Major Depression: A Role for Hippocampal Neurogenesis?

Lee, Margherita M.; Reif, Andreas; Schmitt, Angelika

doi:10.1007/7854_2012_226

Cited by 68 publications

(52 citation statements)

References 165 publications

(224 reference statements)

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“…Neurogenesis in the hippocampus of mammals may be significantly less in depressive status than in non-depressive healthy controls, which is consistent with the findings obtained from adult humans [49–50]. Neurogenesis may also be decreased in the hippocampus and apoptosis may be enhanced in cerebral cells of CMS-treated rats [30].…”

Section: Discussionsupporting

confidence: 86%

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

et al. 2015

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Major depressive disorder (MDD) is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS) as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC) of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a) may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of physiological homeostasis in humans.

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Section: Discussionsupporting

confidence: 86%

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

et al. 2015

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“…27 Interestingly, altered brain monoamine levels resulting from antidepressant treatment demonstrate a consistent reinforcing effect on adult hippocampal neurogenesis. 34 Consistent with this hypothesis, Samplin et al 35 found that males from a community sample with a history of EA had smaller hippocampal volumes. Childhood trauma was assessed by the same 28-item CTQ.…”

Section: Biological Implicationsmentioning

confidence: 91%

Childhood trauma and dimensions of depression: a specific association with the cognitive domain

Vares

Salum

Spanemberg

et al. 2015

Rev. Bras. Psiquiatr.

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Objective: To investigate associations between a history of childhood trauma and dimensions of depression in a sample of clinically depressed patients. Methods: A sample of 217 patients from a mood-disorder outpatient unit was investigated with the Beck Depression Inventory, the Hamilton Depression Rating Scale, the CORE Assessment of Psychomotor Change, and the Childhood Trauma Questionnaire. A previous latent model identifying six depressive dimensions was used for analysis. Path analysis and Multiple Indicators Multiple Causes (MIMIC) models were used to investigate associations between general childhood trauma and childhood maltreatment modalities (emotional, sexual, and physical abuse; emotional and physical neglect) with dimensions of depression (sexual, cognition, insomnia, appetite, non-interactiveness/ retardation, and agitation). Results: The overall childhood trauma index was uniquely associated with cognitive aspects of depression, but not with any other depressive dimension. An investigation of childhood maltreatment modalities revealed that emotional abuse was consistently associated with depression severity in the cognitive dimension. Conclusion: Childhood trauma, and specifically emotional abuse, could be significant risk factors for the subsequent development of cognitive symptoms of major depression. These influences might be specific to this depressive dimension and not found in any other dimension, which might have conceptual and therapeutic implications for clinicians and researchers alike.

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“…In humans, aberrant adult neurogenesis has been linked to epilepsy (Hattiangady et al, 2004; Jessberger et al, 2007), intellectual disability (Luo et al, 2010; Scotto-Lomassese et al, 2011), affective disorders (Samuels and Hen, 2011; Valvezan and Klein, 2012; Petrik et al, 2012; Lee et al, 2013), anxiety disorders (Revest et al, 2009), and, especially, schizophrenia (Reif et al, 2007; Toro and Deakin, 2007; Inta et al, 2011). We focus on schizophrenia, as it has been subject to the most-intensive study, and, importantly, hippocampal and olfactory function are notably compromised in schizophrenic patients, as described below.…”

Section: Potential Disadvantages Of Adult Neurogenesismentioning

confidence: 99%

The adaptive significance of adult neurogenesis: an integrative approach

Konefal¹,

Elliot²,

Crespi³

2013

Front. Neuroanat.

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Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts.

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Major Depression: A Role for Hippocampal Neurogenesis?

Cited by 68 publications

References 165 publications

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

Childhood trauma and dimensions of depression: a specific association with the cognitive domain

The adaptive significance of adult neurogenesis: an integrative approach

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