durations into levels 1-4 according to the suggestions of Sackeim 14 and as conducted previously by our group and others. [15][16][17] To be included, patients with MDD had to be free from psychotic symptoms according to the SCID-I. 13 We assessed family history of depression in the MDD-FH+, the MDD-FH-and the HC-FH-samples via familial anamnesis.…”

“…This was performed by means of the AlphaSim procedure, which accounted for spatial correlations between grey matter values in neighbouring voxels, implemented in the REST toolbox (http://restfmri.net/forum/index.php). 16,[29][30][31] The cluster threshold calculation was based on a residual smoothness value of 10 mm FWHM, as estimated with SPM8. The empirically determined cluster threshold was k = 26 voxels for the medial OFC and k = 40 voxels for the bilateral DLPFC.…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…Other VBM studies have also found structural abnormalities in regions including the insula, thalamus, and hippocampus in MDD patients [28,[35][36][37][38][39][40][41][42][43]. The anterior insula connects to the inferior frontal cortex and to the ACC [44].…”

A relationship between early life stress and depression: the role of the serotonin transporter gene polymorphism (5-HTTLPR)

“…The hippocampus is functionally important for long-term memory storage of episodic events as well as emotion and mood regulation [69]. A number of studies have linked hippocampal abnormalities with early life stress and depression [70][71][72][73]. Evidence suggests 5-HTTLPR may play an important role in explaining this relationship.…”