Jennifer L. Greenberg

Deficits in Conditioned Fear Extinction in Obsessive-Compulsive Disorder and Neurobiological Changes in the Fear Circuit

IMPORTANCE Obsessive-compulsive disorder (OCD) may be characterized by impaired self-regulation and behavioral inhibition. Elevated fear and anxiety are common characteristics of this disorder. The neurobiology of fear regulation and consolidation of safety memories have not been examined in this patient population. OBJECTIVE To examine the psychophysiological and neurobiological correlates of conditioned fear extinction in patients with OCD. DESIGN Cross-sectional, case-control, functional magnetic resonance imaging study. SETTING Academic medical center. PARTICIPANTS Twenty-one patients with OCD and 21 healthy participants. MAIN OUTCOMES AND MEASURES Skin conductance responses and blood oxygenation level-dependent responses. RESULTS The between-group difference noted in our psychophysiological measure (skin conductance responses) was during extinction recall: patients with OCD showed impaired extinction recall relative to control subjects. Regarding the functional magnetic resonance imaging data, patients with OCD showed significantly reduced activation in the ventromedial prefrontal cortex across training phases. Moreover, reduced activation in the patients with OCD was noted in the caudate and hippocampus during fear conditioning, as well as in the cerebellum, posterior cingulate cortex, and putamen during extinction recall. Contrary to our prediction, OCD symptom severity was positively correlated with the magnitude of extinction memory recall. Also contrary to our prediction, functional responses of the ventromedial prefrontal cortex were positively correlated with symptom severity, and functional responses of the dorsal anterior cingulate cortex were inversely correlated with symptom severity. CONCLUSIONS AND RELEVANCE As expected, our study showed that fear extinction and its neural substrates are impaired in patients with OCD. However, this study also yielded some surprising and unexpected results regarding the correlates between extinction capacity and its neural substrates and the severity of symptoms expressed in this disorder. Thus, our data report neural correlates of deficient fear extinction in patients with OCD. The negative correlations between fear extinction deficits and Yale-Brown Obsessive-Compulsive Scale symptoms in OCD suggest that there may be other factors, in addition to fear extinction deficiency, that contribute to the psychopathology of OCD.

Modular Cognitive-Behavioral Therapy for Body Dysmorphic Disorder: A Randomized Controlled Trial

There are few effective treatments for body dysmorphic disorder (BDD) and a pressing need to develop such treatments. We examined the feasibility, acceptability, and efficacy of a manualized modular cognitive-behavioral therapy for BDD (CBT-BDD). CBT-BDD utilizes core elements relevant to all BDD patients (e.g., exposure, response prevention, perceptual retraining) and optional modules to address specific symptoms (e.g., surgery seeking). Thirty-six adults with BDD were randomized to 22 sessions of immediate individual CBT-BDD over 24 weeks (n=17) or to a 12-week waitlist (n=19). The Yale-Brown Obsessive-Compulsive Scale Modified for BDD (BDD-YBOCS), Brown Assessment of Beliefs Scale, and Beck Depression Inventory-II were completed pretreatment, monthly, posttreatment, and at 3- and 6-month follow-up. The Sheehan Disability Scale and Client Satisfaction Inventory (CSI) were also administered. Response to treatment was defined as ≥30% reduction in BDD-YBOCS total from baseline. By week 12, 50% of participants receiving immediate CBT-BDD achieved response versus 12% of waitlisted participants (p=0.026). By posttreatment, 81% of all participants (immediate CBT-BDD plus waitlisted patients subsequently treated with CBT-BDD) met responder criteria. While no significant group differences in BDD symptom reduction emerged by Week 12, by posttreatment CBT-BDD resulted in significant decreases in BDD-YBOCS total over time (d=2.1, p<0.0001), with gains maintained during follow-up. Depression, insight, and disability also significantly improved. Patient satisfaction was high, with a mean CSI score of 87.3% (SD=12.8%) at posttreatment. CBT-BDD appears to be a feasible, acceptable, and efficacious treatment that warrants more rigorous investigation.

Modular cognitive-behavioral therapy for body dysmorphic disorder.

