Adrenal Gland Enlargement in Major Depression

Nemeroff, Charles B.; Krishnan, K. Ranga Rama; Reed, Deborah A.; Leder, Richard A.; Beam, Craig A.; Dunnick, N. Reed

doi:10.1001/archpsyc.1992.01820050048008

Cited by 238 publications

(91 citation statements)

References 23 publications

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“…Interestingly, although mGluR7 À/À mice have a dysregulated HPA axis, these alterations occur independent of any gross abnormality in adrenal weight with both genotypes having the same relative adrenal weight (Table 1). Increases in relative adrenal weight have been observed following chronic stress (Watanabe et al, 1992) and in major depression (Nemeroff et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Mitsukawa

Mombereau

Lötscher

et al. 2005

Neuropsychopharmacol

124

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Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety. For instance, mice with a targeted deletion of the gene for mGluR7 (mGluR7 À/À ) showed antidepressant and anxiolytic-like effects in a variety of stress-related paradigms, including the forced swim stress and the stress-induced hyperthermia tests. Deletion of mGluR7 reduces also amygdala-and hippocampus-dependent conditioned fear and aversion responses. Since the hypothalamic-pituitary-adrenal (HPA) axis regulates the stress response we investigate whether parameters of the HPA axis at the levels of selected mRNA transcripts and endocrine hormones are altered in mGluR7-deficient mice. Over all, mGluR7 À/À mice showed only moderately lower serum levels of corticosterone and ACTH compared with mGluR7 + / + mice. More strikingly however, we found strong evidence for upregulated glucocorticoid receptor (GR)-dependent feedback suppression of the HPA axis in mice with mGluR7 deficiency: (i) mRNA transcripts of GR were significantly upregulated in the hippocampus of mGluR7 À/À animals, (ii) similar increases were seen with 5-HT 1A receptor transcripts, which are thought to be directly controlled by the transcription factor GR and finally (iii) mGluR7 À/À mice showed elevated sensitivity to dexamethasone-induced suppression of serum corticosterone when compared with mGluR7 + / + animals. These results indicate that mGluR7 deficiency causes dysregulation of HPA axis parameters, which may account, at least in part, for the phenotype of mGluR7 À/À mice in animal models for anxiety and depression. In addition, we present evidence that protein levels of brain-derived neurotrophic factor are also elevated in the hippocampus of mGluR7 À/À mice, which we discuss in the context of the antidepressant-like phenotype found in those animals. We conclude that genetic ablation of mGluR7 in mice interferes at multiple sites in the neuronal circuitry and molecular pathways implicated in affective disorders.

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Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Mitsukawa

Mombereau

Lötscher

et al. 2005

Neuropsychopharmacol

124

View full text Add to dashboard Cite

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“…Using magnetic resonance imaging (MRI) and computed tomography (CT), enlargement of both the pituitary and the adrenal gland have been observed in depressed patients (Krishnan et al 1991, Axelson et al 1992, Nemeroff et al 1992, Rubin et al 1995. In laboratory animals both hyperplasia and hypertrophy of the anterior pituitary as well as adrenal gland hypertrophy have been observed after enhanced stimulation of the pituitaryadrenal axis (Gertz et al 1987, Sapolsky & Plotsky 1990).…”

Section: Clinical Findings In Depressionmentioning

confidence: 99%

The role of corticotropin-releasing factor in depression and anxiety disorders

Arborelius¹,

Mj²,

Plotsky³

et al. 1999

Journal of Endocrinology

1,239

688

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Corticotropin-releasing factor (CRF), a 41 amino acidcontaining peptide, appears to mediate not only the endocrine but also the autonomic and behavioral responses to stress. Stress, in particular early-life stress such as childhood abuse and neglect, has been associated with a higher prevalence rate of affective and anxiety disorders in adulthood. In the present review, we describe the evidence suggesting that CRF is hypersecreted from hypothalamic as well as from extrahypothalamic neurons in depression, resulting in hyperactivity of the hypothalamic-pituitaryadrenal (HPA) axis and elevations of cerebrospinal fluid (CSF) concentrations of CRF. This increase in CRF neuronal activity is also believed to mediate certain of the behavioral symptoms of depression involving sleep and appetite disturbances, reduced libido, and psychomotor changes. The hyperactivity of CRF neuronal systems appears to be a state marker for depression because HPA axis hyperactivity normalizes following successful antidepressant treatment. Similar biochemical and behavioral findings have been observed in adult rats and monkeys that have been subjected to early-life stress. In contrast, clinical studies have not revealed any consistent changes in CSF CRF concentrations in patients with anxiety disorders; however, preclinical findings strongly implicate a role for CRF in the pathophysiology of certain anxiety disorders, probably through its effects on central noradrenergic systems. The findings reviewed here support the hypothesis that CRF receptor antagonists may represent a novel class of antidepressants and/or anxiolytics.

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“…The functional abnormalities of the HPA axis in the depressed state are well described and include increased plasma cortisol concentrations [88], an enlarged adrenal cortex [89] and elevated concentrations of cortisol and corticotropin-releasing factor in the cerebrospinal fluid [90]. Cortisol levels are not suppressed following dexamethasone administration (dexamethasone suppression test [DST]) in depressed patients and this non-suppression is resolved with treatment of the psychiatric disorder.…”

Section: Endocrinological Factorsmentioning

confidence: 99%

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

et al. 2011

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Aims/hypothesis A growing body of research suggests that the prevalence of major depressive disorder (MDD) in children and youth with type 1 diabetes mellitus is significantly higher than that of youth without type 1 diabetes and is associated with increased illness severity. The objective of this article is to review the current literature on the pathophysiology of these two common diseases with respect to potential areas of overlapping biological dysfunction. Methods A search of English language articles published between 1966 and 2010 was conducted and augmented with manual review of reference lists from the identified publications. Results The evidence suggests plausible mechanisms whereby a biological relationship between type 1 diabetes and MDD may exist. These include the effects of circulating cytokines associated with autoimmune diabetes, the direct impact of insulin deficiency on neurogenesis/neurotransmitter metabolism, the effects of the chronic hyperglycaemic state, occurrence of iatrogenic hypoglycaemia and the impact of basal hyperactivity of the hypothalamic-pituitary-adrenal axis. Major depressive disorder (MDD) is highly prevalent among children and adolescents with type 1 diabetes mellitus. The prevalence of MDD among youth with type 1 diabetes (20-27%) is at least two to three times greater than the 5-8% background rate of MDD reported for non-diabetic youth [1, 2]. Early-onset MDD is severe, and in combination with diabetes (the third most common chronic disease in childhood), is associated with poorer diabetes control, increased Conclusions/interpretation

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Adrenal Gland Enlargement in Major Depression

Cited by 238 publications

References 23 publications

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

The role of corticotropin-releasing factor in depression and anxiety disorders

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

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