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Thalamo-Habenular Connection Differences Between Patients With Major Depressive Disorder and Normal Controls.

ABSTRACT: Background: The thalamus and habenula are thought to be key brain regions in the etiology of major depressive disorder (MDD); however, few studies have investigated the structural connection between them. We compared the number of white matter tracts between the thalamus and habenula between patient with MDD and normal controls (NCs). Methods: The habenula and thalamus region of interest masks were extracted from brain magnetic resonance imaging data and individual tractography analysis was performed. First, we compared the number of fiber connections from the habenula to the thalamus between the MDD (n = 34) and NC (n = 37) groups and also compared hemispherical differences to investigate possible asymmetries. Results: There was a significant difference in the number of tracts in the right habenula-left mediodorsal thalamus pair between the two groups. For hemispherical fiber connections, the waytotal ratio of the right ipsilateral tract between the thalamus and habenula was significantly higher than that of the left ipsilateral tract in both groups. Conclusion: The number of right habenula-left mediodorsal thalamus tracts was higher in patients with MDD than in NCs. These results indicate that MDD is related to the disintegration of the left thalamus-right habenula tract function with an increased number of tracts as a compensational mechanism.

SUBMITTER: Cho SE

PROVIDER: S-EPMC8440934 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:BackgroundMajor depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been hypothesized to be involved in MDD through gut-brain axis signaling. Moreover, antidepressants display antibacterial properties in the gastrointestinal tract. The aim of this study was to compare the gut microbiota and systemic inflammatory profile of young patients with MDD before and after initiation of antidepressant treatment and/or psychotherapy in comparison with a non-depressed control group (nonMDD).MethodsFecal and blood samples were collected at baseline and at follow-up after four and twelve weeks, respectively. Patients started treatment immediately after collection of the baseline samples. The gut microbiota was characterized by 16 S rRNA gene sequencing targeting the hypervariable V4 region. Plasma levels of 49 unique immune markers were assessed using Mesoscale.ResultsIn total, 27 MDD patients and 32 nonMDD controls were included in the study. The gut microbiota in the baseline samples of MDD versus nonMDD participants did not differ regarding α- or β-diversity. However, there was a higher relative abundance of the genera Ruminococcus gnavus group, and a lower relative abundance of the genera Desulfovibrio, Tyzzerella, Megamonas, Olsenella, Gordonibacter, Allisonella and Rothia in the MDD group compared to the nonMDD group. In the MDD group, there was an increase in the genera Rothia, Desulfovibrio, Gordinobacteer and Lactobacillus, while genera belonging to the Firmicutes phylum were found depleted at twelve weeks follow-up compared to baseline. In the MDD group, IL-7, IL-8 and IL-17b levels were elevated compared to the nonMDD group at baseline. Furthermore, MDI score in the MDD group was found to correlate with Bray-Curtis dissimilarity at baseline, and several inflammatory markers at both baseline and after initiation of antidepressant treatment.ConclusionSeveral bacterial taxa differed between the MDD group and the nonMDD group at baseline and changed in relative abundance during antidepressant treatment and/or psychotherapy. The MDD group was furthermore found to have a pro-inflammatory profile compared to the nonMDD group at baseline. Further studies are required to investigate the gut microbiota and pro-inflammatory profile of patients with MDD.

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Thalamo-Habenular Connection Differences Between Patients With Major Depressive Disorder and Normal Controls.

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