Abstract
Structural and functional neuroimaging findings suggest that disturbance of the cortico–striato–thalamo–cortical (CSTC) circuits may underlie obsessive-compulsive disorder (OCD). However, some studies with 1H-magnetic resonance spectroscopy (1H-MRS) reported altered level of N-acetylaspartate (NAA), they yielded inconsistency in direction and location of abnormality within CSTC circuits. We conducted a comprehensive literature search and a meta-analysis of 1H-MRS studies in OCD. Seventeen met the inclusion criteria for a meta-analysis. Data were separated by frontal cortex region: medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex, orbitofrontal cortex, basal ganglia and thalamus. The mean and s.d. of the NAA measure were calculated for each region. A random effects model integrating 16 separate datasets with 225 OCD patients and 233 healthy comparison subjects demonstrated that OCD patients exhibit decreased NAA levels in the frontal cortex (P=0.025), but no significant changes in the basal ganglia (P=0.770) or thalamus (P=0.466). Sensitivity analysis in an anatomically specified subgroup consisting of datasets examining the mPFC demonstrated marginally significant reduction of NAA (P=0.061). Meta-regression revealed that NAA reduction in the mPFC was positively correlated with symptom severity measured by Yale–Brown Obsessive Compulsive Scale (P=0.011). The specific reduction of NAA in the mPFC and significant relationship between neurochemical alteration in the mPFC and symptom severity indicate that the mPFC is one of the brain regions that directly related to abnormal behavior in the pathophysiology of OCD. The current meta-analysis indicates that cortices and sub-cortices contribute in different ways to the etiology of OCD.
Highlights
Frontal–subcortical circuits are effector mechanisms that allow an organism to act in its environment.[1]
The current meta-analysis revealed a significant NAA reduction in the frontal cortex in obsessive-compulsive disorder (OCD) patients, while no significant differences were present in the thalamus and basal ganglia
Sensitivity analysis in an anatomically specified subgroup consisting of datasets examining the medial prefrontal cortex (mPFC) demonstrated marginal significant reduction of NAA
Summary
Frontal–subcortical circuits are effector mechanisms that allow an organism to act in its environment.[1] Three cortico– striato–thalamo–cortical (CSTC) circuits originating from three prefrontal regions are important for the manifestation of neuropsychiatric behavior These circuits include the dorsolateral prefrontal cortex (DLPFC) circuit, which allows the organization of information to facilitate a response, the medial prefrontal cortex (mPFC) circuit, which is required for motivation-related behavior, and the orbitofrontal cortex (OFC) circuit, which allows the integration of limbic and emotional information into behavioral responses.[1]. Some studies reported altered activation in the frontal cortex including the OFC7–9 and mPFC,[7,8,10] others demonstrated abnormalities in the basal ganglia, including the striatum[10,11,12] and thalamus.[4]
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