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.

Executive dysfunction predicts nonresponse to fluoxetine in major depression.

BACKGROUND: Functional brain imaging studies of major depression have consistently revealed hypometabolism or hypoperfusion in specific regions of the prefrontal cortex and basal ganglia. Studies of cognitive functioning in major depression have suggested that some but not all subjects exhibit cognitive deficits that are consistent with frontal-subcortical dysfunction, although the reasons for this heterogeneity are unclear. In this study, we explored this heterogeneity among depressed subjects by examining the relationship between cognitive functioning and treatment outcome. METHOD: Subjects with major depression were administered a complete neuropsychological test battery prior to treatment with fluoxetine. RESULTS: There were no significant differences between responders and nonresponders to fluoxetine in terms of age, educational achievement, number of past episodes of depression, and estimated premorbid IQ. However, nonresponders performed significantly worse than responders on several pretreatment measures of executive functioning, after controlling for baseline group differences in depression severity. LIMITATIONS: The results are based on a small sample of primarily female subjects, resulting in low statistical power and less generalizability to samples of male subjects with depression. CONCLUSIONS: The findings suggest that subtle prefrontal dysfunction in subjects with major depression may be predictive of poor response with particular medications. Assessment of the executive functions may play a particular role in pretreatment identification of subjects likely to respond to specific medications.

Neurophysiologic predictors of treatment response to fluoxetine in major depression.

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.

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.

Dementia caregiver burden: a review of the literature and guidelines for assessment and intervention.

Alzheimer's disease (AD) and other dementias are common degenerative disorders in the elderly. Most AD patients are cared for at home by family members, usually elderly spouses. Although caregiving is associated with significant psychological and physical morbidity, there are wide individual differences among caregivers in how well they adapt to caregiving demands. In addition, recent data suggest that caregiver variables can be important determinants of AD patient institutionalization and that AD patients living with highly distressed caregivers may exhibit higher frequencies of behavioral problems and agitation than those living with less distressed caregivers. Predictors of caregiver outcome, predictors of institutionalization, and the effect of the caregiver on the course and symptomatology of dementia are described. A model of assessment and intervention for the physician, referral processes, and resources for the caregiver are presented.

Relationships between EEG coherence and neuropsychological tests in dementia.

Previous research has demonstrated differences in resting state EEG coherence among groups of subjects with dementia of the Alzheimer type (DAT), multi-infarct dementia (MID), and normal elderly controls. Since reduced coherence between brain sites has been thought to reflect functional disconnection between brain areas, we hypothesized that decreased coherence would be associated with cognitive dysfunction as assessed by neuropsychological tests. We correlated several neuropsychological tests with four coherence variables and found that reduced coherence was associated with impairment on specific neuropsychological tests in ways that conform to and supplement current knowledge about the localization of brain functions. The results are consistent with the hypothesis that coherence reflects a functional breakdown in communication between brain areas, and that coherence may be a more precise way to localize brain function than other EEG variables.

Effect of white matter disease on functional connections in the aging brain.

Periventricular white matter hyperintensities (PVHs) seen on T2 weighted MRI studies are common in elderly people and often represent demyelination of fibres. Damage to these fibres could lead to functional disconnection between brain regions. Electroencephalographic coherence, a measure of shared electrical activity between regions, was examined to determine if there was evidence for such disconnection. Twenty two subjects with clinically diagnosed dementia of the Alzheimer's type, 16 with multi-infarct dementia, and 18 normal controls were studied. It was hypothesised that coherence between areas presumably linked by fibres that traverse the periventricular region would be decreased in subjects with PVHs, and that PVHs would have a stronger association with decreased coherence than clinical diagnosis. It was also hypothesised that coherence between areas presumably connected by long corticocortical tracts that are neuroanatomically separated from the ventricles would be low in patients with Alzheimer's disease because of pyramidal cell death in this group, but would not be affected by the presence of PVHs. Patients with PVHs in fact had lower coherence than those without PVHs in the pre-Rolandic and post-Rolandic areas, where connecting fibres traverse the periventricular region. There was no effect of PVHs, however, on coherence between areas separated by the Rolandic fissure that were connected by long corticocortical tracts; this coherence was lowest among the patients with Alzheimer's disease. These patterns of association suggest that coherence may detect different types of neurophysiological "disconnection," and may be sensitive to selective damage to different fibre pathways.

Assessment of cerebral perfusion using quantitative EEG cordance.

Brain electrical activity is related to cerebral perfusion. The nature of this relationship is unclear, however, and surface-recorded activity has not been a reliable indicator of brain perfusion. We studied 27 subjects, all of whom were examined with single photon emission tomography (SPECT) and quantitative electroencephalography (QEEG), to assess associations between QEEG cordance and relative brain perfusion. Cordance has two indicator states: concordance, which may indicate high perfusion; and discordance, which may indicate low perfusion. We used multiple linear regression to assess the association between cordance and SPECT values, and found that cordance values were strongly associated with tissue perfusion. Concordance in the alpha band was associated both with mean tissue perfusion and the volume of normally perfused tissue, and it had a stronger association with perfusion than any other QEEG variable. Discordance in the beta 1 band was associated with mean perfusion, and it had a stronger association than did relative but not absolute power. These data suggest that cordance may be useful for the noninvasive assessment of brain perfusion.

Reduced EEG coherence in dementia: state or trait marker?

Recent work from our laboratory demonstrated that quantitative electroencephalographic (EEG) coherence between brain areas linked by long cortico-cortical fibers (termed "fascicle" coherence) was differentially reduced in subjects with Alzheimer's disease, whereas coherence between brain areas linked by short cortico-cortical and cortico-subcortical fibers in postcentral areas (termed "visual" coherence) was differentially reduced in subjects with multi-infarct dementia. In this study, we investigated whether these differences in coherence represent "trait" or "state" markers for dementia. Visual coherence demonstrated high stability in both demented groups as assessed by both one-year test-retest reliabilities and analysis of group mean change. Fascicle coherence demonstrated good stability in multi-infarct dementia and control subjects, but some variability was observed in Alzheimer's subjects, suggesting both state and trait factors may be involved. These findings complement neuropathologic studies, and suggest that decreases in coherence may serve as a diagnostic trait markers for these two types of dementia. The role of state factors in Alzheimer's disease requires further investigation.