Neuroimaging genomic studies in major depressive disorder: A systematic review.
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ABSTRACT:
SUBMITTER: Zhang HF
PROVIDER: S-EPMC6490046 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Neuroimaging genomic studies in major depressive disorder: A systematic review.
Zhang Hui-Feng HF Mellor David D Peng Dai-Hui DH
CNS neuroscience & therapeutics 20180223 11
Genetic-neuroimaging studies could identify new potential endophenotypes of major depressive disorder (MDD). Morphological and functional alterations may be attributable to genetic factors that regulate neurogenesis and neurodegeneration. Given that the association between gene polymorphisms and brain morphology or function has varied across studies, this systematic review aims at evaluating and summarizing all available genetic-neuroimaging studies. Twenty-eight gene variants were evaluated in ...[more]
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Project description:Introduction. This paper focuses on the application of Magnetic Resonance Spectroscopy (MRS) to the study of Major Depressive Disorder (MDD) in children and adolescents. Method. A literature search using the National Institutes of Health's PubMed database was conducted to identify indexed peer-reviewed MRS studies in pediatric patients with MDD. Results. The literature search yielded 18 articles reporting original MRS data in pediatric MDD. Neurochemical alterations in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD, suggesting pathophysiologic continuity with adult MDD. Conclusions. The MRS literature in pediatric MDD is modest but growing. In studies that are methodologically comparable, the results have been consistent. Because it offers a noninvasive and repeatable measurement of relevant in vivo brain chemistry, MRS has the potential to provide insights into the pathophysiology of MDD as well as the mediators and moderators of treatment response.
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Project description:There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons. This work will be the first attempt to investigate how miR-132 dysregulation may impact covariation of multimodal brain imaging data in 81 unmedicated major depressive patients and 123 demographically-matched healthy controls, as well as in a medication-naïve subset of major depressive patients. MiR-132 values in blood (patients > controls) was used as a prior reference to guide fusion of three MRI features: fractional amplitude of low frequency fluctuations, grey matter volume, and fractional anisotropy. The multimodal components correlated with miR-132 also show significant group difference in loadings. Results indicate that (i) higher miR-132 levels in major depressive disorder are associated with both lower fractional amplitude of low frequency fluctuations and lower grey matter volume in fronto-limbic network; and (ii) the identified brain regions linked with increased miR-132 levels were also associated with poorer cognitive performance in attention and executive function. Using a data-driven, supervised-learning method, we determined that miR-132 dysregulation in major depressive disorder is associated with multi-facets of brain function and structure in fronto-limbic network (the key network for emotional regulation and memory), which deepens our understanding of how miR-132 dysregulation in major depressive disorders contribute to the loss of specific brain areas and is linked to relevant cognitive impairments.
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Project description:OBJECTIVE:Imaging studies of major depressive disorder have reported structural and functional abnormalities in a variety of spatially diverse brain regions. Quantitative meta-analyses of this literature, however, have failed to find statistically significant between-study spatial convergence, other than transdiagnostic-only effects. In the present study, the authors applied a novel multimodal meta-analytic approach to test the hypothesis that major depression exhibits spatially convergent structural and functional brain abnormalities. METHODS:This coordinate-based meta-analysis included voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies of blood flow, glucose metabolism, regional homogeneity, and amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF). Input data were grouped into three primary meta-analytic classes: gray matter atrophy, increased function, and decreased function in patients with major depression relative to healthy control subjects. In secondary meta-analyses, the data were grouped across primary categories, and in tertiary analyses, by medication status and absence of psychiatric comorbidity. Activation likelihood estimation was used for all analyses. RESULTS:A total of 92 publications reporting 152 experiments were identified, collectively representing 2,928 patients with major depressive disorder. The primary analyses detected no convergence across studies. The secondary analyses identified portions of the subgenual cingulate cortex, hippocampus, amygdala, and putamen as demonstrating convergent abnormalities. The tertiary analyses (clinical subtypes) showed improved convergence relative to the secondary analyses. CONCLUSIONS:Coordinate-based meta-analysis identified spatially convergent structural (VBM) and functional (VBP) abnormalities in major depression. The findings suggest replicable neuroimaging features associated with major depression, beyond the transdiagnostic effects reported in previous meta-analyses, and support a continued research focus on the subgenual cingulate and other selected regions' role in depression.
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