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Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/1H MRS Study.

ABSTRACT: Depression is a commonly occurring symptom in obsessive-compulsive disorder (OCD), and is associated with worse functional impairment, poorer quality of life, and poorer treatment response. Understanding the underlying neurochemical and connectivity-based brain mechanisms of this important symptom domain in OCD is necessary for development of novel, more globally effective treatments. To investigate biopsychological mechanisms of comorbid depression in OCD, we examined effective connectivity and neurochemical signatures in the pregenual anterior cingulate cortex (pACC), a structure known to be involved in both OCD and depression. Resting-state functional magnetic resonance imaging (fMRI) and 1H magnetic resonance spectroscopy (MRS) data were obtained from participants with OCD (n=49) and healthy individuals of equivalent age and sex (n=25). Granger causality-based effective (directed) connectivity was used to define causal networks involving the right and left pACC. The interplay between fMRI connectivity, 1H MRS and clinical data was explored by applying moderation and mediation analyses. We found that the causal influence of the right dorsal anterior midcingulate cortex (daMCC) on the right pACC was significantly lower in the OCD group and showed significant correlation with depressive symptom severity in the OCD group. Lower and moderate levels of glutamate (Glu) in the right pACC significantly moderated the interaction between right daMCC-pACC connectivity and depression severity. Our results suggest a biochemical-connectivity-psychological model of pACC dysfunction contributing to depression in OCD, particularly involving intracingulate connectivity and glutamate levels in the pACC. These findings have implications for potential molecular and network targets for treatment of this multi-faceted psychiatric condition.

SUBMITTER: Tadayonnejad R

PROVIDER: S-EPMC5854805 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/<sup>1</sup>H MRS Study.

Tadayonnejad Reza R Deshpande Rangaprakash R Ajilore Olusola O Moody Teena T Morfini Francesca F Ly Ronald R O'Neill Joseph J Feusner Jamie D JD

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20171020 5

Depression is a commonly occurring symptom in obsessive-compulsive disorder (OCD), and is associated with worse functional impairment, poorer quality of life, and poorer treatment response. Understanding the underlying neurochemical and connectivity-based brain mechanisms of this important symptom domain in OCD is necessary for development of novel, more globally effective treatments. To investigate biopsychological mechanisms of comorbid depression in OCD, we examined effective connectivity and ...[more]

PMID: 29052616

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Project description:Background:The anterior cingulate gyrus is involved in the extinction of conditioned fear responses and is implicated in the pathophysiology of posttraumatic stress disorder. The expression of N-acetylaspartate and choline may be altered in the anterior cingulate gyri of children and adolescents with posttraumatic stress disorder. Methods:We conducted a proton magnetic resonance spectroscopy study, longitudinally investigating N-acetylaspartate/creatine and choline/creatine ratios in the anterior cingulate gyri of children and adolescents, aged from 8 to 12 years, who had been exposed to various forms of violence or were non-trauma control. Based on baseline posttraumatic stress symptoms ("sub-clinical"), participants were divided into two groups: posttraumatic stress (n?=?19) and control (n?=?19). Proton magnetic resonance spectroscopy scans were repeated a year later in trauma exposed participants. Trauma assessments included the Childhood Trauma Questionnaire. Results:Exploratory analyses revealed a significant negative correlation between follow-up anterior cingulate gyrus N-acetylaspartate/creatine and Childhood Trauma Questionnaire scores in posttraumatic stress (r?=?-0.62, p?=?0.01) but not control group (r?=?0.16, p?=?0.66). However, we found no significant differences in anterior cingulate gyrus N-acetylaspartate/creatine or choline/creatine between posttraumatic stress and control. In addition, there were no significant effects of time, group, or time-by-group interactions. Conclusions:In this pediatric population, anterior cingulate gyrus N-acetylaspartate/creatine and choline/creatine were not affected by posttraumatic stress and on average these metabolites remained stable over time. However, the study provided intriguing preliminary evidence revealing that participants suffering from posttraumatic stress at baseline have shown, a year later, reduced anterior cingulate gyrus N-acetylaspartate/creatine among those with high trauma severity. This pilot evidence warrants replication in future studies to confirm these findings and to determine the longitudinal effects and interactions between childhood posttraumatic stress and trauma.

Dataset Information

Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/1H MRS Study.

Publications

Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/<sup>1</sup>H MRS Study.

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