Jamie D. Feusner

Abnormalities of Visual Processing and Frontostriatal Systems in Body Dysmorphic Disorder

CONTEXT Body dysmorphic disorder (BDD) is a psychiatric disorder in which individuals are preoccupied with perceived defects in their appearance, often related to their face. Little is known about its pathophysiology, although early research provides evidence of abnormal visual processing. OBJECTIVE To determine whether patients with BDD have abnormal patterns of brain activation when visually processing their own face with high, low, or normal spatial resolution. DESIGN Case-control study. SETTING A university hospital. PARTICIPANTS Seventeen right-handed medication-free subjects with BDD and 16 matched healthy control subjects. Intervention Functional magnetic resonance imaging while viewing photographs of face stimuli. Stimuli were neutral-expression photographs of the patients own face and a familiar face (control stimuli) that were unaltered, altered to include only high spatial frequency (fine spatial resolution), or altered to include only low spatial frequency (low spatial resolution). MAIN OUTCOME MEASURE Blood oxygen level-dependent signal changes in the BDD and control groups during each stimulus type. RESULTS Subjects with BDD showed relative hyperactivity in the left orbitofrontal cortex and bilateral head of the caudate for the unaltered own-face vs familiar-face condition. They showed relative hypoactivity in the left occipital cortex for the low spatial frequency faces. Differences in activity in frontostriatal systems but not visual cortex covaried with aversiveness ratings of the faces. Severity of BDD symptoms correlated with activity in frontostriatal systems and visual cortex. CONCLUSIONS These results suggest abnormalities in visual processing and frontostriatal systems in BDD. Hypoactivation in the occipital cortex for low spatial frequency faces may indicate either primary visual system abnormalities for configural face elements or top-down modulation of visual processing. Frontostriatal hyperactivity may be associated both with aversion and with symptoms of obsessive thoughts and compulsive behaviors.

Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses.

BACKGROUND This represents the first graph theory-based brain network analysis study in bipolar disorder, a chronic and disabling psychiatric disorder characterized by severe mood swings. Many imaging studies have investigated white matter in bipolar disorder, with results suggesting abnormal white matter structural integrity, particularly in the fronto-limbic and callosal systems. However, many inconsistencies remain in the literature, and no study to date has conducted brain network analyses with a graph-theoretic approach. METHODS We acquired 64-direction diffusion-weighted magnetic resonance imaging on 25 euthymic bipolar I disorder subjects and 24 gender- and age-equivalent healthy subjects. White matter integrity measures including fractional anisotropy and mean diffusivity were compared in the whole brain. Additionally, structural connectivity matrices based on whole-brain deterministic tractography were constructed, followed by the computation of both global and local brain network measures. We also designed novel metrics to further probe inter-hemispheric integration. RESULTS Network analyses revealed that the bipolar brain networks exhibited significantly longer characteristic path length, lower clustering coefficient, and lower global efficiency relative to those of control subjects. Further analyses revealed impaired inter-hemispheric but relatively preserved intra-hemispheric integration. These findings were supported by whole-brain white matter analyses that revealed significantly lower integrity in the corpus callosum in bipolar subjects. There were also abnormalities in nodal network measures in structures within the limbic system, especially the left hippocampus, the left lateral orbitofrontal cortex, and the bilateral isthmus cingulate. CONCLUSIONS These results suggest abnormalities in structural network organization in bipolar disorder, particularly in inter-hemispheric integration and within the limbic system.

Antidepressants and suicidal behaviour in unipolar depression

Objective:  To compare the rates of suicidal behaviour during vs. after discontinuation of treatment with antidepressants, and to determine the comparative rates of suicidal behaviour for patients maintained on tricyclic (TCA) vs. selective serotonin reuptake inhibitor (SSRI) antidepressants.

GABAA receptor β3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population

GABAergic systems have been implicated in the pathogenesis of anxiety, depression and insomnia. These symptoms are part of the core and comorbid psychiatric disturbances in post-traumatic stress disorder (PTSD). In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GABA(A) receptor beta 3 subunit gene were compared to scores on the General Health Questionnaire-28 (GHQ). As the major allele at this gene locus (GABRB3) was G1, the alleles were divided into G1 and non-G1 groups. On the total score of the GHQ, which comprises the somatic symptoms, anxiety/insomnia, social dysfunction and depression subscales, patients with the G1 non-G1 genotype had a significantly higher score when compared to either the G1G1 genotype (alpha=0.01) or the non-G1 non-G1 genotype (alpha=0.05). No significant difference was found between the G1G1 and non-G1 non-G1 genotypes. When the G1 non-G1 heterozygotes were compared to the combined G1G1 and non-G1 non-G1 homozygotes, a significantly higher total GHQ score was found in the heterozygotes (P=0.002). These observations suggest a heterosis effect. Further analysis of GHQ subscale scores showed that heterozygotes compared to the combined homozygotes had higher scores on the somatic symptoms (P=0.006), anxiety/insomnia (P=0.003), social dysfunction (P=0.054) and depression (P=0.004) subscales. In conclusion, the present study indicates that in a population of PTSD patients, heterozygosity of the GABRB3 major (G1) allele confers higher levels of somatic symptoms, anxiety/insomnia, social dysfunction and depression than found in homozygosity.

