Research report
Long-term follow-up of patients with obsessive–compulsive disorder treated by anterior capsulotomy: A neuropsychological study

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Abstract

Background

For treatment-refractory Obsessive–Compulsive-Disorder (OCD) patients, anterior capsulotomy is a potential therapy. We investigated what kinds of cognitive deficits treatment-refractory patients have and how anterior capsulotomy modifies their clinical and cognitive profiles.

Methods

Ten treatment-refractory OCD patients were examined in two groups (operated and non-operated) with 5 participants in each group, matched for symptom severity, gender, age and education. The operated group was treated with anterior capsulotomy; the non-operated group was treated only with pharmaco- and psychotherapy. The Yale–Brown Obsessive–Compulsive Rating Scale (Y-BOCS) was used to measure OCD symptoms, and ten neuropsychological tests were used to measure cognitive functioning.

Results

In the operated group, the score of Y-BOCS score significantly decreased during the two-year follow-up period. Additionally, we found a significant increase in neuropsychological test scores on the Wechsler Intelligence Test (MAWI), California Sorting Test Part A (CST-A), Stroop Test Interference Score (STR-I), Verbal Fluency Test and Iowa Gambling Test. As a negative result, we observed intrusion errors in the Category Fluency Test. In the non-operated group significant improvement was found in Y-BOCS scores. At follow-up, we found significant differences between the operated and non-operated groups on three neuropsychological tests: Trail Making Test Part B, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Index and RBANS Language Index, with better performance in the non-operated group.

Conclusions

Both treatment methods (i.e. anterior capsulotomy and pharmaco- and psychotherapy) seem effective in reducing OCD symptoms and cognitive deficits, but, importantly, to different degrees. The clinical and neuropsychological improvements were more impressive in the operated group.

Introduction

Over the last 30 years, remarkable developments have been made in the understanding of the underlying mechanism of obsessive–compulsive disorder (OCD). Despite the growing number of treatment options available, nearly 40% of OCD patients do not respond well to adequate therapeutic methods (Lopez et al., 2004). These patients are considered treatment-refractory patients. We define treatment-refractory OCD patients as those who undergo adequate trials of selective serotonin re-uptake inhibitors (SSRIs) (minimum 3 types of SSRI at maximum dosage for at least 12 weeks), standard augmentation strategies (two atypical antipsychotics) and behavior therapy (minimum 30 h) without satisfactory response (Husted and Shapira, 2004). Treatment-refractoriness might be considered one subtype of OCD. There is some evidence of treatment consequence resulting from the subtyping of OCD (Mataix-Cols et al., 1999) but relatively few studies have observed the features, cognitive profile and potential treatments of treatment-refractory OCD.

The appearance of neurosurgical methods was a breakthrough in managing treatment-refractory OCD patients (Jenike and Rauch, 1994). These neurosurgical methods cannot be understood without the most recent biological theories in OCD development, namely the loop theories. The loop theories (Modell et al., 1989, Baxter, 1999, Mashour et al., 2005, Cummings, 1993) describe the connections and interactions between neuro-anatomical structures involved in OCD and have been developed on the basis of neuro-imaging findings like structural (regional CT or MRI volume) (Szeszko et al., 1999, Kang et al., 2004) and functional (fMRI) (Whiteside et al., 2004) abnormalities in brain regions. These theories link the structural and functional results. In addition, an increasing amount of data is available on cognitive deficits in OCD patients from the late 1990s (Schmidtke et al., 1998, Miller & Cohen, 2001, Purcell et al., 1998, Cavallero et al., 2003). The most recent studies (Pujol et al., 1999, Kwon et al., 2003, Nakao et al., 2005, Rauch et al., 2007, Van der Wee et al., 2003) combine functional neuro-imaging techniques with neuropsychological tasks by imaging brain functions during cognitive testing in order to objectify the activity of given brain areas. In our opinion, alongside functional imaging and cognitive tests, neurosurgical methods can also provide insight into the function of loops.

Most neurosurgical techniques try to find a way to influence the connections between cortical areas (e.g., orbitofrontal cortex and cingulum), basal ganglia (mainly the caudate nucleus) and the medial dorsal thalamic nucleus.

Surgical interventions are used at certain locations of neuronal pathways, with a consequent effect on the whole network, thereby improving symptoms. Irreversible (e.g., cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior capsulotomy) and reversible (e.g., deep brain stimulation) surgical techniques can also be used for the treatment of patients with OCD. In the present study, we focus on anterior capsulotomy.

Studies using anterior capsulotomy can be divided into two groups: in the first, clinical condition is assessed prior to and after the surgical intervention, and changes in Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) scores serve as indicators of the effectiveness of the operation (Oliver et al., 2003, Christiensen et al., 2002, Mindus et al., 1994, Liu et al., 2008). Mindus et al. (1994) analyzed how the scores improved as a function of time elapsed after the surgery. They found that the biggest improvement occurred within the first two months after the operation and observed no significant change during later follow-up. That is, patients' symptoms did not improve after two months.

