Global hippocampal atrophy in major depressive disorder: a meta-analysis of magnetic resonance imaging studies

Santos, Marcelo; Bezerra, Lucas Soares; Carvalho, Ana Rita Marinho Ribeiro; Brainer-Lima, Alessandra Mertens

doi:10.1590/2237-6089-2017-0130

Cited by 132 publications

(36 citation statements)

References 48 publications

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“…We observed significant differences in adult MDD patients in WM tracts that lead to the hippocampus, including the fornix/stria terminalis and the hippocampal portion of the cingulum bundle. Smaller hippocampal volumes (on average) is one of the most consistently reported neuroimaging findings in the depression literature (for meta-analyses please see [3,51]). Similar mechanisms may underlie both findings.…”

Section: Discussionmentioning

confidence: 99%

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

et al. 2019

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Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

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Section: Discussionmentioning

confidence: 99%

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

et al. 2019

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“…We focused our gene expression and electrophysiological studies on the hippocampus, which has been strongly implicated in mood-related disorders [127][128][129] . Early stress influences both hippocampal neuronal morphology and plasticity, features that contribute to the behavioral sequelae of early trauma [130][131][132][133] .…”

Section: Discussionmentioning

confidence: 99%

Chronic chemogenetic activation of forebrain excitatory neurons in postnatal life evokes long-lasting changes in mood-related behavior

Pati

Saba

et al. 2020

Preprint

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Early adversity is a key risk factor for the development of adult psychopathology, including anxiety, depression and schizophrenia. Rodent models of early adversity program persistent behavioral, molecular, metabolic, and neurophysiological changes. Perturbed signaling via forebrain Gq-coupled neurotransmitter receptors is a common feature across multiple models of early adversity. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke long-lasting mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated chemogenetic activation of CamKIIα-positive forebrain excitatory neurons during postnatal life (P2-14) increased anxietyand despair-like behavior, and evoked sensorimotor gating deficits in adulthood. In contrast, chronic chemogenetic hM3Dq DREADD activation of forebrain excitatory neurons in the juvenile or adult window did not evoke any mood-related behavioral alterations, highlighting the criticality of the postnatal temporal window. The enhanced anxiety-, despair-and schizophrenia-like behavioral changes evoked by chronic chemogenetic activation of forebrain excitatory neurons in postnatal life, was accompanied by an increased cortical and hippocampal metabolic rate of glutamatergic and GABAergic neurons in adulthood. Furthermore, animals with a history of postnatal hM3Dq activation exhibited a decline in the expression of activitydependent and plasticity-associated markers within the hippocampus, along with perturbed hippocampal excitatory and inhibitory currents in adulthood. These results indicate that Gq signaling mediated activation of forebrain excitatory neurons during the critical postnatal window is sufficient to program altered mood-related behavior, as well as metabolic and neurophysiological changes in forebrain glutamate and GABA systems, recapitulating specific aspects of the consequences of early adversity.

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“…Depression is recognized not to result from any specific pathology affecting only single-cell types or areas but is characterized by altered functioning of a more complex cortico-limbic circuitry. The medial prefrontal cortex, particularly the subgenual cingulate cortex (SCC), along with connecting subcortical structures, such as the hippocampus (Videbech and Ravnkilde, 2004;Kempton et al, 2011;Santos et al, 2018), the amygdala, and the nucleus accumbens, are affected (Ressler and Mayberg, 2007;Heshmati and Russo, 2015;Akil et al, 2018). Hyperactive hypothalamus-pituitary adrenal axis and the overproduction of stress hormones, decreased neurotrophic support, and reduced neuronal plasticity are thought to underlie some of the atrophic changes associated with depression (Lee et al, 2002;Duman and Monteggia, 2006;Castrén et al, 2007;Liu et al, 2017).…”

Section: The Neurobiological Premise Of Major Depressionmentioning

confidence: 99%

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

Rantamäki

Kohtala

2020

Pharmacol Rev

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Brain and Mind Doctoral Program (S.K.), the Orion Research Foundation (S.K.), and the Emil Aaltonen foundation (S.K.). T.R. and S.K. are listed as coinventors on a patent application, wherein new tools enabling the development of rapid-acting antidepressants and the efficacy monitors thereof are disclosed based on the basic principles of ENCORE-D. T.R. and S.K. have assigned their patent rights to the University of Helsinki but will share a percentage of any royalties that may be received by the University of Helsinki.

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Global hippocampal atrophy in major depressive disorder: a meta-analysis of magnetic resonance imaging studies

Abstract: MDD seems to be associated with global HcV atrophy. Larger longitudinal follow-up studies designed to analyze the influence of sociodemographic variables on this relationship are required to yield better evidence about this topic.

Cited by 132 publications

References 48 publications

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

Chronic chemogenetic activation of forebrain excitatory neurons in postnatal life evokes long-lasting changes in mood-related behavior

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

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