Abstract

BackgroundObsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood. In this study, we utilized magnetic resonance spectroscopy (MRS) in an effort to provide a better understanding of the role of brain gamma-aminobutyric acid (GABA) and glutamate in the pathophysiology of OCD. We hypothesized that beyond the separate effects of these neurotransmitter systems, a disruption in the balance between GABA and glutamate could be particularly relevant to OCD.MethodsWe obtained MRS measures of GABA and glutamate concentrations in the anterior cingulate cortex from 23 adult patients with OCD and 20 sex- and age-matched healthy community volunteers. Established clinical rating scales were used to assess the severities of OCD, anxiety, and depression symptoms. Statistical analysis involved the assessment of patient-control group differences in the individual measures of GABA and glutamate, as well as in the ratio of the GABA to glutamate measures. Additionally, we explored whether differences in the MRS measures existed between two subgroups of patients formed according to the severity of their OCD symptoms. Finally, we assessed the relations of demographic and clinical variables to the MRS measures.ResultsPatients with OCD displayed a higher estimated GABA level and a higher GABA to glutamate ratio than healthy participants, but no significant group differences were observed in the measure of glutamate. The MRS measures did not vary by subgroup and showed no correlations with demographic and clinical variables.ConclusionsThese results indicate that GABA abnormalities within the anterior cingulate cortex contribute to the pathophysiology of OCD. The results fail to provide evidence that glutamate abnormalities alone are involved in adult OCD. Yet, it seems that a disruption in the balance between glutamate and GABA neurotransmission may have a particularly important role to play in OCD pathophysiology.

Highlights

  • Obsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood

  • Studies using magnetic resonance spectroscopy (MRS) have documented abnormalities in the levels of neurotransmitter-related metabolites in several distinct brain areas of patients with OCD [7], including decreased glutamate-glutamine (Glx) concentrations in the anterior cingulate cortex (ACC) [8] and increased gammaaminobutyric (GABA) concentrations in the medial prefrontal cortex [9]. These clinical studies have contributed to the hypothesis that dysfunctions within cortico-striatothalamo-cortical (CSTC) brain circuitry are fundamental to the pathophysiology of OCD

  • The present results indicate that gamma-aminobutyric acid (GABA) abnormalities within the CSTC circuit are linked to OCD pathophysiology

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Summary

Introduction

Obsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood. Studies using magnetic resonance spectroscopy (MRS) have documented abnormalities in the levels of neurotransmitter-related metabolites in several distinct brain areas of patients with OCD [7], including decreased glutamate-glutamine (Glx) concentrations in the anterior cingulate cortex (ACC) [8] and increased gammaaminobutyric (GABA) concentrations in the medial prefrontal cortex [9]. These clinical studies have contributed to the hypothesis that dysfunctions within cortico-striatothalamo-cortical (CSTC) brain circuitry are fundamental to the pathophysiology of OCD

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