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      Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder

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          Abstract

          The acute treatment duration for major depressive disorder (MDD) is 8 weeks or more. Treatment of patients with MDD without predictors of treatment response and future recurrence presents challenges and clinical problems to patients and physicians. Recently, many neuroimaging studies have been published on biomarkers for treatment response and recurrence of MDD using various methods such as brain volumetric magnetic resonance imaging (MRI), functional MRI (resting-state and affective tasks), diffusion tensor imaging, magnetic resonance spectroscopy, near-infrared spectroscopy, and molecular imaging (i.e., positron emission tomography and single photon emission computed tomography). The results have been inconsistent, and we hypothesize that this could be due to small sample size; different study design, including eligibility criteria; and differences in the imaging and analysis techniques. In the future, we suggest a more sophisticated research design, larger sample size, and a more comprehensive integration including genetics to establish biomarkers for the prediction of treatment response and recurrence of MDD.

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          Most cited references96

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          The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research?

          Major depressive disorder (MDD) has until recently been conceptualized as an episodic disorder associated with 'chemical imbalances' but no permanent brain changes. Evidence has emerged in the past decade that MDD is associated with small hippocampal volumes. This paper reviews the clinical and biological correlates of small hippocampal volumes based on literature searches of PubMed and EMBASE and discusses the ways in which these data force a re-conceptualization of MDD. Preclinical data describe the molecular and cellular effects of chronic stress and antidepressant treatment on the hippocampus, providing plausible mechanisms through which MDD might be associated with small hippocampal volumes. Small hippocampal volumes are associated with poor clinical outcome and may be a mechanism through which MDD appears to be a risk factor for Alzheimer's disease. The pathways through which stress may be linked to MDD, the emergence of chronicity or treatment resistance in MDD and the association between MDD and memory problems may be at least partially understood by dissecting the association with depression and changes in the hippocampus. MDD must be re-conceived as a complex illness, associated with persistent morphological brain changes that are detectable before illness onset and which may be modified by clinical and treatment variables.
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            Hippocampal volume reduction in major depression.

            Elevated levels of glucocorticoids in depression have been hypothesized to be associated with damage to the hippocampus, a brain area involved in learning and memory. The purpose of this study was to measure hippocampal volume in patients with depression. Magnetic resonance imaging was used to measure the volume of the hippocampus in 16 patients with major depression in remission and 16 case-matched nondepressed comparison subjects. Patients with depression had a statistically significant 19% smaller left hippocampal volume than comparison subjects, without smaller volumes of comparison regions (amygdala, caudate, frontal lobe, and temporal lobe) or whole brain volume. The findings were significant after brain size, alcohol exposure, age, and education were controlled for. These findings are consistent with smaller left hippocampal volume in depression.
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              Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy.

              Functional imaging studies of major depressive disorder demonstrate response-specific regional changes following various modes of antidepressant treatment. To examine changes associated with cognitive behavior therapy (CBT). Brain changes underlying response to CBT were examined using resting-state fluorine-18-labeled deoxyglucose positron emission tomography. Seventeen unmedicated, unipolar depressed outpatients (mean +/- SD age, 41 +/- 9 years; mean +/- SD initial 17-item Hamilton Depression Rating Scale score, 20 +/- 3) were scanned before and after a 15- to 20-session course of outpatient CBT. Whole-brain, voxel-based methods were used to assess response-specific CBT effects. A post hoc comparison to an independent group of 13 paroxetine-treated responders was also performed to interpret the specificity of identified CBT effects. A full course of CBT resulted in significant clinical improvement in the 14 study completers (mean +/- SD posttreatment Hamilton Depression Rating Scale score of 6.7 +/- 4). Treatment response was associated with significant metabolic changes: increases in hippocampus and dorsal cingulate (Brodmann area [BA] 24) and decreases in dorsal (BA 9/46), ventral (BA 47/11), and medial (BA 9/10/11) frontal cortex. This pattern is distinct from that seen with paroxetine-facilitated clinical recovery where prefrontal increases and hippocampal and subgenual cingulate decreases were seen. Like other antidepressant treatments, CBT seems to affect clinical recovery by modulating the functioning of specific sites in limbic and cortical regions. Unique directional changes in frontal cortex, cingulate, and hippocampus with CBT relative to paroxetine may reflect modality-specific effects with implications for understanding mechanisms underlying different treatment strategies.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                20 March 2020
                March 2020
                : 21
                : 6
                : 2148
                Affiliations
                Department of Psychiatry, Gil Medical Center and Gachon University College of Medicine, Incheon 21565, Korea; arztin01@ 123456hanmail.net
                Author notes
                [* ]Correspondence: kangsg@ 123456gachon.ac.kr
                Author information
                https://orcid.org/0000-0003-4933-0433
                Article
                ijms-21-02148
                10.3390/ijms21062148
                7139562
                32245086
                e0b159ee-d02f-4284-8328-08b0e573856f
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 February 2020
                : 19 March 2020
                Categories
                Review

                Molecular biology
                biomarker,major depressive disorder,genetics,neuroimaging,recurrence,treatment response

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