Objective: Neuroimaging studies have suggested that the dysfunction of the cortico-striatal-thalamo-cortical circuit was a key pathophysiological feature of Obsessive compulsive disorder (OCD). Several studies have investigated abnormalities in the neural metabolite concentrations and metabolic changes after OCD treatments, using proton magnetic resonance spectroscopy (1H-MRS) among OCD patients. The aim of this study was to investigate the metabolic integrity of the anterior cingulate, caudate and putamen and the effects of the selective serotonin reuptake inhibitor (SSRI) treatment on neurochemical levels in OCD patients.
Methods: In the present study, 32 unmedicated OCD patients were compared with 32 healthy controls to assess metabolite levels in the anterior cingulate, caudate and putamen by using 1H-MRS. 19 of the patients underwent a sertraline treatment for 12 weeks. Baseline metabolite levels in the three brain regions of 19 patients with OCD were compared with the levels measured after 12 weeks of sertraline treatment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D) were administered to the patients at baseline and after 12 weeks of sertraline treatment. In OCD patients, at baseline and after pharmacotherapy, and in all control subjects, conventional cranial MR imaging and 1H-MRS examinations were performed on a 1.5T superconducting whole-body MR imaging scanner and spectroscopic system. Levels of N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) were measured in terms of their ratios with creatine (Cr). Student’s t test was used for continuous demographic variables for comparisons between the OCD and healthy control groups. Paired t tests were employed to compare the metabolite ratios and the scores on the scales before and after 12 weeks of sertraline treatment. Pearson’s correlation coefficients were computed between the clinical variables and levels of metabolites.
Results: The ratio of NAA/Cr was significantly lower in OCD patients than in healthy controls in the anterior cingulate (t=-3.17, p=0.002). There was a tendency for levels of NAA/Cr to be lower in the caudate in OCD patients compared with healthy controls (t=-1.98, p=0.05). NAA/Cr ratios were negatively correlated with the Y-BOCS-total scores in the anterior cingulate in OCD patients (r=-0.57, p=0.001). There were significant improvements in the Y-BOCS-total score after 12 weeks of sertraline treatment, compared with baseline assessments (t=8.44, p<0.001). There was a mean reduction of 41.6% on the Y-BOCS-total score after the treatment. NAA/Cr levels were significantly higher in OCD patients after 12 weeks of sertraline treatment compared to those at baseline in the anterior cingulate (t=-2.41, p=0.027) and in the caudate (t=-2.23, p=0.039).
Conclusion: Neuroimaging studies of OCD have suggested abnormalities in the orbitofrontal cortex, anterior cingulate, and caudate nucleus. It has been also proposed that OCD treatment with the aim of reducing symptoms may have a neuromodulatory effect leading to metabolic changes in the direction of normalization in these regions. Our results suggest that reductions in NAA in the anterior cingulate and caudate could be reversed with SSRI treatment, which may indicate an improvement in neuronal integrity in OCD patients.