Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder.

Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention significantly improves obsessive-compulsive disorder (OCD) symptoms in as little as 4 weeks. However, it has been thought that much longer treatment was needed to produce the changes in brain function seen in neuroimaging studies of OCD. We sought to elucidate the brain mediation of response to brief intensive CBT for OCD and determine whether this treatment could induce functional brain changes previously seen after longer trials of pharmacotherapy or standard CBT. [(18)F]-fluorodeoxyglucose positron emission tomography brain scans were obtained on 10 OCD patients before and after 4 weeks of intensive individual CBT. Twelve normal controls were scanned twice, several weeks apart, without treatment. Regional glucose metabolic changes were compared between groups. OCD symptoms, depression, anxiety and overall functioning improved robustly with treatment. Significant changes in normalized regional glucose metabolism were seen after brief intensive CBT (P=0.04). Compared to controls, OCD patients showed significant bilateral decreases in normalized thalamic metabolism with intensive CBT but had a significant increase in right dorsal anterior cingulate cortex activity that correlated strongly with the degree of improvement in OCD symptoms (P=0.02). The rapid response of OCD to intensive CBT is mediated by a distinct pattern of changes in regional brain function. Reduction of thalamic activity may be a final common pathway for improvement in OCD, but response to intensive CBT may require activation of dorsal anterior cingulate cortex, a region involved in reappraisal and suppression of negative emotions.

Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently.

BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.

BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).

A retrospective review of clinical characteristics and treatment response in body dysmorphic disorder versus obsessive-compulsive disorder.

BACKGROUND: Although body dysmorphic disorder (BDD) has many features in common with obsessive-compulsive disorder (OCD) and is frequently comorbid with OCD, few studies have directly compared the 2 disorders. Although BDD and OCD respond to similar medications and cognitive-behavioral therapy (CBT), their response to treatment has never been directly compared. METHOD: We studied 107 consecutive patients with DSM-III-R OCD (N = 96) or BDD (N = 11) treated openly for 6 weeks with intensive CBT, medication, and psychosocial rehabilitation, in a specialized partial hospitalization program for severely ill OCD patients. All patients were assessed, before and after treatment, with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Global Assessment Scale (GAS). Retrospectively, we compared the clinical characteristics, symptom severity, and response to treatment of BDD patients with those of OCD patients. RESULTS: BDD patients and OCD patients had similar sex ratio, age, treatment duration, prevalence of comorbid major depression, and pretreatment Y-BOCS and GAS scores. BDD patients had significantly higher pretreatment HAM-D and HAM-A scores. The proportions of patients treated with serotonin reuptake inhibitors and antipsychotics did not differ between groups. Both groups improved with treatment, with significant (p < .001) changes in Y-BOCS, HAM-D, HAM-A, and GAS scores. Change in Y-BOCS did not differ between groups, but changes in HAM-D and HAM-A were significantly greater in BDD patients than in OCD patients. CONCLUSION: While BDD may be associated with greater severity of depressive and anxiety symptoms than OCD, this study suggests that BDD may respond to intensive, multimodal treatment.

Personality changes in adult subjects with major depressive disorder or obsessive-compulsive disorder treated with paroxetine.

BACKGROUND: Human and animal studies point to 3 dimensions of personality that change during pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI). Specifically, harm avoidance has been found to decrease, social dominance has been found to increase, and hostility in social situations has been found to decrease with SSRI treatment. We sought to determine personality changes in subjects with either major depressive disorder (MDD) or obsessive-compulsive disorder (OCD) treated with paroxetine. We also sought to determine whether or not these personality changes were associated with disease state (MDD vs. OCD) or treatment response (responders vs. nonresponders). METHOD: Thirty-seven subjects diagnosed with either MDD or OCD (according to DSM-IV criteria) completed the Cattell 16 Personality Factor Inventory (16-PF) before and after treatment with paroxetine. Treatment response was defined as a Clinical Global Impressions-Improvement rating of "much" or "very much" improved and a drop in Hamilton Rating Scale for Depression score of at least 50% for MDD or Yale-Brown Obsessive Compulsive Scale score of at least 30% for OCD. RESULTS: No significant differences were found between subjects with MDD and OCD in personality change with treatment. In the whole group, treatment responders had a greater decrease than nonresponders in 16-PF factors relating to harm avoidance. An increase in social dominance factors and a decrease in factors relating to hostility in social situations were found, but these changes were not significantly different between responders and nonresponders. CONCLUSION: These findings indicate that certain personality dimensions change with SSRI treatment and that some of these changes are independent of clinical treatment response.

Quality-of-life changes among patients with obsessive-compulsive disorder in a partial hospitalization program.

Thirty treatment-resistant patients with a primary DSA-IV diagnosis of obsessive-compulsive disorder were assessed at admission to and discharge from a partial hospitalization program to determine whether improvement in symptoms of the disorder was associated with improvements in patients' quality of life. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (YBOCS). Quality of life was measured using Lehman's Quality of Life (QOL) scale, which includes several objective and subjective indexes. YBOCS scores significantly improved with treatment, as did scores on the majority of the QOL subjective indexes and on the objective social, health, and activity indexes. No significant association between changes in YBOCS scores and QOL scores was found.

Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.

Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.

Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.

FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder.

In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.