Glucocorticoids, depression, and mood disorders: structural remodeling in the brain

McEwen, Bruce S.

doi:10.1016/j.metabol.2005.01.008

Cited by 626 publications

(455 citation statements)

References 36 publications

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“…Beyond its long-established functional role in stress-induced endocrine, autonomic, and behavioral responses via action at the hypothalamic-pituitary-adrenal (HPA) axis, CRH supports anxiety, via widespread CRHcontaining neurons at extrahypothalamic sites, in particular in limbic structures (Makino et al 1994a;1994b). Dysregulation of CRH activity has been linked to anxiety and mood disorders (Carroll et al 1976;McEwen 2005;Shea et al 2005) and acute and chronic treatment with CRH in rodents results in potentiation of anxiety-like responses in a number of behavioral assays of anxiety (Adamec and McKay 1993;Diamant et al 1992;Sherman and Kalin 1988). In contrast, CRH antagonists abolish stress-induced potentiation of anxiety (Korte and De Boer 2003).…”

Section: Preclinical Evidence For Dissociated Neural Systems Of Fear mentioning

confidence: 99%

Models and mechanisms of anxiety: evidence from startle studies

2007

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Rationale-Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety).Objective-To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety.Results-The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to nonphobic anxiety disorders.Conclusions-Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.

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Section: Preclinical Evidence For Dissociated Neural Systems Of Fear mentioning

confidence: 99%

Models and mechanisms of anxiety: evidence from startle studies

2007

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“…The prefrontal cortex atrophies and the amygdala increases in size during acute stress and atrophies during extended periods of stress, thus suggesting multiple routes by which stress can disrupt the mood network. 56 One interpretation of the dementia prodrome hypothesis is that the neural networks underlying mood partially overlaps with areas subserving cognition, which are susceptible to subtle and/or cumulative disruption. 46 …”

Section: Current Hypotheses For Biological Mechanisms Promoting Lldmentioning

confidence: 99%

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

McKinney

Sibille

2013

The American Journal of Geriatric Psychiatry

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The phenomenological diagnosis of depression is successful in increasing diagnostic reliability, but it is a classification scheme without biological bases. One subtype of depression for which evidence suggests a unique biological basis is late-life depression (LLD), with first onset of symptoms after the age of 65. LLD is common and poses a significant burden on affected individuals, caretakers, and society. The pathophysiology of LLD includes disruptions of the neural network underlying mood, which can be conceptualized as the result of dysfunction in multiple underlying biological processes. Here, we briefly review current LLD hypotheses and then describe the characteristics of molecular brain aging and their overlap with disease processes. Further, we propose a new hypothesis for LLD, the Age-by-Disease Interaction hypothesis, which posits that the clinical presentation of LLD is the integrated output of specific biological processes that are pushed in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, hence leading the brain to a physiological state that is more susceptible to LLD, since additional pushes by genetic, environmental and biochemical factors may now be sufficient to generate dysfunctional states that produce depressive symptoms. We put our propositions together into a decanalization model to aid in illustrating how age-related biological changes of the brain can shift the repertoire of available functional states in a pro-depression direction, and how additional factors can readily lead the system into distinct and stable maladaptive phenotypes, including LLD. This model brings together basic research on neuropsychiatric and neurodegenerative diseases more closely with the investigation of normal aging. Specifically, identifying biological processes affected during normal aging may inform the development of new interventions for the prevention and treatment of LLD.

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“…Interestingly, stress, often precipitating depressive episodes, has been shown to display opposite effects on BDNF and NT-3 expression in the hippocampus of rodents: BDNF was down-regulated, while expression of NT-3 was up-regulated (Smith 1996). The altered expression of neurotrophins might be related to the observation that chronic stress leads to atrophy in hippocampal CA3 neurons (McEwen 2005). These stress effects have been suggested to be related to the development of depression and might be antagonized by application of various antidepressants.…”

Section: Paroxetine-induced Effects On Neurotrophic Factorsmentioning

confidence: 99%

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

et al. 2008

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Introduction Monoamine-based antidepressants inhibit neurotransmitter reuptake within short time. However, it commonly takes several weeks until clinical symptoms start to resolve-indicating the involvement of effects distant from reuptake inhibition. Objective To unravel other mechanisms involved in drug action, a "reverse" pharmacological approach was applied to determine antidepressant-induced alterations of hippocampal gene expression. Materials and methodsThe behavioral response to longterm paroxetine administration of male DBA/2Ola mice was assessed by the forced swim test (FST), the modified hole board (mHB), and the dark/light box. Hippocampi of test-naive mice were dissected, and changes in gene expression by paroxetine treatment were investigated by means of microarray technology. Results and discussion Robust effects of paroxetine on passive stress-coping behavior in the FST were observed. Furthermore, anxiolytic properties of long-term antidepressant treatment could be identified in DBA mice in both, the mHB and dark/light box. Analysis of microarray results revealed a list of 60 genes differentially regulated by chronic paroxetine treatment. Preproenkephalin 1 and inhibin beta-A showed the highest level of transcriptional change. Furthermore, a number of candidates involved in neuroplasticity/neurogenesis emerged (e.g., Bdnf, Gfap, Vim, Sox11, Egr1, Stat3). Seven selected candidates were confirmed by in situ hybridization. Additional immunofluorescence colocalization studies of GFAP and vimentin showed more positive cells to be detected in long-term paroxetine-treated DBA mice. Conclusion Candidate genes identified in the current study using a mouse strain validated for its responsiveness to long-term paroxetine treatment add, in our opinion, to unraveling the mechanism of action of paroxetine as a representative for SSRIs.

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Glucocorticoids, depression, and mood disorders: structural remodeling in the brain

Cited by 626 publications

References 36 publications

Models and mechanisms of anxiety: evidence from startle studies

Models and mechanisms of anxiety: evidence from startle studies

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

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