Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders

Abstract

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorder (SSD, schizophrenia, and schizoaffective disorder) overlap in symptomatology, risk factors, genetics, and other biological measures. Based on previous findings, it remains unclear what transdiagnostic regional gray matter volume (GMV) alterations exist across these disorders, and with which factors they are associated. GMV (3-T magnetic resonance imaging) was compared between healthy controls (HC; n = 110), DSM-IV-TR diagnosed MDD (n = 110), BD (n = 110), and SSD patients (n = 110), matched for age and sex. We applied a conjunction analysis to identify shared GMV alterations across the disorders. To identify potential origins of identified GMV clusters, we associated them with early and current risk and protective factors, psychopathology, and neuropsychology, applying multiple regression models. Common to all diagnoses (vs. HC), we identified GMV reductions in the left hippocampus. This cluster was associated with the neuropsychology factor working memory/executive functioning, stressful life events, and with global assessment of functioning. Differential effects between groups were present in the left and right frontal operculae and left insula, with volume variances across groups highly overlapping. Our study is the first with a large, matched, transdiagnostic sample to yield shared GMV alterations in the left hippocampus across major mental disorders. The hippocampus is a major network hub, orchestrating a range of mental functions. Our findings underscore the need for a novel stratification of mental disorders, other than categorical diagnoses.

Fig. 1. Significant clusters exhibiting GMV differences between HC, MDD, BD, and SSD (F-Test).

Combined boxplots and violin plots show value distribution for the groups in the respective cluster.

Fig. 2. Post-hoc comparisons of healthy controls - patients.

HC > SSD clusters are presented in purple; HC > MDD cluster is presented in yellow.

Fig. 3. Post-hoc within patient comparisons.

GMV differences were present for MDD > SSD (orange) and BD > SSD (green); for details see Table 2.

Fig. 4. Hippocampal volume reductions in all patients compared to healthy controls.

Results from the conjunction analysis (HC > MDD ∩ HC > BD ∩ HC > SSD): GMV reductions common in all diagnoses compared to HC in the left hippocampus, (k = 316, x/y/z = −30/−33/−10.5), T = 4.25, p = 0.042 FWE cluster level.