The Hippocampus in Depression: More Than the Sum of Its Parts? Advanced Hippocampal Substructure Segmentation in Depression

Roddy, Darren; Farrell, Chloë; Doolin, Kelly; Román, Elena; Tozzi, Leonardo; Frodl, Thomas; O’Keane, Veronica; O’Hanlon, Erik

doi:10.1016/j.biopsych.2018.08.021

Cited by 175 publications

(136 citation statements)

References 70 publications

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“…Our results extend prior work showing smaller volumes in the CA1 among individuals with C-PTSD and depression (36,43,44), and suggest that CA1 integrity is more vulnerable to the effects of depression than PTSD. CA1 volume differences may reflect stress-induced alterations in negative feedback projections from the hippocampus to the hypothalamus, which are principally supplied by the CA1 pyramidal cell (7,54).…”

Section: Potential Mechanisms Underlying Morphometry In the Ca1supporting

confidence: 88%

“…To confirm the regional specificity of our findings, we performed post-hoc comparisons of combinations of subfields using recent methods outlined by Roddy et al (44). We created the following nine composites based on structure-function synergies defined in the literature (39,44,46,48 complete dentate (CA4/DG); 5) CA-only (CA1-3); 6) Sub-complex (subiculum, presubiculum, parasubiculum); 7) CA1/sub (CA1+subiculum); 8) CA/SubPresub/MOL (CA1-3, subiculum, presubiculum, MOL); and 9) hippocampal extended (sum of all subfields minus the fissure). 1 Additional details are in the Supplement.…”

Section: Sensitivity Analysis Of Composite Subregionsmentioning

confidence: 92%

“…Concurrent clinical and sociodemographic factors may also exert independent or additive effects on substructural hippocampal volumes. In particular, depression occurs in 30-60% of PTSD patients and has been associated with reduced integrity of the same subfields implicated in PTSD (35,(41)(42)(43)(44). Additional factors such as childhood trauma, alcohol use disorder (AUD), and traumatic brain injury (TBI) may alter the hippocampus but are variably represented across PTSD samples.…”

Section: Introductionmentioning

confidence: 99%

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Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

Salminen

Sämann

Zheng

et al. 2019

Preprint

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Background: PTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression. Methods:We used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115;Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.Results: A significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=-0.13) and CA1 (ß=-0.09) after adjusting for covariates and multiple testing (adjusted p's (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=-0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=-0.12, q=0.012), C-PTSD-only (ß=-0.17, q=0.001), and Depression-only (ß=-0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males. Conclusions:Collectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.

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Section: Potential Mechanisms Underlying Morphometry In the Ca1supporting

confidence: 88%

Section: Sensitivity Analysis Of Composite Subregionsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

Salminen

Sämann

Zheng

et al. 2019

Preprint

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“…Indeed, all of the subcortical structures that have been implicated in MDD contain functionally distinct subregions (Roddy et al 2018). For example, the hippocampus is not a singular unit, but consists of several subregions, including the cornu ammonis subfields (CA) 1-4, dentate gyrus (DG), and the subiculum (SUB).…”

Section: Introductionmentioning

confidence: 99%

Subcortical Shape Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group

Gutman

Pozzi

et al. 2019

Preprint

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Word Count: 247 Full Text Word Count: 5192 Figures: 3 Tables: 1 Supplement: 1Abstract Alterations in regional subcortical brain volumes have been widely investigated as part of the efforts of an international consortium, ENIGMA, to determine reliable structural brain signatures for Major Depressive Disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work to precisely map localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus.Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with MDD had lower surface area in the subiculum of the hippocampus, the basolateral amygdala, and the nucleus accumbens shell. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum of the hippocampus and the basolateral amygdala. Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala.Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

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“…The functional diversity (Poppenk et al, 2013;Strange et al, 2014) and structural complexity (Duvernoy, 2005) of the hippocampus suggest the existence of subdivisions within this region. The parcellation of the hippocampus into subdivisions may provide critical insights regarding the roles of the hippocampus in physiological and pathological states, including Alzheimer's disease (Iglesias et al, 2015), major depressive disorder (Roddy et al, 2019), and schizophrenia (Arnold et al, 2014), because these techniques offer a valuable tool to explore such critical questions (Eickhoff, Thirion, Varoquaux, & Bzdok, 2015;Fan et al, 2016;Glasser et al, 2016).…”

mentioning

confidence: 99%

Parcellation of the human hippocampus based on gray matter volume covariance: Replicable results on healthy young adults

Kot

Liu

et al. 2019

Human Brain Mapping

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The hippocampus is a key brain region that participates in a range of cognitive and affective functions, and is involved in the etiopathogenesis of numerous neuropsychiatric disorders. The structural complexity and functional diversity of the hippocampus suggest the existence of structural and functional subdivisions within this structure. For the first time, we parcellated the human hippocampus with two independent data sets, each of which consisted of 198 T1‐weighted structural magnetic resonance imaging (sMRI) images of healthy young subjects. The method was based on gray matter volume (GMV) covariance, which was quantified by a bivariate voxel‐to‐voxel linear correlation approach, as well as a multivariate masked independent component analysis approach. We subsequently interrogated the relationship between the GMV covariance patterns and the functional connectivity patterns of the hippocampal subregions using sMRI and resting‐state functional MRI (fMRI) data from the same participants. Seven distinct GMV covariance‐based subregions were identified for bilateral hippocampi, with robust reproducibility across the two data sets. We further demonstrated that the structural covariance patterns of the hippocampal subregions had a correspondence with the intrinsic functional connectivity patterns of these subregions. Together, our results provide a topographical configuration of the hippocampus with converging structural and functional support. The resulting subregions may improve our understanding of the hippocampal connectivity and functions at a subregional level, which provides useful parcellations and masks for future neuroscience and clinical research on the structural and/or functional connectivity of the hippocampus.

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The Hippocampus in Depression: More Than the Sum of Its Parts? Advanced Hippocampal Substructure Segmentation in Depression

Cited by 175 publications

References 70 publications

Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

Subcortical Shape Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group

Parcellation of the human hippocampus based on gray matter volume covariance: Replicable results on healthy young adults

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