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:Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity (awFC)). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the 'full picture' of connectivity changes for REMs and NREMs while making for an easy intuitive approach.
| S-EPMC10826332 | biostudies-literature
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:BackgroundEarly-onset (EO) major depressive disorder (MDD) patients experience more depressive episodes and an increased risk of relapse. Thus, on a neurobiological level, adult EO patients might display brain structure and function different from adult-onset (AO) patients.MethodsA total of 103 patients (66 females) underwent magnetic resonance imaging. Structural measures of gray matter volume (GMV) and functional connectivity networks during resting state were compared between EO (≤19 years) and AO groups. Four residual major depression symptoms, mood, anxiety, insomnia, and somatic symptoms, were correlated with GMV between groups.ResultsWe found comparatively increased GMV in the EO group, namely the medial prefrontal and insular cortex, as well as the anterior hippocampus. Functional networks in EO patients showed a comparatively weaker synchronization of the left hippocampus with the adjacent amygdala, and a stronger integration with nodes in the contralateral prefrontal cortex and supramarginal gyrus. Volumetric analysis of depression symptoms associated the caudate nuclei with symptoms of insomnia, and persisting mood symptoms with the right amygdala, while finding no significant clusters for somatic and anxiety symptoms.ConclusionsThe study highlights the important role of the hippocampus and the prefrontal cortex in EO patients as part of emotion-regulation networks. Results in EO patients demonstrated subcortical volume changes irrespective of sleep and mood symptom recovery, which substantiates adolescence as a pivotal developmental phase for MDD. Longitudinal studies are needed to differentiate neural recovery trajectories while accounting for age of onset.
| S-EPMC9323432 | 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