This study pilot tested a newly developed modular cognitive-behavioral therapy (CBT) treatment manual for body dysmorphic disorder (BDD). We tested feasibility, acceptability, and treatment outcome in a sample of 12 adults with primary BDD. Treatment was delivered in weekly individual sessions over 18 or 22 weeks. Standardized clinician ratings and self-report measures were used to assess BDD and related symptoms pre- and posttreatment and at 3- and 6-month follow-ups. At posttreatment, BDD and related symptoms (e.g., mood) were significantly improved. Treatment gains were maintained at follow-up. A relatively low drop-out rate, high patient satisfaction ratings, and patient feedback indicated that the treatment was highly acceptable to patients. To our knowledge, this represents the first test of a broadly applicable, individual psychosocial treatment for BDD.

Body dysmorphic disorder and obsessive–compulsive disorder: similarities, differences and the classification debate

Obsessive–compulsive disorder and body dysmorphic disorder have many similarities in clinical presentation. Obsessive–compulsive disorder has historically been considered an anxiety disorder, whereas body dysmorphic disorder has been grouped among the somatoform disorders. Researchers in these areas are currently debating whether the similarities warrant the inclusion of body dysmorphic disorder within a proposed category of obsessive–compulsive spectrum disorders. This article describes the association between obsessive–compulsive disorder and body dysmorphic disorder as evidenced by the emerging literature, and presents theoretical and clinical implications of this association.

The relationship between anorexia nervosa and body dysmorphic disorder.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are severe body image disorders that highly impair individuals in their daily functioning. They are discrete but overlapping nosological entities. In this review, we examine similarities between AN and BDD with regard to clinical, personality and demographic aspects, such as comorbidity, phenomenology, and treatment outcome. The review suggests that the two disorders are highly comorbid, and show similar ages of onset, illness trajectories, and comparable clinical and personality characteristics. However, important differences emerge in their responsiveness to psychosocial and psychopharmacological treatment, which are discussed. Clinical implications of these findings are summarized and directions for future research are delineated, with a focus on how current treatment components from each disorder may inform new interventions for both disorders.

Dissociable Genetic Contributions to Error Processing: A Multimodal Neuroimaging Study

Background Neuroimaging studies reliably identify two markers of error commission: the error-related negativity (ERN), an event-related potential, and functional MRI activation of the dorsal anterior cingulate cortex (dACC). While theorized to reflect the same neural process, recent evidence suggests that the ERN arises from the posterior cingulate cortex not the dACC. Here, we tested the hypothesis that these two error markers also have different genetic mediation. Methods We measured both error markers in a sample of 92 comprised of healthy individuals and those with diagnoses of schizophrenia, obsessive-compulsive disorder or autism spectrum disorder. Participants performed the same task during functional MRI and simultaneously acquired magnetoencephalography and electroencephalography. We examined the mediation of the error markers by two single nucleotide polymorphisms: dopamine D4 receptor (DRD4) C-521T (rs1800955), which has been associated with the ERN and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), which has been associated with error-related dACC activation. We then compared the effects of each polymorphism on the two error markers modeled as a bivariate response. Results We replicated our previous report of a posterior cingulate source of the ERN in healthy participants in the schizophrenia and obsessive-compulsive disorder groups. The effect of genotype on error markers did not differ significantly by diagnostic group. DRD4 C-521T allele load had a significant linear effect on ERN amplitude, but not on dACC activation, and this difference was significant. MTHFR C677T allele load had a significant linear effect on dACC activation but not ERN amplitude, but the difference in effects on the two error markers was not significant. Conclusions DRD4 C-521T, but not MTHFR C677T, had a significant differential effect on two canonical error markers. Together with the anatomical dissociation between the ERN and error-related dACC activation, these findings suggest that these error markers have different neural and genetic mediation.

Shared social competence impairment: another link between the obsessive-compulsive and autism spectrums?

