Exploring brain connectivity changes in major depressive disorder using functional-structural data fusion: A CAN-BIND-1 study.
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ABSTRACT:
SUBMITTER: Ayyash S
PROVIDER: S-EPMC8449113 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Depression is a mental disorder characterized by low mood and anhedonia that involves abnormalities in multiple brain regions and networks. Epidemiological studies demonstrated that depression has become one of the most important diseases affecting human health and longevity. The pathogenesis of the disease has not been fully elucidated. The clinical effect of treatment is not satisfactory in many cases. Neuroimaging studies have provided rich and valuable evidence that psychological symptoms and behavioral deficits in patients with depression are closely related to structural and functional abnormalities in specific areas of the brain. There were morphological differences in several brain regions, including the frontal lobe, temporal lobe, and limbic system, in people with depression compared to healthy people. In addition, people with depression also had abnormal functional connectivity to the default mode network, the central executive network, and the salience network. These findings provide an opportunity to re-understand the biological mechanisms of depression. In the future, magnetic resonance imaging (MRI) may serve as an important auxiliary tool for psychiatrists in the process of early and accurate diagnosis of depression and finding the appropriate treatment target for each patient to optimize clinical response.
| S-EPMC6886485 | biostudies-literature
Project description:BackgroundAbnormalities of the striatum and frontal cortex have been reported consistently in studies of neural structure and function in major depressive disorder (MDD). Despite speculation that compromised connectivity between these regions may underlie symptoms of MDD, little work has investigated the integrity of frontostriatal circuits in this disorder.MethodsFunctional magnetic resonance images were acquired from 21 currently depressed and 19 never-disordered women during wakeful rest. Using four predefined striatal regions-of-interest, seed-to-whole brain correlations were computed and compared between groups.ResultsCompared to controls, depressed participants exhibited attenuated functional connectivity between the ventral striatum and both ventromedial prefrontal cortex and subgenual anterior cingulate cortex. Depressed participants also exhibited stronger connectivity between the dorsal caudate and dorsal prefrontal cortex, which was positively correlated with severity of the disorder.ConclusionsDepressed individuals are characterized by aberrant connectivity in frontostriatal circuits that are posited to support affective and cognitive processing. Further research is required to examine more explicitly the link between patterns of disrupted connectivity and specific symptoms of depression, and the extent to which these patterns precede the onset of depression and normalize with recovery from depressive illness.
| S-EPMC3384258 | biostudies-literature
Project description:ObjectivesPrevious studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response.MethodsIndividuals in a major depressive episode received escitalopram treatment (10-20 mg/d) for 8 weeks. Depression severity was assessed at baseline and at weeks 8 and 16 using the Montgomery-Asberg Depression Rating Scale (MADRS). Response to treatment was characterized by a significant reduction in the MADRS (≥50%). Nonresponders received adjunctive aripiprazole treatment (2-10 mg/d) for a further 8 weeks. The brain-predicted age difference (brain-PAD) at baseline was determined using machine learning methods trained on 3377 healthy individuals from seven publicly available datasets. The model used features from all brain regions extracted from structural magnetic resonance imaging data.ResultsBrain-PAD was significantly higher in older MDD participants compared to younger MDD participants [t(147.35) = -2.35, p < 0.03]. BMI was significantly associated with brain-PAD in the MDD group [r(155) = 0.19, p < 0.03]. Response to treatment was not significantly associated with brain-PAD.ConclusionWe found an elevated brain age gap in older individuals with MDD. Brain-PAD was not associated with overall treatment response to escitalopram monotherapy or escitalopram plus adjunctive aripiprazole.
| S-EPMC8556529 | biostudies-literature
Project description:BackgroundMajor depressive disorder (MDD) is an increasingly common and disabling illness. As the amygdala has been reported to have pathological involvement in mood disorders, we aimed to investigate for the first time potential changes to structural connectivity of individual amygdala subnuclei in MDD using ultra-high-field 7T diffusion magnetic resonance imaging.MethodsTwenty-four patients with MDD (11 women) and 24 age-matched healthy control participants (7 women) underwent diffusion-weighted imaging with a 1.05-mm isotropic resolution at 7T. Amygdala nuclei regions of interest were obtained through automated segmentation of 0.69-mm resolution T1-weighted images and 0.35-mm resolution T2-weighted images. Probabilistic tractography was performed on all subjects, with random seeding at each amygdala nucleus.ResultsThe right lateral, basal, central, and centrocortical amygdala nuclei exhibited significantly increased connection density to the rest of the brain, whereas the left medial nucleus demonstrated significantly lower connection density (false discovery rate p < .05). Increased connection density in the right lateral and basal nuclei was driven by the stria terminalis, and the significant difference in the right central nucleus was driven by the uncinate fasciculus. Decreased connection density at the left medial nucleus did not appear to be driven by any individual white matter tract.ConclusionsBy exploiting ultra-high-resolution magnetic resonance imaging, structural hyperconnectivity was demonstrated involving the amygdaloid nuclei in the right hemisphere in MDD. To a lesser extent, impairment of subnuclei connectivity was shown in the left hemisphere.
