Concept: Body dysmorphic disorder
Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 × 10(-11)) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.
Orthorexia nervosa describes a pathological obsession with proper nutrition that is characterized by a restrictive diet, ritualized patterns of eating, and rigid avoidance of foods believed to be unhealthy or impure. Although prompted by a desire to achieve optimum health, orthorexia may lead to nutritional deficiencies, medical complications, and poor quality of life. Despite its being a distinct behavioral pattern that is frequently observed by clinicians, orthorexia has received very little empirical attention and is not yet formally recognized as a psychiatric disorder. In this review, we synthesize existing research to identify what is known about the symptoms, prevalence, neuropsychological profile, and treatment of orthorexia. An examination of diagnostic boundaries reveals important points of symptom overlap between orthorexia and anorexia nervosa, obsessive-compulsive disorder (OCD), obsessive-compulsive personality disorder (OCPD), somatic symptom disorder, illness anxiety disorder, and psychotic spectrum disorders. Neuropsychological data suggest that orthorexic symptoms are independently associated with key facets of executive dysfunction for which some of these conditions already overlap. Discussion of cognitive weaknesses in set-shifting, external attention, and working memory highlights the value of continued research to identify intermediate, transdiagnostic endophenotypes for insight into the neuropathogenesis of orthorexia. An evaluation of current orthorexia measures indicates a need for further psychometric development to ensure that subsequent research has access to reliable and valid assessment tools. Optimized assessment will not only permit a clearer understanding of prevalence rates, psychosocial risk factors, and comorbid psychopathology but will also be needed to index intervention effectiveness. Though the field lacks data on therapeutic outcomes, current best practices suggest that orthorexia can successfully be treated with a combination of cognitive-behavioral therapy, psychoeducation, and medication.
Social media use is ever increasing amongst young adults and has previously been shown to have negative effects on body image, depression, social comparison, and disordered eating. One eating disorder of interest in this context is orthorexia nervosa, an obsession with eating healthily. High orthorexia nervosa prevalence has been found in populations who take an active interest in their health and body and is frequently comorbid with anorexia nervosa. Here, we investigate links between social media use, in particularly Instagram and orthorexia nervosa symptoms.
Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and severe mental illnesses of unknown etiology. Recently, we identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) that is associated with the development of eating disorders. However, little is known about ESRRA function in the brain. Here, we report that Esrra is expressed in the mouse brain and demonstrate that Esrra levels are regulated by energy reserves. Esrra-null female mice display a reduced operant response to a high-fat diet, compulsivity/behavioral rigidity, and social deficits. Selective Esrra knockdown in the prefrontal and orbitofrontal cortices of adult female mice recapitulates reduced operant response and increased compulsivity, respectively. These results indicate that Esrra deficiency in the mouse brain impairs behavioral responses in multiple functional domains.
Background. In recent years, there has been an explosion in the number of technical and medical diagnostic platforms being developed. This has greatly improved our ability to more accurately, and more comprehensively, explore and characterize human biological systems on the individual level. Large quantities of biomedical data are now being generated and archived in many separate research and clinical activities, but there exists a paucity of studies that integrate the areas of clinical neuropsychiatry, personal genomics and brain-machine interfaces. Methods. A single person with severe mental illness was implanted with the Medtronic Reclaim(®) Deep Brain Stimulation (DBS) Therapy device for Obsessive Compulsive Disorder (OCD), targeting his nucleus accumbens/anterior limb of the internal capsule. Programming of the device and psychiatric assessments occurred in an outpatient setting for over two years. His genome was sequenced and variants were detected in the Illumina Whole Genome Sequencing Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Results. We report here the detailed phenotypic characterization, clinical-grade whole genome sequencing (WGS), and two-year outcome of a man with severe OCD treated with DBS. Since implantation, this man has reported steady improvement, highlighted by a steady decline in his Yale-Brown Obsessive Compulsive Scale (YBOCS) score from ∼38 to a score of ∼25. A rechargeable Activa RC neurostimulator battery has been of major benefit in terms of facilitating a degree of stability and control over the stimulation. His psychiatric symptoms reliably worsen within hours of the battery becoming depleted, thus providing confirmatory evidence for the efficacy of DBS for OCD in this person. WGS revealed that he is a heterozygote for the p.Val66Met variant in BDNF, encoding a member of the nerve growth factor family, and which has been found to predispose carriers to various psychiatric illnesses. He carries the p.Glu429Ala allele in methylenetetrahydrofolate reductase (MTHFR) and the p.Asp7Asn allele in ChAT, encoding choline O-acetyltransferase, with both alleles having been shown to confer an elevated susceptibility to psychoses. We have found thousands of other variants in his genome, including pharmacogenetic and copy number variants. This information has been archived and offered to this person alongside the clinical sequencing data, so that he and others can re-analyze his genome for years to come. Conclusions. To our knowledge, this is the first study in the clinical neurosciences that integrates detailed neuropsychiatric phenotyping, deep brain stimulation for OCD and clinical-grade WGS with management of genetic results in the medical treatment of one person with severe mental illness. We offer this as an example of precision medicine in neuropsychiatry including brain-implantable devices and genomics-guided preventive health care.
