Eriko Nakatani

Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: A functional magnetic resonance imaging study

BACKGROUND Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder (OCD); however, relationships between abnormal brain activity, clinical improvement, and neuropsychological function have not been clarified in OCD. To clarify the pathophysiology of this disorder, regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment. METHODS Ten outpatients with OCD participated in the study. Functional magnetic resonance imaging (fMRI) was performed before and after treatment. Stroop and symptom provocation tasks were administered during fMRI. Each patient was randomly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day (n = 4) or behavior therapy (n = 6) for 12 weeks. RESULTS After 12-week treatment, mean (+/- SD) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 +/- 3.59 to 14.60 +/- 9.22, representing symptomatic improvement from moderate to mild. After symptom improvement, symptom provocation-related activation in the orbitofrontal, dorsolateral-prefrontal, and anterior cingulate cortices decreased. Conversely, Stroop task-related activation in the parietal cortex and cerebellum increased. CONCLUSIONS After improvement of OCD with either fluvoxamine or behavioral therapy, hyperactivation of the frontal lobe related to a symptom-provocative state decreases, and posterior brain activity related to action-monitoring function increases.

Structure of obsessive-compulsive symptoms in pediatric OCD.

OBJECTIVE It is unclear whether the structure of obsessive-compulsive disorder (OCD) symptoms seen in adults is preserved in pediatric samples. METHOD A total of 238 children and adolescents referred to a specialty pediatric OCD clinic were administered the Childrens Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 major symptom categories were subjected to exploratory principal components analysis. The resulting factors were correlated with relevant clinical variables. RESULTS Principal components analysis identified four symptom dimensions explaining 55% of the total variance and broadly corresponding to those seen in adult samples. Boys were more likely to have sexual obsessions (34% vs. 18%, p = .01), whereas girls were more likely to endorse hoarding compulsions (53% vs. 36%, p=.009). High scores on the hoarding dimension were associated with increased levels of pervasive slowness, responsibility, indecisiveness, pathological doubt, depression and a variety of emotional difficulties, both self-rated and parent-rated. CONCLUSIONS The structure of OCD symptoms is similar across the lifespan. Hoarding symptoms are prevalent in pediatric OCD, especially among girls, and are associated with greater levels of disability.

Effects of behavior therapy on regional cerebral blood flow in obsessive–compulsive disorder

Very few functional neuroimaging studies have been performed on patients with obsessive-compulsive disorder (OCD) undergoing behavior therapy, even though it is recognized to be an effective treatment for this disorder. We measured the regional cerebral blood flow (rCBF) using the Xenon inhalation method in 31 treatment-refractory patients with OCD and the same number of age-matched normal controls. We also studied changes in rCBF in 22 OCD patients who had demonstrated a significant improvement after the behavior therapy. The OCD patients showed a significant bilateral elevation in the rCBF in the basal ganglia compared with the normal controls. After successful treatment, a significant decrease was found in the rCBF in the right head of the caudate nucleus that tended to correlate with clinical improvement.

Long-term outcomes of obsessive–compulsive disorder: follow-up of 142 children and adolescents

BACKGROUND Obsessive-compulsive disorder (OCD) often starts in childhood and adolescence and can be a chronic disorder with high persistence rates. There are few prospective long-term follow-up studies. AIMS To follow up young people with OCD to clarify persistence rates and relevant predictors, presence of other psychiatric disorders, functional impairment, service utilisation and perceived treatment needs. METHOD All young people with OCD assessed over 9 years at the National and Specialist Paediatric OCD clinic, Maudsley Hospital, London, were included. Sixty-one per cent (142 of 222) of all contactable young people and parents completed computerised diagnostic interviews and questionnaires. RESULTS We found a persistence rate of OCD of 41%; 40% of participants had a psychiatric diagnosis other than OCD at follow-up. The main predictor for persistent OCD was duration of illness at assessment. High levels of baseline psychopathology predicted other psychiatric disorders at follow-up. Functional impairment and quality of life were mildly to moderately affected. Approximately 50% of participants were still receiving treatment and about 50% felt a need for further treatment. CONCLUSIONS This study confirms that paediatric OCD can be a chronic condition that persists into adulthood. Early recognition and treatment might prevent chronicity. Important challenges for services are ensuring adequate treatment and a smooth transition from child to adult services.