In the other group of studies, in addition to using the Y-BOCS severity scales, neuropsychological tests are also part of the pre- and post-operative examinations. This serves the measurement of cognitive functions of patients with OCD, not only as an indicator of the effectiveness of the operation. See details in Table 1.

Studies related to anterior capsulotomy and additional neuropsychological tasks are difficult to compare given the small number of patients involved and due to the diversity of used test batteries. Additionally, the results of such studies are inconsistent. The results of Fodstad et al.'s (1982) case study of two patients imply that the post-operative scores on intelligence and memory tests did not change significantly compared to pre-operative scores. In Nyman and Mindus's study (1995), the scores of neuropsychological tests fell into the normal range before capsulotomy and remained within the normal range after the operation. They found similar results for the same sample in 2001 (Nyman et al., 2001), when they compared the test results of patients who underwent operations with patients who did not: findings revealed no significant difference between the two groups.

In a review of two studies of capsulotomy and neuropsychology, Mindus and Meyerson (1995) concluded that intellectual functioning did not decrease after capsulotomy and that surgical intervention did not affect frontal lobe functions. Moreover, the authors state that certain cognitive functions even improved after the operation. These findings indicate possible significant improvement in the third and seventh post-operative years.

Rück et al. (2008) observed 25 OCD patients, who underwent anterior capsulotomy between 1988 and 2000 at the Karolinska Institut, Stockholm, Sweden. Although, the mean follow-up was ten years, only seven patients had pre- and post-operative neuropsychological test results. The investigators found that clinical and cognitive improvement stagnated after one post-operative year and concluded that there were no significant differences from the 1-year to the long-term follow-up ratings, implying that improvement was generally stable. Rück emphasized the importance of adverse effects in his follow-up. Rück et al. measured severe side effects (suicide, neurosurgical complications, weight gain, and executive dysfunctions) and concluded that capsulotomy is effective in treating OCD but carries a substantial risk of adverse effects.

To date, five anterior capsulotomies have been performed in Hungary. In our present study, we describe the pre-operative and post-operative follow-up conditions of five treatment-refractory OCD patients treated by anterior capsulotomy and combined pharmaco- and psychotherapy and five treatment-refractory OCD patients treated only with pharmaco- and psychotherapy. We also present detailed neuropsychological test results.

The aim of our study was two-fold. We wanted to characterize the underlying cognitive deficits in treatment-refractory patients. Second, we aimed to determine how the irreversible method of anterior capsulotomy modifies (by cutting through neural pathways and therefore influencing the function of loops) the cognitive profiles of patients during the course of the long-term follow-up, by comparing them to those of the non-operated matched clinical control group. In the present study, we did not use a healthy control group, as our aim was to determine the effect of surgery on cognitive profiles as a function of elapsed time since treatment.

Section snippets

Participants

In total, ten treatment-refractory OCD patients were included in the present study. Treatment-refractory status was defined by the following criteria: (i) a score of more than 32 on the Y-BOCS test, (ii) obsessive–compulsive symptoms did not respond to three different, adequately performed SSRI treatments; and (iii) psychotherapy (CBT) was ineffective (we used Husted and Shapira's guidelines, as mentioned above). Five patients were treated with anterior capsulotomy combined with pharmaco- and

Results for the operated group

Changes in the patients' clinical conditions were measured using three scales: the Y-BOCS, the HAM-A and the HAM-D during the course of the follow-up. Results are outlined in Table 3. Each of the patients who underwent surgery showed post-operative improvement. A significant decrease was found in Y-BOCS (χ2(4) = 12.93, p = < 0.01) and HAM-A (χ2(4) = 14.16, p < 0.01) scores, whereas there was a decrease in the scores of the HAM-D, but the overall result here showed only a tendency (χ2(4) = 7.46, ns).

Discussion

Few studies focus on treatment-refractory OCD patients, with most investigating potential treatments, i.e. psychosurgery (Rasmussen & Eisen, 1997, Jenike & Rauch, 1994, Liu et al., 2008). In the literature to date only one study has identified the possibility of the treatment-refractoriness as a subtype of OCD, and investigated its neuropsychological features (O'Connor, 2005). In the present study, we focused on treatment-refractory patients and their cognitive profiles. We observed ten

Role of funding source

We do not have any kind of financial support or funding for the present study.

Conflict of interest

The authors do not have an affiliation with, or financial interest in any organization that might pose a conflict of interest.

Acknowledgments

We would like to thank Dr László Döme for helpful comments on an earlier version of the manuscript.

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