Volumetric MRI assessment of brain regions in patients with refractory obsessive–compulsive disorder

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Abstract

No prior study to date has examined the comparisons of the structures that have been implicated in obsessive–compulsive disorder (OCD) in patients with refractory OCD, those who are treatment-responded and healthy controls concurrently. Therefore, we performed a volumetric MRI study in patients with refractory OCD, those with treatment responding OCD and healthy controls. Morphometric MRI was used to compare in thirty patients with OCD and ten healthy controls. Of the patient group, ten were first applying patients, ten were treatment-responded and the rest were refractory OCD patients. As a whole group, OCD patients had increased white matter volume than healthy controls. First applying patients had significantly smaller left and right orbito-frontal cortex (OFC) volumes compared with treatment-responded patients and healthy controls, with a significant difference between refractory patients and treatment-responded patients and with no significant difference was found between the volume of first applying patients compared to that of refractory patients. Anterior cingulate exhibited a near-significant difference only between first applying patients and healthy controls on left side. First applying patients had significantly greater left and right thalamus volumes compared with treatment-responded patients and healthy controls and there was a considerable difference in regard to thalamic volumes between refractory patients and treatment-responded patients. Taken together, our findings suggest that reductions in OFC and increase in thalamic volumes may be associated with refractoriness of OCD and may not be due to changes in cingulate and caudate regions.

Introduction

Obsessive–compulsive disorder (OCD) is characterized by intrusive unwanted thoughts, ideas, or images that are distressing (obsessions) and urges to perform ritualistic behaviors or mental acts (compulsions) to reduce this distress. The lifetime prevalence is estimated to be 2–3% around the world (Weissman et al., 1994). OCD is associated with impairment in occupational, academic, and social functioning (Koran et al., 1996), and can sometimes involve self-injury, such as skin damage from excessive hand washing. Although symptoms tend to wax and wane through the course of the disorder, OCD symptoms rarely remit spontaneously. Given the prevalence, course, and functional interference associated with OCD, it is important to elucidate variables underlying this disorder.

Recent neurobiological models have postulated that abnormalities in brain activity underlie the etiology of OCD. Specifically, experts implicate dysfunction in the orbito-frontal–subcortical circuits. These circuits are thought to connect regions of the brain that process information involved in the initiation of behavioral responses that are implemented with little conscious awareness (Saxena et al., 2001). Neurobiological theories of OCD are largely derived from results of functional neuroimaging studies. Functional imaging techniques indirectly measure activity levels in specific brain areas and therefore are used to determine whether the structures thought to be involved in OCD are abnormally active in patients with this disorder. Despite abnormalities reported in neuropsychological and functional imaging literature, the findings from structural imaging studies have been inconsistent, with reports of increases (Scarone et al., 1992), decreases (Robinson et al., 1995, Szeszko et al., 1999) or no differences (Jenike et al., 1997, O'Sullivan et al., 1997, Bartha et al., 1998) in the volumes of these key brain regions.

In summary, the studies examining the structures that have been implicated in OCD mostly had naturalistic design, and no OCD study to date has examined the comparisons of these regions in patients with refractory OCD, those with treatment responding and healthy controls. Therefore, we performed a volumetric MRI study in patients with refractory OCD, those with treatment responding and healthy controls patients focusing on the in vivo neuroanatomy of the whole brain, total gray and white matter volume, thalamus, caudate nucleus, anterior cingulate cortex, and orbito-frontal cortex (OFC) concurrently.

Section snippets

Subjects and clinical evaluations

Thirty patients with OCD were recruited from Firat University School of Medicine Department of Psychiatry. Of them, ten were first applying patients who never had taken any drug for this condition, ten were treatment-responded and the rest were refractory patients. Treatment responding patients were selected among first applying OCD patients who were treated for an a selectie serotonin reuptake inhibitors (SSRI) for eight weeks and demonstrated 50% or more reduction on the Yale–Brown

Results

There were no significant differences in demographic variables of age, gender composition, educational level, and intracranial volume (ICV) among drug-free patients, those with well-responding OCD, refractory OCD patients and healthy controls (p > 0.05).

ICV (1438.4 ± 140.5 mm3 for drug-free patients, 1440.8 ± 151.2 mm3 for well-responding patients, 1451.0 ± 142.9 mm3 for refractory patients and 1448.5 ± 145.2 mm3 for controls), whole brain volume (1149.1 ± 120.6 mm3 for drug-free patients, 1158.8 ± 149.3 mm3

Discussion

This is the first study regarding structural investigation of brain regions in refractory OCD patients. Thus, we would like to emphasize the main findings found in the present study: (i) As a whole group, OCD patients had increased white matter volume than healthy controls, (ii) first applying patients had significantly smaller left and right OFC volumes compared with treatment-responded patients and healthy controls. In addition, there was a significant difference between refractory patients

Conclusion

This initial morphometric MRI study of refractory OCD patients shows that first applying OCD patients had significantly smaller left and right OFC volumes compared with treatment-responded patients and healthy controls but similar with refractory patients as well as considerable greater left and right thalamus volumes in first applying patients compared with treatment-responded patients and healthy controls with no difference between refractory patients and first applying patients. Taken

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