Recently, there has been a growing interest in the phenotypic, pathogenic, and pathophysiological overlap between autism spectrum disorders (ASD) and obsessive-compulsive spectrum disorders (OCSD). However, social competence impairment is one domain of overlap that has received less attention. Codified as one of three diagnostic categories in ASD, pathological social processing has also been demonstrated in OCSD. Yet, to date no reviews have synthesized the research literature on social competence impairments in OCSD, especially impairments that may parallel those found in ASD. The current review set out to examine the extant literature in this area in the service of advancing understanding of shared phenomenology between these two spectrums of conditions. Further, delineation of shared social competence impairments between ASD and OCSD might highlight candidate endophenotypes for further investigation. Ultimately, understanding the links between OCSD and ASD may aid in development of better intervention and prevention strategies, some of which may directly target maladaptive social processing.

Body dysmorphic symptoms: Phenomenology and ethnicity

Differences in the presentation of clinical features of body dysmorphic disorder (BDD) across ethnic groups have received little investigation. The current study assessed BDD symptoms in an ethnically diverse sample of adults (n=401) using an online survey. Participants completed self-report measures assessing BDD symptoms, body parts of concern and BDD behaviors. Compared to Caucasian participants, no significant differences were found in body parts or behaviors reported by Latino or African American participants. Significant group differences did emerge between Asian and Caucasian participants. Specifically, Asians reported more concern with straight hair and dark skin and fewer body shape concerns than Caucasians. Asians also endorsed lower rates of grooming, touching body parts, and camouflaging and higher rates of exercise compared to Caucasians. Although most clinical features of BDD appear similar across ethnic groups, results showed some differences in body parts and behaviors between Caucasians and Asian Americans with BDD symptoms.

Aberrant error processing in relation to symptom severity in obsessive-compulsive disorder: A multimodal neuroimaging study

BACKGROUND Obsessive-compulsive disorder (OCD) is characterized by maladaptive repetitive behaviors that persist despite feedback. Using multimodal neuroimaging, we tested the hypothesis that this behavioral rigidity reflects impaired use of behavioral outcomes (here, errors) to adaptively adjust responses. We measured both neural responses to errors and adjustments in the subsequent trial to determine whether abnormalities correlate with symptom severity. Since error processing depends on communication between the anterior and the posterior cingulate cortex, we also examined the integrity of the cingulum bundle with diffusion tensor imaging. METHODS Participants performed the same antisaccade task during functional MRI and electroencephalography sessions. We measured error-related activation of the anterior cingulate cortex (ACC) and the error-related negativity (ERN). We also examined post-error adjustments, indexed by changes in activation of the default network in trials surrounding errors. RESULTS OCD patients showed intact error-related ACC activation and ERN, but abnormal adjustments in the post- vs. pre-error trial. Relative to controls, who responded to errors by deactivating the default network, OCD patients showed increased default network activation including in the rostral ACC (rACC). Greater rACC activation in the post-error trial correlated with more severe compulsions. Patients also showed increased fractional anisotropy (FA) in the white matter underlying rACC. CONCLUSIONS Impaired use of behavioral outcomes to adaptively adjust neural responses may contribute to symptoms in OCD. The rACC locus of abnormal adjustment and relations with symptoms suggests difficulty suppressing emotional responses to aversive, unexpected events (e.g., errors). Increased structural connectivity of this paralimbic default network region may contribute to this impairment.

Accept, distract, or reframe? An exploratory experimental comparison of strategies for coping with intrusive body image thoughts in anorexia nervosa and body dysmorphic disorder.

Negative body image is the hallmark of anorexia nervosa (AN) and body dysmorphic disorder (BDD). One aspect of body image, appearance-related thoughts, have shown to be a major contributor to relapse, thus further investigation of successful treatment strategies targeting these maladaptive thoughts are warranted. The present study tested an acceptance/mindfulness (AC), a cognitive restructuring (CR), and a distraction strategy with regard to their short-term effectiveness of reducing the frequency of thought occurrence and associated outcomes in participants with AN (n=20), BDD (n=21), and healthy controls (HC; n=22). Although all strategies led to a significant reduction of thought frequency, there was no group × strategy interaction effect in their reduction. Positive affect increased in the BDD group through the AC strategy, but decreased in healthy controls. Acceptance of the thought increased in the CR strategy in AN, whereas that strategy seemed to work least for BDD. Healthy controls showed most acceptance when using distraction. Taken together, the study suggests that all strategies might have their benefits and that it might be worthwhile further investigating differential indication of the strategies with regard to diagnosis and individual factors.