Untargeted metabolomic analysis of metabolites related to body dysmorphic disorder (BDD).

Body dysmorphic disorder (BDD) is a disorder associated with depression and eating disorders. It often arises from minor defects in appearance or an individual imagining that he or she is defective. However, the mechanisms causing BDD remain unclear, and its pathogenesis and adjuvant treatment methods still need to be explored. Here, we employed a liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach to identify key metabolic differences in BDD versus healthy patients. We obtained plasma samples from two independent cohorts (including eight BDD patients and eight healthy control patients). Raw data were analyzed using Compound Discoverer to determine peak alignment, retention time correction, and extraction of peak areas. Metabolite structure identification was also obtained using Compound Discoverer by of accurate mass matching (< 10 ppm) and secondary spectral matching queries of compound databases. Next, multidimensional statistical analyses were performed using the ropls R package. These analyses included: unsupervised principal component analysis, supervised partial Least-Squares Discriminant Analysis, and orthogonal partial Least-Squares Discriminant Analysis. We then identified the most promising metabolic signatures associated with BDD across all metabolomic datasets. Principal component analysis showed changes in small-molecule metabolites in patients, and we also found significant differences in metabolite abundance between the BDD and normal groups. Our findings suggest that the occurrence of BDD may be related to metabolites participating in the following KEGG pathways: ABC transporters, purine metabolism, glycine, serine and threonine metabolism, pyrimidine, pyrimidine metabolism, biosynthesis of 12-, 14-, and 16-membered macrolides, microbial metabolism in diverse environments, biosynthesis of secondary metabolites, and caffeine and insect hormone biosynthesis.

Serum oxytocin levels are elevated in body dysmorphic disorder and related to severity of psychopathology.

The neurobiological mechanisms underlying the pathophysiology of body dysmorphic disorder (BDD) are not well-understood. Oxytocin is a central nervous system peptide which regulates socioemotional functioning and may mediate physiologic processes in a range of psychiatric disorders, particularly those characterized by interpersonal dysfunction. Examining the role of oxytocin in the development and maintenance of BDD may elucidate new targets for intervention. The present study examined endogenous serum oxytocin levels in BDD. Given the prominent deficits in social functioning in BDD, we expected that BDD would be characterized by low basal serum oxytocin concentrations, relative to healthy controls, and that low oxytocin levels would be associated with BDD symptom severity as well as poor performance on measures of social cognition. Twenty individuals with BDD and 28 healthy controls completed a fasting blood draw consisting of frequent sampling every five minutes for one hour to measure pooled levels of oxytocin. Contrary to our hypotheses, people with BDD displayed higher concentrations of oxytocin, compared to their healthy control counterparts, and their oxytocin levels were positively correlated with BDD symptom severity. There were no associations between oxytocin levels and measures of social cognition. These findings suggest increased production of endogenous oxytocin in BDD. Prospective research is needed to determine whether this contributes to or is a consequence of BDD symptomatology.

Alterations in serotonin transporter and body image-related cognition in anorexia nervosa.

The serotonin system has been implicated in the pathophysiology of anorexia nervosa (AN). A recent report proposed that body image distortion (BID), a core symptom of AN, may relate to abnormalities of the serotonin system, especially the serotonin transporter (5HTT). Positron emission tomography (PET) studies of underweight patients with active AN reported alterations in serotonin receptors, but not 5HTT. Here, we aimed to disclose the clinicopathophysiology of AN by focusing on 5HTT and cognitive functions, including BID, in groups with active AN. Twenty-two underweight female patients with AN (12 restricting-type AN (ANR); 10 binge-eating/purging-type AN (ANBP)) and 20 age-matched healthy female subjects underwent PET with a 5HTT radioligand [11C]DASB. The binding potential (BPND) of [11C]DASB was estimated semiquantitatively, and clinical data from Raven's colored progressive matrices for general intelligence, the Stroop test for focused attention, the Iowa gambling task for decision making and a dot-probe task designed for BID were compared with the levels of BPND in different groups. [11C]DASB BPND was significantly decreased in the medial parietal cortex in patients with AN and in the dorsal raphe in patients with ANR compared with healthy subjects (p < .05 corrected). Patients with ANR showed a significantly negative correlation between [11C]DASB BPND in the dorsal raphe and performance on the dot-probe task (p < .05 corrected). While reduced 5HTT in the medial parietal cortex (the somatosensory association area) is pathophysiologically important in AN in general, additional 5HTT reduction in the dorsal raphe as seen in ANR is implicated for the clinicopathophysiological relevance.

Abnormal brain network organization in body dysmorphic disorder.

Body dysmorphic disorder (BDD) is characterized by preoccupation with misperceived defects of appearance, causing significant distress and disability. Previous studies suggest abnormalities in information processing characterized by greater local relative to global processing. The purpose of this study was to probe whole-brain and regional white matter network organization in BDD, and to relate this to specific metrics of symptomatology. We acquired diffusion-weighted 34-direction MR images from 14 unmedicated participants with DSM-IV BDD and 16 healthy controls, from which we conducted whole-brain deterministic diffusion tensor imaging tractography. We then constructed white matter structural connectivity matrices to derive whole-brain and regional graph theory metrics, which we compared between groups. Within the BDD group, we additionally correlated these metrics with scores on psychometric measures of BDD symptom severity as well as poor insight/delusionality. The BDD group showed higher whole-brain mean clustering coefficient than controls. Global efficiency negatively correlated with BDD symptom severity. The BDD group demonstrated greater edge betweenness centrality for connections between the anterior temporal lobe and the occipital cortex, and between bilateral occipital poles. This represents the first brain network analysis in BDD. Results suggest disturbances in whole brain structural topological organization in BDD, in addition to correlations between clinical symptoms and network organization. There is also evidence of abnormal connectivity between regions involved in lower-order visual processing and higher-order visual and emotional processing, as well as interhemispheric visual information transfer. These findings may relate to disturbances in information processing found in previous studies.

Trastornos somatomorfos y depresión / Somatomorphic disorders and depression

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High-dose glycine treatment of refractory obsessive-compulsive disorder and body dysmorphic disorder in a 5-year period.

This paper describes an individual who was diagnosed with obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) at age 17 when education was discontinued. By age 19, he was housebound without social contacts except for parents. Adequate trials of three selective serotonin reuptake inhibitors, two with atypical neuroleptics, were ineffective. Major exacerbations following ear infections involving Group A beta-hemolytic streptococcus at ages 19 and 20 led to intravenous immune globulin therapy, which was also ineffective. At age 22, another severe exacerbation followed antibiotic treatment for H. pylori. This led to a hypothesis that postulates deficient signal transduction by the N-methyl-D-aspartate receptor (NMDAR). Treatment with glycine, an NMDAR coagonist, over 5 years led to robust reduction of OCD/BDD signs and symptoms except for partial relapses during treatment cessation. Education and social life were resumed and evidence suggests improved cognition. Our findings motivate further study of glycine treatment of OCD and BDD.