Body dysmorphic disorder (BDD) is a debilitating disorder characterized by an excessive pre-occupation with an imagined or very slight defect in one’s physical appearance. Despite the overall success of cognitive behavioural therapy (CBT) in treating BDD, some people do not seem to benefit as much from this approach. Those with high overvalued ideation (OVI), for instance, have been shown to not respond well with CBT. The purpose of this study was to evaluate the efficacy of an inference-based therapy (IBT) in treating BDD. IBT is a cognitive intervention that was first developed for obsessive-compulsive disorder with high OVI, but whose focus on beliefs can also apply to a BDD population. IBT conceptualizes BDD obsessions (e.g., ‘I feel like my head is deformed’) as idiosyncratic inferences arrived at through inductive reasoning processes. Such primary inferences represent the starting point of obsessional doubt and the treatment focuses on addressing the faulty inferences that maintain the doubt. Thirteen BDD participants, of whom 10 completed, underwent a 20-week IBT for BDD. The participants improved significantly over the course of therapy, with large diminutions in BDD and depressive symptoms. OVI also decreased throughout therapy and was not found to be related to reduction in BDD symptoms. Although a controlled-trial comparing CBT with IBT is needed, it is proposed that IBT constitutes a promising treatment alternative for BDD especially in cases where OVI is high. Copyright © 2011 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: An inference-based therapy (IBT) may be effective in treating BDD. Unlike CBT, in IBT, overvalued ideation does not appear to negatively impact decrease in BDD symptomatology.
Previous research in eating disorders suggests that treatment satisfaction is closely related to the manner in which care is delivered. The present research is a systematic in depth study of health professional characteristics preferred by AN-patients.
Background: Deep brain stimulation (DBS) has emerged in recent years as a novel therapy in the treatment of refractory psychiatric disease, including major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and Tourette’s syndrome (TS). Standardized outcome scales were crucial in establishing that DBS was an effective therapy for movement disorders. Objective: In order to better characterize the evidence supporting DBS for various psychiatric diseases, we performed a pooled analysis of those studies which incorporated specific standardized rating scales. Methods: A Medline search was conducted to identify all studies reporting DBS for MDD, OCD, and TS. The search yielded a total of 49 articles, of which 24 were included: 4 related to MDD (n = 48), 10 to OCD (n = 64), and 10 to TS (n = 46). Results: A meta-analysis of DBS for MDD, OCD, and TS in studies employing disease-specific standardized outcome scales showed that the outcome scales all improved in a statistically significant fashion for these psychiatric diseases. Our pooled analysis suggests that DBS for TS has the highest efficacy amongst the psychiatric diseases currently being treated with DBS, followed by OCD and MDD. Conclusion: DBS for psychiatric diseases remains investigational; however, even when studies failing to incorporate standardized outcome scales are excluded, there is statistically significant evidence that DBS can improve symptoms in MDD, OCD, and TS. Standardized disease-specific outcome scales facilitate pooled analysis and should be a required metric in future studies of DBS for psychiatric disease. © 2013 S. Karger AG, Basel.
Family based-treatments have the most empirical support in the treatment of adolescent anorexia nervosa; yet, a significant percentage of adolescents and their families do not respond to manualized family based treatment (FBT). The aim of this open trial was to conduct a preliminary evaluation of an innovative family-based approach to the treatment of anorexia: Acceptance-based Separated Family Treatment (ASFT). Treatment was grounded in Acceptance and Commitment Therapy (ACT), delivered in a separated format, and included an ACT-informed skills program. Adolescents (ages 12-18) with anorexia or sub-threshold anorexia and their families received 20 treatment sessions over 24 weeks. Outcome indices included eating disorder symptomatology reported by the parent and adolescent, percentage of expected body weight achieved, and changes in psychological acceptance/avoidance. Half of the adolescents (48.0%) met criteria for full remission at the end of treatment, 29.8% met criteria for partial remission, and 21.3% did not improve. Overall, adolescents had a significant reduction in eating disorder symptoms and reached expected body weight. Treatment resulted in changes in psychological acceptance in the expected direction for both parents and adolescents. This open trial provides preliminary evidence for the feasibility, acceptability, and efficacy of ASFT for adolescents with anorexia. Directions for future research are discussed.
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has commonly been described in psychiatric disorders. Although several studies have found positive associations between abnormal eating patterns during childhood and ADHD, there is a lack of studies on ADHD and Eating Disorders (ED). The aims of this exploratory study were 1) to assess the ADHD symptoms level in ED and to ascertain whether there are differences among ED subtypes; 2) to analyze whether the presence of ADHD symptoms is associated with more severe eating disorder symptoms and greater general psychopathology; and 3) to assess whether the ADHD symptoms level is associated with specific temperament and character traits. METHODS: 191 female ED patients were included. Assessment was carried out with the EDI-2, ASRS-v1.1, the SCL-90-R and the TCI-R. RESULTS: The ADHD symptoms level was similar in bulimia, eating disorder not otherwise specified and binge eating subtypes, and lower in anorexic patients. Obsessiveness and Hostility were significantly positively associated with ADHD symptoms. A path model showed that ADHD was associated with high Novelty Seeking and low Self-Directedness, whereas ED severity was influenced by ADHD severity and low Self-Directedness. CONCLUSIONS: Bingeing/purging ED subtypes have a high ADHD symptoms level, also related with more severe eating, general and personality psychopathology.