Functional MRI study of brain activation alterations in patients with obsessive–compulsive disorder after symptom improvement

Dysfunction of the frontal-subcortical circuits has been the most common finding in the pathophysiology of obsessive-compulsive disorder (OCD), and recent neuropsychological studies have shown cognitive impairments in OCD. To clarify the pathophysiology of OCD without the confounding effects of medication, we investigated the alterations of brain function in OCD patients and changes after clinical improvement due solely to behavior therapy. The participants were 11 outpatients with OCD and 19 normal controls. The patients received 12 weeks of behavior therapy. We investigated the differences in the behavioral performance and functional magnetic resonance imaging results during the Stroop test in the patients and normal controls, and their changes after treatment in the patients. The patients showed less activation in the anterior cingulate gyrus and cerebellum than control subjects. Following significant improvement in OC symptoms, the cerebellum and parietal lobe showed increased activation, and the orbitofrontal cortex, middle frontal gyrus, and temporal regions showed decreased activation during the Stroop task, and performance of the task itself improved. Our findings suggest that dysfunction of the posterior brain regions, especially the cerebellum, is involved in the pathogenesis of OCD, and that normalization in function can occur with improvement of OC symptoms.

Working memory dysfunction in obsessive–compulsive disorder: A neuropsychological and functional MRI study

Previous neuropsychological studies indicate that OCD subtypes such as checking rituals might be associated with a working memory deficit. On the other hand, functional neuroimaging studies found functional abnormalities of the frontal cortex and subcortical structures in OCD. Combined with functional imaging method, we applied neuropsychological batteries to demonstrate a working memory deficit in OCD by comparison with normal controls. In addition, working memory and brain activation were further examined with symptom-based analysis. Forty patients with OCD and 25 normal controls were examined using neuropsychological tests including the WAIS-R, WCST, WMS-R, and R-OCFT and functional MRI (fMRI) during the N-back task including 0- and 2-back task. On fMRI, the brain regions activated during the performance and the differences in the activation between patients and controls were identified. Additional analyses of severity and subtypes were conducted by using Y-BOCS severity score, symptom-checklist and Leckmans four-factor model, respectively. On the neuropsychological tests, the OCD patients had significantly lower scores on the delayed recall section of the WMS-R and the immediate recall section of the R-OCFT compared to the controls. On fMRI, the patients showed greater activation in the right dorsolateral prefrontal cortex (DLPFC), left superior temporal gyrus (STG), left insula, and cuneus during two-back task compared to the controls. Right orbitofrontal cortex activity showed a significant positive correlation with Y-BOCS scores in OCD. Furthermore, patients with obsessions/checking rituals (n=10) showed severer memory deficits and decreased activity in the postcentral gyrus than patients with cleanliness/washing rituals (n=14). In conclusion, we found neuropsychological dysfunction and brain abnormalities in OCD. Furthermore, our results suggested that symptom severity and symptom subtype such as obsessions/checking might affect neuropsychological dysfunction and related brain activities.

A functional MRI comparison of patients with obsessive–compulsive disorder and normal controls during a Chinese character Stroop task

Recent functional neuroimaging and neuropsychological studies have suggested that abnormal activity in the anterior cingulate cortex (ACC) might cause an action-monitoring dysfunction in obsessive-compulsive disorder (OCD). To identify the relationship between brain dysfunction and cognitive dysfunction, we examined regional brain changes in OCD with functional magnetic resonance imaging (fMRI) during the performance of a cognitive task. Participants comprised 24 patients with OCD and 14 normal controls. First, we compared the cognitive function in the two groups as assessed by several neuropsychological tests. Then we used fMRI to explore brain correlates of their performance during the Chinese character version of the Stroop test, a task that is strongly related to action-monitoring function. The two groups did not differ on the neuropsychological tests. Both groups also showed similar activation pattern on fMRI. The patients, however, showed weaker activation than the normal controls in the ACC and the right caudate nucleus.