| S-EPMC7010542 | biostudies-literature
Project description:BackgroundCognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks.MethodsCognitive performance of n = 805 healthy and n = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength.ResultsAll cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course.ConclusionsOur study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterations may mediate the association of cognitive deficits and depression severity.
| S-EPMC10600941 | biostudies-literature
Project description:A single nucleotide polymorphism of rs1360780 in the FKBP5 gene is associated with a predisposition to developing major depressive disorder (MDD). We investigated the interactive effects of FKBP5 rs1360780 allelic variants, DNA methylation, and the diagnosis of MDD on structural changes of the entire brain. One hundred and fourteen patients with MDD and eighty-eight healthy controls underwent T1-weighted structural magnetic resonance imaging and FKBP5 rs1360780 genotyping, including DNA methylation of intron 7. We analyzed the volume of cortical and subcortical regions and cortical thickness using FreeSurfer. Significant genotype-by-diagnosis interactions were observed for volumes of the left pars triangularis, supramarginal gyrus, superior parietal lobule, right frontomarginal, and posterior midcingulate gyrus. The T allele was associated with significant volume reductions in these brain regions only in the MDD group except for the right posterior midcingulate gyrus. FKBP5 DNA methylation showed a positive correlation with the thickness of the right transverse frontopolar gyrus in the C allele homozygote group. Our findings suggest that the FKBP5 gene and its epigenetic changes could have influence on morphologic changes of several brain regions involved in emotion regulation, and that this process may be associated with the development of MDD.
| S-EPMC5309810 | biostudies-literature
Project description:Previous functional magnetic resonance imaging (fMRI) studies demonstrated an abnormally coordinated network functioning in Major Depression Disorder (MDD) during rest. The main monoamine-producing nuclei within midbrain/brainstem are functionally integrated within these specific networks. Therefore, we aimed to investigate the resting-state functional connectivity (RSFC) of these nuclei in 45 MDD patients and differences between patients receiving two different classes of antidepressant drugs. Patients showed reduced RSFC from the ventral tegmental area (VTA) to dorsal anterior cingulate cortex (dACC) and stronger RSFC to the left amygdala and dorsolateral prefrontal cortex (DLPFC). Patients treated with antidepressants influencing noradrenergic and serotonergic neurotransmission showed different RSFC from locus coeruleus to DLPFC compared to patients treated with antidepressants influencing serotonergic neurotransmission only. In the opposite contrast patients showed stronger RSFC from dorsal raphe to posterior brain regions. Enhanced VTA-RSFC to amygdala as a central region of the salience network may indicate an over-attribution of the affective salience to internally-oriented processes. Significant correlation between decreased VTA-dACC functional connectivity and the BDI-II somatic symptoms indicates an association with diminished volition and behavioral activation in MDD. The observed differences in the FC of the midbrain/brainstem nuclei between two classes of antidepressants suggest differential neural effects of SSRIs and SNRIs.
| S-EPMC5561091 | biostudies-literature
Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.
2011-10-04 | E-GEOD-19738 | biostudies-arrayexpress
Project description:Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
| S-EPMC8589647 | biostudies-literature
Project description:Single Nucleotide Polymorphic (SNP) variations of proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) have been reported to be closely associated with the major depressive disorder (MDD). However, it is unclear if proinflammatory genetic burden adversely affects the regional gray matter volume in patients with MDD. The aim of this study was to test whether rs1799724, an SNP of TNF-α, contributes to the neuroanatomical changes in MDD. In this cross-sectional study, a total of 144 MDD patients and 111 healthy controls (HC) well matched for age, sex and education were recruited from Shanghai Mental Health Center. Voxel-based morphometry (VBM) followed by graph theory based structural covariance analysis was applied to locate diagnosis x genotype interactions. Irrespective of diagnosis, individuals with the high-risk genotype (T-carriers) had reduced volume in left angular gyrus (main effect of genotype). Diagnosis x genotype interaction was exclusively localized to the visual cortex (right superior occipital gyrus). The same region also showed reduced volume in patients with MDD than HC (main effect of diagnosis), with this effect being most pronounced in patients carrying the high-risk genotype. However, neither global nor regional network of structural covariance was found to have group difference. In conclusion, a genetic variation which can increase TNF-α expression selectively affects the anatomy of the visual cortex among the depressed subjects, with no effect on the topographical organization of multiple cortical regions. This supports the notion that anatomical changes in depression are in part influenced by the genetic determinants of inflammatory activity.
| S-EPMC6181976 | biostudies-literature