Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive–compulsive disorder: A diffusion tensor imaging study

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Abstract

Background

Abnormalities of fractional anisotropy (FA) have been reported in previous diffusion tensor imaging (DTI) studies in patients with obsessive–compulsive disorder (OCD). However, there are some inconsistencies in the results and the apparent diffusion coefficient (ADC) has not been investigated. The goal of this study was to investigate white matter abnormalities and water diffusivity, as reflected by FA and ADC, using DTI in patients with OCD.

Methods

Fifteen patients with OCD and 15 healthy volunteers underwent DTI. Voxelwise analysis was used to compare FA in white matter and ADC in gray matter/white matter of the two groups.

Results

Compared with healthy volunteers, the patients had higher FA in the bilateral semioval center extending to the subinsular white matter; and a higher ADC in the left medial frontal cortex. There were no areas with a significantly lower FA or ADC in patients compared with healthy volunteers.

Conclusions

A significantly higher FA was found in regions associated with the emotion of disgust and a trend for a higher ADC was found in a region associated with the regulation of emotions. These findings suggest that neurocircuits involved in disgust processing may play an important role in the pathophysiology of OCD.

Introduction

Obsessive–compulsive disorder (OCD) is a common psychiatric disorder characterized by the presence of obsessions, compulsions or both. OCD has a lifetime prevalence rate of 2% to 3% in the general population and is marked by significant and often chronically disabling functional impairment. OCD is considered to be among the twenty leading causes of disability in the United States and other countries (Michaud et al., 2006). Abnormal feedback loops within cortical–striatal–thalamic–cortical circuits have been hypothesized to play a key role in the pathophysiology of OCD (Rapoport and Wise, 1988, Baxter et al., 1992). Moreover, a recent genetic family-based association study showed that oligodendrocyte lineage transcription factor 2 (OLIG2), which is an essential regulator in the development of cells that produce white matter (myelin), is associated with OCD (Stewart et al., 2007). However, little attention has been paid to the functional white matter network in patients with OCD.

The diffusion tensor imaging (DTI) technique has made it possible to examine white matter microstructure in humans. DTI detects self-diffusion of a water molecule. Water molecules can diffuse freely in solution without obstacles, but in human tissue (and especially in white matter) water molecules diffuse anisotropically along neural fibers. Indices used to interpret DTI data include fractional anisotropy (FA) and the apparent diffusion coefficient (ADC). FA reflects directionality and coherence of water self-diffusion: tissues with highly regular fibers have high anisotropy, whereas those with less regular fibers, such as gray matter, have low anisotropy. Therefore, FA abnormalities in white matter may reflect abnormalities in the myelin sheath and/or directional coherence of fiber tracts. The ADC reflects the degree of apparent water diffusivity: tissues without obstacles, such as cerebrospinal fluid (CSF), have high water diffusivity, whereas those with obstacles, such as white matter, have low diffusivity.

Szeszko et al. (2005) found white matter abnormalities characterized by lower FA in the bilateral anterior cingulate gyrus region, bilateral parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). Cannistraro et al. (2007) also reported lower FA in the right cingulum bundle, and higher FA in the left cingulum bundle and the left anterior limb of the internal capsule in patients compared with healthy volunteers. Both studies reported FA abnormalities in the anterior cingulate region. Evidence from structural MR (Valente et al., 2005) and functional neuroimaging (Rauch et al., 1994) has also implicated anterior cingulate abnormalities in the pathogenesis of OCD. However, a recent DTI study in drug-naïve OCD patients showed no FA abnormalities in the anterior cingulum (Yoo et al., 2007). Thus, the results of previous studies are inconsistent. Given this background, we performed DTI to investigate FA abnormalities in the whole brain, with particular attention to the anterior cingulum.

We also examined the ADC, which has not been investigated previously in patients with OCD. ADC abnormalities were originally reported in neurological diseases such as multiple sclerosis and temporal lobe seizures (Maldjian and Grossman, 2001, Londono et al., 2003). However, ADC has recently been investigated in psychiatric disorders such as schizophrenia and mood disorder (DeLisi et al., 2006, Regenold et al., 2006, Shin et al., 2006), and DeLisi et al. have suggested that ADC may be more sensitive to brain abnormalities compared to volume assessments. Therefore, the ADC may be of value in understanding the mechanism of OCD.

Section snippets

Participants

The subjects were 15 adult patients diagnosed with OCD according to DSM-IV criteria and 15 healthy volunteers matched for age, sex, handedness, and education (Table 1). We defined duration of illness as the time from the beginning of the present episode to the time of MRI acquisition. All except one of the patients had a single episode; one patient had two episodes with a long inter-episode period of full recovery in his clinical history. Patients were recruited at the Kyoto Prefectural

Results

Age, sex, handedness, and education did not differ significantly between patients with OCD and healthy volunteers (Table 1). Compared with the healthy volunteers, the patients did not show FA abnormalities in the anterior cingulum, even with a liberal threshold (p < 0.05, uncorrected, 2-tailed), and no other areas had regions of significantly lower FA using an adequate threshold (p < 0.001, uncorrected; 2-tailed). The patients had higher FA in the bilateral semioval center extending to the

Discussion

Compared with healthy volunteers, our results indicate that patients with OCD had higher FA in the bilateral semioval center extending to the subinsular white matter and a higher ADC in the left medial frontal gyrus. On the other hand, FA abnormality in the anterior cingulum was not detected. To our knowledge, this is the first study of the ADC in OCD patients.

Our patients demonstrated higher FA in the bilateral semioval center extending to the subinsular white matter, compared with healthy

Conclusion

A significantly higher FA was found in regions associated with the emotion of disgust and a trend for a higher ADC was found in a region associated with the regulation of emotions. These findings suggest that neurocircuits involved in disgust processing may play an important role in the pathophysiology of OCD.

Acknowledgement

This study was supported by a Grant-in-Aid for Young Scientists (B) (16790699) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Dr. Yoshida).

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