Hippocampal volume, memory, and cortisol status in major depressive disorder: Effects of treatment

Utrecht University, Utrecht, Utrecht, Netherlands
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.

Download full-text


Available from: Eric Vermetten
  • Source
    • "For example, it was reported that SSRI treatment led to a significant improvement in memory performance (i.e. immediate and delayed verbal, immediate visual, and declarative memory ) in individuals with MDD[59,60]. Moreover, two studies showed that treatment with sertraline is associated with significant improvements in psychomotor speed and executive functions[61,62]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Discussion: Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.
    Full-text · Article · Dec 2016 · BMC Medicine
  • Source
    • "Studies on the effect of psychotropic medication have produced conflicting results. One study reported an improvement in verbal memory in patients with major depressive disorder (MDD) who responded to a selective serotonin reuptake inhibitor (SSRI) antidepressant [21]. Another study of SSRI-responsive MDD patients found normal initial learning performance, but particular difficulties with generalisation of learning from one memory task to another [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: This study investigated differences in cognitive performance between middle-aged adults with and without a lifetime history of mood disorder features, adjusting for a range of potential confounders. Methods: Cross-sectional analysis of baseline data from the UK Biobank cohort. Adults aged 40-69 (n = 143,828) were assessed using measures of reasoning, reaction time and memory. Self-reported data on lifetime features of major depression and bipolar disorder were used to construct groups for comparison against controls. Regression models examined the association between mood disorder classification and cognitive performance, adjusting for sociodemographic, lifestyle and clinical confounders. Results: Inverse associations between lifetime history of bipolar or severe recurrent depression features and cognitive performance were attenuated or reversed after adjusting for confounders, including psychotropic medication use and current depressive symptoms. Participants with a lifetime history of single episode or moderate recurrent depression features outperformed controls to a small (but statistically significant) degree, independent of adjustment for confounders. There was a significant interaction between use of psychotropic medication and lifetime mood disorder features, with reduced cognitive performance observed in participants taking psychotropic medication. Conclusions: In this general population sample of adults in middle age, lifetime features of recurrent depression or bipolar disorder were only associated with cognitive impairment within unadjusted analyses. These findings underscore the importance of adjusting for potential confounders when investigating mood disorder-related cognitive function.
    Full-text · Article · Oct 2015 · European Psychiatry
  • Source
    • "A few studies suggest that neural volumes of major depressive disorder (MDD) patients that are medicated may differ from those who are unmedicated. In longitudinal studies following medication both no change and an increase in hippocampal volume have been reported (Frodl et al., 2008; Vythilingam et al., 2004); and an increase in dorsolateral prefrontal cortex has been reported (Smith et al., 2013 ). In casecontrol studies increased volumes of neural regions associated with medication have been reported for the body of the hippocampus (Malykhin et al., 2010), and dentate gyrus (Huang et al., 2013), but an apparent decrease in white matter volume in the left dorsolateral prefrontal cortex and left putamen (Zeng et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and other disorders. However, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed SSRIs for non-mood disorders. Here we evaluated SSRI effects on neural volumetrics in depressed and nondepressed monkeys. 42 socially-housed cynomolgus monkeys were randomized to treatment balanced on pretreatment depressive behavior and body weight. Monkeys were trained for oral administration of placebo or 20mg/kg sertraline HCl daily for 18 months and depressive and anxious behavior recorded. Volumes of neural regions of interest in depression were measured in magnetic resonance images and analyzed by 2 (depressed, nondepressed) X 2 (placebo, sertraline) ANOVA. Sertraline reduced anxiety (p=0.04) but not depressive behavior (p=0.43). Left Brodmann's Area (BA)32 was smaller in depressed than nondepressed monkeys (main effect of depression: p<0.05). Sertraline and depression status interacted to affect volumes of left anterior cingulate cortex (ACC), left BA24, right hippocampus (HC), and right anterior HC (sertraline X depression interactions: all p's < 0.05). In the Placebo group, depressed monkeys had smaller right anterior HC and left ACC than nondepressed monkeys. In nondepressed monkeys, sertraline reduced right HC volume, especially right anterior HC volume. In depressed monkeys sertraline increased left ACC volume. In nondepressed monkeys, sertraline reduced left BA24 volumes resulting in smaller BA24 volumes in nondepressed than sertraline-treated depressed monkeys. These observations suggest that SSRIs may differentially affect neural structures in depressed and nondepressed individuals. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jun 2015 · Neuropharmacology
Show more