Hippocampal subfield alterations in schizophrenia and major depressive disorder: a systematic review and network meta-analysis of anatomic MRI studies

Abstract

Background: Hippocampal disturbances are important in the pathophysiology of both schizophrenia and major depressive disorder (MDD). Imaging studies have shown selective volume deficits across hippocampal subfields in both disorders. We aimed to investigate whether these volumetric alterations in hippocampal subfields are shared or divergent across disorders. Methods: We searched PubMed and Embase from database inception to May 8, 2021. We identified MRI studies in patients with schizophrenia, MDD or both, in which hippocampal subfield volumes were measured. We excluded nonoriginal, animal or postmortem studies, and studies that used other imaging modalities or overlapping data. We conducted a network meta-analysis to estimate and contrast alterations in subfield volumes in the 2 disorders. Results: We identified 45 studies that met the initial criteria for systematic review, of which 15 were eligible for network metaanalysis. Compared to healthy controls, patients with schizophrenia had reduced volumes in the bilateral cornu ammonis (CA) 1, granule cell layer of the dentate gyrus, subiculum, parasubiculum, molecular layer, hippocampal tail and hippocampus-amygdala transition area (HATA); in the left CA4 and presubiculum; and in the right fimbria. Patients with MDD had decreased volumes in the left CA3 and CA4 and increased volumes in the right HATA compared to healthy controls. The bilateral parasubiculum and right HATA were smaller in patients with schizophrenia than in patients with MDD. Limitations: We did not investigate medication effects because of limited information. Study heterogeneity was noteworthy in direct comparisons between patients with MDD and healthy controls. Conclusion: The volumes of multiple hippocampal subfields are selectively altered in patients with schizophrenia and MDD, with overlap and differentiation in subfield alterations across disorders. Rigorous head-to-head studies are needed to validate our findings.

Hippocampal subfield volumes in treatment resistant depression and serial ketamine treatment

“…However, increases in left CA3, CA4, and GC.ML.DG volumes from baseline to 5-week follow up trended toward significance, suggesting possible longer-term effects of ketamine on hippocampal structure. Finally, consistent with prior findings in the field suggested that depression was associated with smaller hippocampal volume ( 42 , 43 ), we found that patients with TRD relative to HC had smaller left CA4 and GC.ML.DG baseline volumes.…”

“…In this study, we found that patients with TRD had significantly smaller pre-treatment volumes in the left CA4 and GC.ML.DG when compared to HC. Reduced volumes of CA1 ( 43 , 46 ), CA3 ( 42 , 43 , 46 ), CA4 ( 42 , 43 ), and GC.ML.DG ( 42 ), have been reported in patients with MDD when compared to healthy controls, although the laterality of reports vary. There are several theories that speculate about the underlying biological mechanism driving reduced hippocampal volume observed in patients with depression ( 51 ).…”

Specific amygdala and hippocampal subfield volumes in social anxiety disorder and their relation to clinical characteristics – an international mega-analysis

“…Studies of amygdala subfield volumes in MDD suggest that the lateral and anterior amygdaloid areas are smaller in individuals with MDD compared to HCs (individuals with SAD=147; HCs=144) 64 , whilst other studies report null findings (patient=76; HC=77) 65 . The present findings of larger hippocampal subfield volumes further contrast with recent meta-analyses which suggest that MDD is associated with smaller hippocampal CA3, CA4 and larger HATA volumes, compared to HCs 23 . The fact that only the AB remained significant suggests that major depression comorbidity may have an influence on subfield volumes in SAD.…”

“…Given the roles of the amygdala and hippocampus in fear and anxiety 20,21 , and developments in amygdala and hippocampal segmentation techniques (Saygin et al, 2017), there have been increasing reports of subfield volume alterations in anxiety-related disorders 22 . Reviews of the hippocampal subfields literature suggest that individuals with MDD have smaller volumes of the CA3/4 and larger volume of the hippocampus–amygdala transition area (HATA) compared to HCs 23 , while individuals with PTSD have smaller volumes of the CA1/3 and dentate gyrus (DG) compared to HCs (Ben-Zion et al, 2023). Moreover, Koch and colleagues (2021) found that a smaller dentate gyrus volume prospectively predicted PTSD vulnerability.…”

Adult hippocampal neurogenesis: pharmacological mechanisms of antidepressant active ingredients in traditional Chinese medicine

“…Pathological abnormalities in the hippocampus have been extensively investigated in relation to MDD ( Belleau et al, 2019 ). A study conducted a comparative analysis of Magnetic Resonance Imaging (MRI) results between MDD patients and a healthy control group, unveiling a reduction in the volume of the left hippocampal CA3 and CA4 regions, alongside an elevation in the volume of the right hippocampal amygdala transition area (HATA) ( Sun et al, 2023 ). Another report identified hippocampal atrophy in MDD patients experiencing anhedonia, specifically in the left CA1 and DG subfields, which may be associated with the lack of pleasure endemic to MDD ( Wu et al, 2023 ).…”