Stress-related reduction of hippocampal subfield volumes in major depressive disorder: A 7-Tesla study

Abstract

BackgroundMajor depressive disorder (MDD) is a prevalent health problem with complex pathophysiology that is not clearly understood. Prior work has implicated the hippocampus in MDD, but how hippocampal subfields influence or are affected by MDD requires further characterization with high-resolution data. This will help ascertain the accuracy and reproducibility of previous subfield findings in depression as well as correlate subfield volumes with MDD symptom scores. The objective of this study was to assess volumetric differences in hippocampal subfields between MDD patients globally and healthy controls (HC) as well as between a subset of treatment-resistant depression (TRD) patients and HC using automatic segmentation of hippocampal subfields (ASHS) software and ultra-high field MRI.MethodsThirty-five MDD patients and 28 HC underwent imaging using 7-Tesla MRI. ASHS software was applied to the imaging data to perform automated hippocampal segmentation and provide volumetrics for analysis. An exploratory analysis was also performed on associations between symptom scores for diagnostic testing and hippocampal subfield volumes.ResultsCompared to HC, MDD and TRD patients showed reduced right-hemisphere CA2/3 subfield volume (p = 0.01, η2 = 0.31 and p = 0.3, η2 = 0.44, respectively). Additionally, negative associations were found between subfield volumes and life-stressor checklist scores, including left CA1 (p = 0.041, f2 = 0.419), left CA4/DG (p = 0.010, f2 = 0.584), right subiculum total (p = 0.038, f2 = 0.354), left hippocampus total (p = 0.015, f2 = 0.134), and right hippocampus total (p = 0.034, f2 = 0.110). Caution should be exercised in interpreting these results due to the small sample size and low power.ConclusionDetermining biomarkers for MDD and TRD pathophysiology through segmentation on high-resolution MRI data and understanding the effects of stress on these regions can enable better assessment of biological response to treatment selection and may elucidate the underlying mechanisms of depression.

Evaluating the role of 7-Tesla magnetic resonance imaging in neurosurgery: Trends in literature since clinical approval

“…The study suggests an anatomical connectivity substrate for apathy in DBS, emphasizing the importance of considering the location of active contacts within the STN in relation to its subdivisions for understanding and potentially mitigating apathy in PD patients undergoing DBS[ 53 ]. A study aimed to explore volumetric differences in hippocampal subfields between patients with major depressive disorder (MDD), specifically treatment-resistant depression (TRD), and HCs using automatic segmentation of hippocampal subfields software with ultra-high-field 7T MRI[ 54 ]. The results revealed reduced right-hemisphere CA2/3 subfield volume in both MDD and TRD patients compared to HCs.…”

“…The study highlights the potential of high-resolution MRI data and automated segmentation techniques to identify biomarkers for MDD and TRD, providing insights into the pathophysiology of depression and potential implications for treatment selection. However, the authors acknowledge the need for caution in interpreting these results due to the small sample size and low power, emphasizing the importance of further research in this area[ 54 ].…”

An Effect of Chronic Negative Stress on Hippocampal Structures and Functional Connectivity in Patients with Depressive Disorder

“…26,27 Another study investigated the differences of hippocampal subfield volumes using 7-Tesla MRI, and analyzed the association between life-stressor and hippocampal subfield volumes, found righthemisphere CA2/3 subfield volume reduced in MDD patients, and left CA1, left CA4/DG, right subiculum total, left hippocampus total, and right hippocampus total were negatively associated with life-stressor checklist scores. 28 In summary, the evidence above suggests hypotheses that depressive disorder underwent chronic negative stress, especially the life stress, may be one potential subtype of MDD, and hippocampus may participate in the the pathogenic process of depression in those who underwent chronic stress. However, there is little research evidence now to support this hypotheses in these patients, and the role of hippocampus is worth further discussion.…”

“… 26 , 27 Another study investigated the differences of hippocampal subfield volumes using 7-Tesla MRI, and analyzed the association between life-stressor and hippocampal subfield volumes, found right-hemisphere CA2/3 subfield volume reduced in MDD patients, and left CA1, left CA4/DG, right subiculum total, left hippocampus total, and right hippocampus total were negatively associated with life-stressor checklist scores. 28 …”

An amygdala-centered effective connectivity network in trait anxiety

“…Extensive research in both rodents and humans had indicated its involvement not only in memory processes but also in anxiety (Bannerman et al, 2004 (Satpute et al, 2012). Furthermore, individuals with GAD had been found to exhibit reduced hippocampal volume compared to healthy controls (Alper et al, 2023;Bremner et al, 2000;Gray, Müller, Eickhoff, & Fox, 2020). In contrast to the amygdala's primary role in processing cues that predicted threatening or aversive stimuli, the hippocampus was crucial in processing contextual information related to threat (Alexandra Kredlow, Fenster, Laurent, Ressler, & Phelps, 2022).…”