Dataset Information

Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms.

ABSTRACT: Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss, and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD.

SUBMITTER: Misaki M

PROVIDER: S-EPMC4754797 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms.

Misaki Masaya M Suzuki Hideo H Savitz Jonathan J Drevets Wayne C WC Bodurka Jerzy J

Scientific reports 20160216

Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control ...[more]

PMID: 26880358

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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.

Dataset Information

Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms.

Publications

Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms.

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