A Randomized Controlled Trial of Japanese Patients with Obsessive-Compulsive Disorder – Effectiveness of Behavior Therapy and Fluvoxamine

Background: The aim of this study was to confirm and compare the efficacy of fluvoxamine (the only licensed SSRI for treatment for OCD in Japan) and behavior therapy in treating Japanese patients with OCD. In addition, we investigated predictors of these treatments. Methods: Thirty-one outpatients meeting the DSM-III-R criteria for OCD without any axis I disorder were randomly assigned to one of three treatment conditions: BT (behavior therapy ± pill placebo), FLV [autogenic training (a psychological placebo for OCD) ± fluvoxamine] and control group [autogenic training (psychological placebo) ± pill placebo] for 12 weeks of treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement Scale (CGI-I) were administered blindly at baseline and week 4, 8 and 12. Results: Twenty-eight patients completed this study. Patients in the BT and FLV groups showed significantly more improvement than those in the control group in the mean score of total Y-BOCS; moreover, the BT group showed significantly more reduction in total Y-BOCS score at the end of treatment than the FLV group (BT > FLV, p < 0.01). Patients with lower baseline total Y-BOCS, past history of a major depressive episode and absence of cleaning compulsion improved more with fluvoxamine. Conclusions: We confirmed the effectiveness of behavior therapy and fluvoxamine for Japanese patients with OCD. Behavior therapy improved the condition of OCD patients more than fluvoxamine.

Children with very early onset obsessive-compulsive disorder: clinical features and treatment outcome

BACKGROUND There is emerging evidence that early onset obsessive-compulsive disorder (OCD) may be a phenomenologically distinct subtype of the disorder. Previous research has shown that individuals who report an early onset display greater severity and persistence of symptoms, and they may be less responsive to treatment. To date, this question has been investigated solely in adult samples. The present study represents the first investigation into the effect of age at onset of OCD on clinical characteristics and response to treatment in a paediatric sample. METHOD A total of 365 young people referred to a specialist OCD clinic were included in the study. Clinical records were used to examine potential differences in key clinical characteristics between those who had a very early onset of the disorder (before 10 years) and those who had a late onset (10 years or later). Group differences in treatment responsiveness were also examined within a subgroup that received cognitive behaviour therapy (CBT) alone or CBT plus medication (n = 109). RESULTS The very early onset group were characterised by a longer duration of illness, higher rates of comorbid tics, more frequent ordering and repeating compulsions and greater parent-reported psychosocial difficulties. There were no differences in treatment response between the groups, and when age at onset was examined as a continuous variable, it did not correlate with treatment response. CONCLUSIONS Very early onset OCD may be associated with different symptoms and comorbidities compared with late onset OCD. However, these differences do not appear to impact on responsiveness to developmentally tailored CBT alone or in combination with medication. These findings further indicate the value in early detection and treatment of OCD in childhood.

Predictors of treatment response to fluvoxamine in obsessive–compulsive disorder: An fMRI study

Recent neuroimaging studies suggest that the pathophysiology of obsessive-compulsive disorder (OCD) may involve more widely distributed large-scale brain systems, including the parietal, occipital, and cerebellar areas, rather than the conventional orbitofronto-striatal model. We hypothesized that not only orbitofrontal cortex and caudate nucleus activities but also posterior brain regions might be associated with subsequent treatment response to serotonin reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before treatment, fMRI images of the subjects were obtained in the context of a symptom-provocation paradigm. The percentage changes in total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the index of treatment response. Statistical Parametric Mapping was used to identify brain loci where pre-treatment brain activation significantly correlated with the subsequent treatment response. Fifteen of 17 patients completed the 12-week treatment. During the symptom provocation task, patients showed brain activation in the left superior temporal gyrus (STG), left precuneus, left frontal cortices, right cerebellum, and right frontal cortices. We found that pre-treatment activation in the right cerebellum (Z-score=5.10, x,y,z=22,-84,-18) and the left STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score. Our results suggest that pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity. There is every possibility that fMRI can be used as a tool to predict treatment response.