Corticosteroid status influences the volume of the rat cingulate cortex - a magnetic resonance imaging study.

Neuroscience Group, Life and Health Sciences Research Institute (ICVS), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Journal of Psychiatric Research (Impact Factor: 4.09). 10/2005; 39(5):451-60. DOI: 10.1016/j.jpsychires.2005.01.003
Source: PubMed

ABSTRACT Imbalances in the corticosteroid milieu result in reductions in hippocampal volume in humans and experimental rodents. The functional correlates of these changes include deficits in cognitive performance and regulation of the hypothalamic-pituitary-adrenal axis. Since other limbic structures which are intricately connected with the hippocampal formation, also play an important role in behavioural and neuroendocrine functions, we here used magnetic resonance imaging (MRI) to analyse how two of these areas, the anterior cingulate and retrosplenial cortex, respond to chronic alterations of adrenocortical status: hypocortisolism (induced by adrenalectomy, ADX), normocortisolism (ADX with low-dose corticosterone replacement), and hypercortisolism (ADX with high-dose dexamethasone supplementation). Hypercortisolism was associated with a significant reduction in the volume (absolute and normalized) of the left anterior cingulate gyrus as measured by MRI and confirmed using classical histological methods; a similar trend was observed in the right anterior cingulate region. In contrast, hypercortisolism did not influence the volume of the adjacent retrosplenial cortex. The volumes of the anterior cingulate gyrus and retrosplenial cortex were unaffected by the absence of adrenocortical hormones. These findings are the first to suggest that corticosteroid influences on the structure of the limbic system extend beyond the hippocampal formation, i.e., to fronto-limbic areas also.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective:Antisocial personality disorder (ASPD) and schizophrenia, as well as childhood abuse, are associated with violent behaviour and show marked volumetric reduction in the anterior cingulate (AC), a brain region implicated in regulation of violence through its involvement in decision making, empathy, impulse control, and emotion regulation. The present study examined, for the first time to the authors' knowledge, the grey matter volume of the AC in relation to seriously violent behaviour and childhood psychosocial deprivation (including physical and sexual abuse) in the context of a mental disorder (schizophrenia or ASPD).Methods:Fifty-seven men [14 with ASPD and a history of serious violence; 13 with schizophrenia and a history of serious violence (VSZ); 15 with schizophrenia without a violence history (SZ); 15 nonviolent healthy participants] underwent whole-brain magnetic resonance imaging and were rated on the presence of physical abuse, sexual abuse, neglect, extreme poverty, foster home placement, criminal parent, severe family conflict, and broken home (collectively 'psychosocial deprivation'). Stereological volumetric ratings of the AC were examined for group differences and their association with childhood psychosocial deprivation.Results:A higher proportion of ASPD and VSZ patients had suffered psychosocial deprivation as children, in particular severe physical abuse, relative to SZ patients and healthy participants. ASPD and VSZ, but not SZ, patients had significantly lower AC volume relative to healthy participants. AC volumes correlated negatively with (total) psychosocial deprivation as well as physical and sexual abuse ratings. Group differences in AC volume became nonsignificant when psychosocial deprivation ratings were covaried for.Conclusions:Violent mentally disordered individuals with ASPD or schizophrenia suffer from a significant AC volume loss and this deficit, at least in part, is explained by their histories of stressful childhood experiences. Current and future therapies aiming to reduce violence in such populations would benefit by attending to biological (and other) correlates of childhood abuse.
    Australian and New Zealand Journal of Psychiatry 11/2013; · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activation of the hypothalamo-pituitary-adrenal (HPA) axis plays a vital role in promoting adaptation during acute stress, but adverse effects of chronic stress may result from overactivity of this system. Recent evidence highlights a subdivision of GABAergic neurons within anterior bed nuclei of the stria terminalis (aBST) that integrates and relays inhibitory influences to HPA-effector neurons in paraventricular hypothalamus during acute stress, notably from medial prefrontal [prelimbic (PL)] and hippocampal [ventral subiculum (vSUB)] cortical fields. Here we localize the site and candidate mechanism of neuroplasticity within upstream regions of this inhibitory network after chronic variable stress (CVS). Rats bearing retrograde tracer injections in aBST underwent CVS for 14 d. Retrogradely labeled and unlabeled neurons in vSUB and PL were selected for intracellular dye filling, followed by three-dimensional imaging and analysis of dendritic arborization and spine morphometry. Whereas PL neurons displayed decreases in dendritic branching and spine density after CVS, aBST-projecting cells showed a selective loss of mature mushroom-shaped spines. In a follow-up experiment, CVS-treated and control rats were exposed to a novel restraint challenge for assay of HPA activation and engagement of aBST-projecting cortical regions. CVS animals showed enhanced HPA output and decreased Fos activation in aBST-projecting PL neurons compared with acutely stressed controls. In contrast, vSUB failed to show any significant differences in structural plasticity or functional activation patterns after CVS. These findings define a mechanism whereby synaptic destabilization in the PL → aBST pathway may dampen its ability to impart inhibitory control over the HPA axis after chronic stress exposure.
    Journal of Neuroscience 09/2013; 33(36):14379-91. · 6.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in a sample of patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction, and clinical severity. A cross-sectional, case control study. In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, anterior cingulate cortex) and in the whole brain were examined, using 3T Magnetic Resonance Imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome Severity Index. Compared to controls, patients had smaller grey matter volumes of areas in the anterior cingulate cortex (on average 14%, P<0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P<0.05). As expected, patients with remitted CD reported more depressive symptoms (P=0.005), more anxiety (P=0.003), more social phobia (P=0.034), more apathy (P=0.002) and more cognitive failure (P=0.023) compared to controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity. Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.
    European Journal of Endocrinology 09/2013; · 3.14 Impact Factor

Full-text (2 Sources)

Available from
May 21, 2014