Hypercortisolemia and hippocampal changes in depression

Axelson, David; Doraiswamy, P. Murali; McDonald, William M.; Boyko, Orest B.; Tupler, Larry A.; Patterson, Linda; Nemeroff, Charles B.; Ellinwood, Everett H.; Krishnan, K. Ranga Rama

doi:10.1016/0165-1781(93)90046-j

Cited by 242 publications

(118 citation statements)

References 14 publications

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“…The relationship between depression and hippocampal size, however, is controversial. While some MRI studies (Nurnberger et al 1994;Sheline et al 1996) reported significantly reduced hippocampal volumes in major depression, other studies found no reduction (Axelson et al 1993b;Vakili et al 2000), although depression severity and treatment response correlated with hippocampal size (Vakili et al 2000). In conclusion, there remain questions concerning the role of potential confounding variables in the previously reported MRI data in PTSD.…”

Section: Discussionmentioning

confidence: 90%

“…Alcoholism is common in PTSD (Fontanaet al 1990) and is associated with hippocampal atrophy (Laakso et al 2000). Depression is also common in PTSD (Fontana et al 1990), impairs memory performance, and has opposite effects on HPA axis function from PTSD (Axelson et al 1993a). The relationship between depression and hippocampal size, however, is controversial.…”

Section: Discussionmentioning

confidence: 99%

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Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder

Schuff

Neylan

Lenoci

et al. 2001

Biological Psychiatry

225

155

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Background-Previous magnetic resonance imaging studies of posttraumatic stress disorder reported hippocampal volume loss. The goals of this study were 1) to determine the relationship between hippocampal atrophy and posttraumatic stress disorder in the absence of alcohol abuse, and 2) to test if loss of N-acetylaspartate (a neuron marker) in the hippocampus of posttraumatic stress disorder occurs separate from atrophy. In addition, volume changes in the entorhinal cortex were also explored.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder

Schuff

Neylan

Lenoci

et al. 2001

Biological Psychiatry

225

155

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“…Recent studies using MRI imaging have indicated that elevated cortisol levels are associated with some shrinkage of the hippocampal formation and mild cognitive impairment (4,79,133,138). This will be discussed more extensively below.…”

Section: The Hippocampus and Hpa Regulationmentioning

confidence: 99%

Stress and the Aging Hippocampus

McEwen

1999

Frontiers in Neuroendocrinology

205

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The ''glucocorticoid cascade hypothesis'' of hippocampal aging has stimulated a great deal of research into the neuroendocrine aspects of aging and the role of glucocorticoids, in particular. Besides strengthening the methods for investigating the aging brain, this research has revealed that the interactions between glucocorticoids and hippocampal neurons are far more complicated than originally envisioned and involve the participation of neurotransmitter systems, particularly the excitatory amino acids, as well as calcium ions and neurotrophins. New information has provided insights into the role of early experience in determining individual differences in brain and body aging by setting the reactivity of the hypothalamopituitary-adrenal axis and the autonomic nervous system. As a result of this research and advances in neuroscience and the study of aging, we now have a far more sophisticated view of the interactions among genes, early development, and environmental influences, as well as a greater appreciation of events at the cellular and molecular levels which protect neurons, and a greater appreciation of pathways of neuronal damage and destruction. While documenting the ultimate vulnerability of the brain to stressful challenges and to the aging process, the net result of this research has highlighted the resilience of the brain and offered new hope for treatment strategies for promoting the health of the aging brain. KEY WORDS: stress; hippocampal aging; glucocorticoid cascade hypothesis. 1999 Academic Press INTRODUCTIONThe hippocampus is a particularly vulnerable and sensitive region of the brain that is also very important for declarative and spatial learning and memory (36). Hippocampal neurons are vulnerable to seizures, strokes, and head trauma, as well as responding to stressful experiences (27,92,130). At the same time they show remarkable plasticity, involving long-term synaptic potentiation and depression, dendritic remodeling, synaptic turnover, and neurogenesis in the case of the dentate gyrus (Fig 1) (17,27,92).The work of aus der Muhlen and Ockenfels (3) first drew attention to potentially toxic actions of adrenal steroids. The reported darkly stained neurons in the hippocampus of guinea pigs exposed to high levels of glucocorticoids, an observation that has been confirmed and extended to repeated stress in subsequent studies (41,100), although there are still some doubts as to whether ''dark neurons'' may be artifacts of tissue trauma (18). In 1968, we discovered receptors for adrenal steroids in hippocampus (95), and it is now known that two types of adrenal steroid receptors exist in the hippocampus and other brain regions and mediate a variety of adrenal steroid effects on excitability, neurochemistry, and structure (27). Landfield (68) and then Sapolsky (127,128) provided evidence for a role of adrenal steroids in neuronal aging in the hippocampus, leading to the formulation of the ''glucocorticoid cascade hypothesis '' (130). This hypothesis states that glucocorticoids participate in a ...

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“…Two early studies examined the hippocampusamygdala complex and found no difference in volume (Axelson et al, 1993;Coffey et al, 1993). Seven studies found a smaller hippocampus in depressed subjects compared with healthy volunteers (Bremner et al, 2000;Mervaala et al, 2000;Sheline et al, 1999Sheline et al, , 1996Steffens et al, 2000;Vythilingam et al, 2002), and two studies found no difference (Ashtari et al, 1999;Vakili et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Volumetric Analysis of the Prefrontal Cortex, Amygdala, and Hippocampus in Major Depression

Hastings

Parsey

Oquendo

et al. 2003

Neuropsychopharmacol

325

194

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Magnetic resonance imaging (MRI) studies in depressed subjects report smaller volumes of amygdala, hippocampus, inferior anterior cingulate, and the orbital prefrontal cortex (OPFC), components of the limbic-cortico-thalamic circuit. Major depression occurs more commonly in women, raising the possibility of an additional psychopathological process affecting women and not men. We sought to determine whether volumetric differences related to mood disorders are dependent on sex. Eight male and 10 female depressed subjects, meeting DSM III R criteria for a major depressive episode, and eight male and 10 female healthy volunteers had MRI scans on a 1.5 T GE Signa Advantage scanner. The regions of interest included amygdala, hippocampus, inferior anterior cingulate, and OPFC. In all analyses, regional volumes were normalized for total cerebral volume. Volumetric changes in the ROIs showed a significant sex by diagnosis interaction, indicating a different pattern of volumetric changes in depressed males compared with females relative to controls. Relative to sex-matched controls, the left inferior anterior cingulate was smaller in depressed males (23%) compared with depressed females (11%). Depressed females but not depressed males had smaller amygdala compared with controls (F-value ¼ 4.946, p ¼ 0.033). No significant volumetric differences were noted in the hippocampus or OPFC. No volumetric correlations were noted with clinical variables, depression subtypes, or a reported history of sexual or physical abuse. Sex may affect volumetric deficits in amygdala and anterior cingulate cortex in mood disorders, but no effects were found in the hippocampus or OPFC. The biology of mood disorders in females may differ in some aspects from males, and may contribute to the higher rate of depression in women.

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Hypercortisolemia and hippocampal changes in depression

Cited by 242 publications

References 14 publications

Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder

Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder

Stress and the Aging Hippocampus

Volumetric Analysis of the Prefrontal Cortex, Amygdala, and Hippocampus in Major Depression

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