McKinnon MCM, Yucel K, Nazarov A, MacQueen GM. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci 34: 41-54

Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Journal of psychiatry & neuroscience: JPN (Impact Factor: 5.86). 02/2009; 34(1):41-54.
Source: PubMed


Some, although not all, studies report small hippocampal volume in patients with major depressive disorder (MDD) relative to healthy controls. Here, we explore the contribution of key demographic and clinical variables to this difference.
We used meta-analytic techniques to provide an updated analysis of data from 32 magnetic resonance imaging studies of hippocampal volume in patients with MDD.
Our analysis confirmed the difference in hippocampal volume, but only among patients with MDD whose duration of illness was longer than 2 years or who had more than 1 disease episode. We found no such effect in studies that included patients who did not fit these criteria. The effect was limited to children and middle-aged or older adults. Analyzed collectively, studies including young adult patients showed equivalent hippocampal volumes across MDD patients and controls, a result that may be attributable to a reduced burden of illness in this population. Age at onset of disease, severity of depression at the time of scanning, sex and slice thickness did not contribute to differences in hippocampal volume between patients with MDD and controls.
The small size of many of the clinical and demographic subgroups may have limited statistical power to detect between-group differences.
Although all studies were cross-sectional, our results suggest that hippocampal volume reductions generally occur after disease onset in patients with MDD. These findings have implications for the timing of clinical interventions aimed at reducing the impact of MDD on neuronal structure and function.

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Available from: Anthony Nazarov
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    • "Based on the suggestion that global hippocampal volume loss is associated with illness burden-related parameters including duration of illness, number of depressive episodes, age at onset of illness, severity of illness (McKinnon et al., 2009), one study with subfield analysis revealed that reduced volume of subiculum was associated with multiple depressive episodes (Wisse et al., 2015). "
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    ABSTRACT: Background Hippocampal volume loss is known as the best-replicated finding of structural brain imaging studies on major depressive disorder (MDD). Several evidences suggest localized mechanisms of hippocampal neuroplasticity lead the brain imaging studies on the hippocampus and MDD to perform analyses in the subfield level. The aim of this study was to investigate the differences in total and subfield hippocampal volumes, between medication-naïve female MDD patients and healthy controls, through automated segmentation and volumetric methods. Methods Twenty medication-naïve female patients diagnosed with MDD and 21 age-matched healthy controls, underwent T1-weighted structural magnetic resonance scanning. Total volumes of both hippocampi and subfield regions were calculated by the automated procedure for volumetric measures implemented in FreeSurfer and automated segmentation method by Van Leemput et al. Results We observed patients to have significantly smaller volumes of the left hippocampus, subiculum, cornu ammonis 2–3, cornu ammonis 4-dentate gyrus, and right subiculum compared to healthy controls. There were no significant predictors for these subfield region volumes among the illness burden-related parameters including duration of illness, number of depressive episodes, severity of depressive symptoms and memory performances. Limitations Our findings relied on the data of only female participants. Conclusions We found significant volume reductions in several hippocampal subfield regions in medication-naïve female MDD patients. Our results are consistent with neurobiological evidences on hippocampal neuroplasticity in MDD, and replicate previous findings that suggest morphologic changes of hippocampal subfields in MDD patients.
    Full-text · Article · Apr 2016 · Journal of Affective Disorders
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    • "Neuroimaging studies consistently reveal smaller hippocampal volume in MDD (Sheline et al., 1996; Bremner et al., 2000; Lorenzetti et al., 2009; Kempton et al., 2011; Brown et al., 2014; Schmaal et al., 2015). A meta-analysis of 32 magnetic resonance imaging (MRI) studies suggests about a 4 percent smaller left hippocampal volume in patients with a history of multiple episodes of depression or duration of illness exceeding 2 years (McKinnon et al., 2009). Our group recently published a stereological assessment of the volume of the postmortem hippocampus in chronic/recurrent depression and noted that total volume was decreased with increasing duration of illness (Cobb et al., 2013). "
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    ABSTRACT: Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with major depressive disorder and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels.
    Full-text · Article · Dec 2015 · Neuroscience
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    • "Third, we searched the Internet Volume Brain Database for studies of normal subjects in which male and female HCVs were reported separately. Fourth, we hand-searched all primary studies cited in ten prior meta-analyses of hippocampal volume not related to sex differences (Adriano et al., 2012; Fusar-Poli et al., 2012; McKinnon et al., 2009; Molendijk et al., 2012; Pedraza et al., 2004; Ruocco et al., 2012; Shi et al., 2009; Smith, 2005; Videbech and Ravnkilde, 2004; Woon and Hedges, 2011). These four searches yielded 2224 citations from which we were able to identify 88 initial studies that reported HCV measurements (mean + SD) separately for age-matched samples of healthy males and females (Fig. 1). "

    Full-text · Dataset · Sep 2015
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