Hippocampal Volume, Memory, and Cortisol Status in Major Depressive Disorder: Effects of Treatment

Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Maryland 20892-2670, USA.
Biological Psychiatry (Impact Factor: 10.26). 08/2004; 56(2):101-12. DOI: 10.1016/j.biopsych.2004.04.002
Source: PubMed


Depression has been linked to stress, memory deficits, and hypercortisolemia. However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied.
Whole hippocampal volume, performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder (MDD) and 33 healthy subjects. All measures were repeated in a subgroup (n = 22) of depressed patients after successful selective serotonin reuptake inhibitor (SSRI) treatment.
Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects, after controlling for whole brain volume, age and gender. However, depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised (WMS-R) compared with healthy subjects, without significant differences in visual memory, attention, vigilance, or distractibility. Baseline plasma or urinary free cortisol (UFC) was not related to either hippocampal volume or memory deficits. Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion.
Medication-free nonelderly depressed outpatients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume. Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients. Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume, suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes.

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Available from: Eric Vermetten, Oct 07, 2015
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    • "Studies in psychiatric patients report associations between HPA axis dysregulation and reduced HV (O'Brien et al., 2004; Swaab et al., 2005; Bremner, 2006; Karl et al., 2006). Among healthy populations, studies have revealed that smaller HV is associated with higher basal cortisol levels in young (Wolf et al., 2002; Vythilingam et al., 2004) and older adults (Lupien et al., 1998; Wolf et al., 2002; O'Hara et al., 2007; Bruehl et al., 2009; Knoops et al., 2010). However, results elsewhere show no such association in various age groups (age range: 20–70 years) (MacLullich et al., 2005; Gunduz-Bruce et al., 2007; Gold et al., 2010; Kaymak et al., 2010; Kremen et al., 2010; Mondelli et al., 2010; Collip et al., 2013). "
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    ABSTRACT: The hypothalamic pituitary adrenal axis production of the stress hormone cortisol interacts with the hippocampal formation and impacts memory function. A growing interest is to determine whether hippocampal volume (HV) predicts basal and/or reactive cortisol levels in young and older adults. Recent evidence shows that contextual features in testing environments might be stressful and inadvertently induce a stress response in young and/or older populations. This latter result suggests that variations in testing environments might influence associations between HV and cortisol levels in young and older adults. To this end, we investigated 28 healthy young adults (ages 18 to 35) and 32 healthy older adults (ages 60 to 75) in two different environments constructed to be more or less stressful for each age group (Favouring-Young versus Favouring-Old conditions). Cortisol levels were repeatedly assessed in each environment, and young and older participants underwent an anatomical magnetic resonance imaging scan for subsequent assessment of HV. Results in both age groups showed that HV was significantly associated with cortisol levels only in the unfavourable stressful testing conditions specific for each age group. This association was absent when testing environments were designed to decrease stress for each age group. These findings are fundamental in showing that unless the nature of the testing environment is taken into consideration, detected associations between HV and cortisol levels in both young and older populations might be confounded by environmental stress. © 2014 Wiley Periodicals, Inc.
    Hippocampus 12/2014; 24(12). DOI:10.1002/hipo.22341 · 4.16 Impact Factor
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    • "Moreover, drug-induced changes in appetite and energy balance may exert a detrimental effect on cognitive performance, as interferences in glucose metabolism translate into insulin resistance [135], neurotransmitters abnormal turnover, mitochondrial dysfunction and alterations in neuroplasticity [136]. Mechanistically diverse psychotropic agents exert disparate effects on the immune-inflammatory system suggesting a possible effector system mediating the antidepressant effect on cognitive performance in adults with remitted MDD are controversial [116] and future studies with larger adult and young samples as well as with a longitudinal design are warranted to elucidate their impact on cognition in MDD. "
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    ABSTRACT: Major depressive disorder (MDD) is a prevalent and recurring mental disorder often associated with high rates of non-recovery and substantial consequences on psychosocial outcome. Cognitive impairment is one of the most frequent residual symptoms of MDD. The persistence of cognitive impairment even in remitted phases of the disorder, notably in the domains of executive function and attention, suggests that it may serve as a mediational nexus between MDD and poor functional outcome, accounting for occupational and relational difficulties regardless of clinical improvement on depressive symptoms. The critical impact of cognitive deficits on psychosocial dysfunction invites clinicians to regularly screen and assess cognition across multiple domains, taking into account also clinical correlates of cognitive dysfunction in MDD. Despite the availability of several instruments for the screening and assessment of cognitive dysfunction, the lack of consensus guiding the choice of appropriate instruments increases the likelihood to underestimate cognitive dysfunction in MDD in clinical settings. On the other hand, the unsatisfactory effect of most antidepressant treatments on cognitive deficits for many individuals with MDD calls for the development of genuinely novel therapeutic agents with potential to target cognitive dysfunction. Notwithstanding the necessity of further investigations, this review indicates that neuropsychological deficits (e.g., impaired executive functions) are stable markers of MDD and underscores the need for the development of integrative and multi-modal strategies for the prevention and treatment of neuropsychological impairments in MDD.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 11/2014; 13(10). DOI:10.2174/1871527313666141130203823 · 2.63 Impact Factor
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    • "An association between higher cortisol levels and smaller hippocampal volumes has been supported from studies in healthy controls and samples with psychiatric disorders with a continuous measure of the cortisol levels over 1 day, rather than measures taken at one time of the day only (Frodl & O'Keane, 2013). Only one study in MDD investigated the association between 24-hr urinary cortisol and the hippocampus ; it failed to find a significant result in the patient's group, but it was seen in the healthy comparison group (Vythilingam et al., 2004). Although some studies with smaller sample sizes of between 20 to 40 patients did not show such an association between cortisol measures post-dexamethasone (DST) and the hippocampal volume (Frodl & O'Keane, 2013), a study in a larger sample of patients with arteriosclerosis detected associations between hippocampal volume and DST cortisol (Knoops, Gerritsen, van der Graaf, Mali, & Geerlings, 2010). "
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    ABSTRACT: Alterations of the glucocorticoid system and of hippocampal volumes have consistently been reported in patients with major depressive disorders (MDD). The aim of the present study was to investigate whether the messenger RNA (mRNA) expression of glucocorticoid inducible genes is associated with changes in the cornu ammonis (CA) and dentate gyrus subfields. Forty-three patients with MDD and 43 healthy controls were recruited and investigated with high resolution magnetic resonance imaging. Hippocampal subfields were measured using freesurfer. Measurement of whole blood mRNA expression of glucocorticoid inducible genes serum and glucocorticoid-regulated kinase 1 (SGK1), FK506 binding protein 5 (FKBP5), and glucocorticoid induced leucine zipper (GILZ) was performed. Patients with MDD had significantly smaller volumes of CA1, CA2/3, CA4/DG, and subiculum compared to healthy controls. In the regression analysis, the factor diagnosis had a significant moderating effect on the association of SGK1 and hippocampal volumes. Patients with low expression of SGK1 had significantly smaller CA2/3 and CA4/DG volumes compared to patients with high expression of SGK1 mRNA and to healthy controls with low/high expression of SGK1, respectively. Therefore, a lack of mRNA expression of glucocorticoid inducible genes in patients with MDD that seems to correspond to a blunted cortisol response is associated with smaller hippocampal CA and dentate gyrus volumes. SGK1 seems to be particularly relevant for stress-related mental disorders.
    Development and Psychopathology 11/2014; 26(4 Pt 2):1209-17. DOI:10.1017/S0954579414000972 · 4.89 Impact Factor
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