A Pilot Study of Rhodiola rosea (Rhodax®) for Generalized Anxiety Disorder (GAD)

BACKGROUND Rhodiola rosea is an herbal supplement that many in the general population in Russia and elsewhere in the world have used for decades to alleviate everyday anxiety, depression, and insomnia. Whether R. rosea is effective in reducing similar symptoms in clinical samples is unknown. The goal of this pilot study was to evaluate whether R. rosea is effective in reducing symptoms of generalized anxiety disorder (GAD). METHOD Ten (10) participants with a DSM-IV diagnosis of GAD, recruited from the UCLA Anxiety Disorders Program and between the ages of 34 and 55, were enrolled in this study from November 2005 to May 2006. Participants received a total daily dose of 340 mg of R. rosea extract for 10 weeks. Assessments included the Hamilton Anxiety Rating Scale (HARS), the Four-Dimensional Anxiety and Depression Scale, and the Clinical Global Impressions of Severity/Improvement Scale. RESULTS Individuals treated with R. rosea showed significant decreases in mean HARS scores at endpoint (t=3.27, p=0.01). Adverse events were generally mild or moderate in severity, the most common being dizziness and dry mouth. CONCLUSIONS Significant improvement in GAD symptoms was found with R. rosea, with a reduction in HARS scores similar to that found in clinical trials. These preliminary findings warrant further exploration of treatment with R. rosea in clinical samples.

Abnormalities of object visual processing in body dysmorphic disorder.

BACKGROUND Individuals with body dysmorphic disorder (BDD) may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with BDD have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. METHOD Fourteen medication-free participants with DSM-IV BDD and 14 healthy controls participated. We performed functional magnetic resonance imaging (fMRI) while participants matched photographs of houses that were unaltered, contained only high spatial frequency (HSF, high detail) information or only low spatial frequency (LSF, low detail) information. The primary outcome was group differences in blood oxygen level-dependent (BOLD) signal changes. RESULTS The BDD group showed lower activity in the parahippocampal gyrus, lingual gyrus and precuneus for LSF images. There were greater activations in medial prefrontal regions for HSF images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lower activity in the dorsal occipital cortex and ventrolateral prefrontal cortex for normal spatial frequency (NSF) and HSF images. CONCLUSIONS Individuals with BDD have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details are consistent with a model of imbalances in global versus local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms.

Regional brain volumes and symptom severity in body dysmorphic disorder

Body dysmorphic disorder (BDD) is a severe psychiatric condition in which individuals are preoccupied with perceived defects in their appearance. Little is known of the pathophysiology or neurobiology of BDD. Recent evidence from a functional MRI study examining visual processing of faces demonstrated abnormal activation patterns in regions including left-sided inferior frontal gyrus (IFG) and amygdala. To investigate morphometric abnormalities, we compared brain volumes from high-resolution T1 magnetic resonance images of 12 unmedicated subjects with BDD to images of 12 matched controls using voxel-based morphometry (VBM). In addition, we compared volumes in specific regions of interest including the IFG, amygdala, caudate, and total grey and white matter and examined correlations with symptom severity. VBM revealed no statistically significant volumetric differences, nor were there significant differences in any of the regions of interest. However, there were significant positive correlations between scores on the BDD version of the Yale-Brown Obsessive-Compulsive Disorder Scale (BDD-YBOCS) and volumes of the left IFG (r=0.69) and the right amygdala (r=0.54). These findings of correlations between BDD symptom severity and volumes of the left IFG and the right amygdala. These are in concordance with the involvement of these regions in pathological face processing, which may contribute to the primary symptomatology.

Altered interoceptive awareness in anorexia nervosa: Effects of meal anticipation, consumption and bodily arousal

OBJECTIVE Impaired interoceptive awareness (IA), the subjective perception of internal body sensations, has been proposed as a vulnerability or maintaining factor in anorexia nervosa (AN). We examined whether IA of heartbeat and breathing sensations was impaired in AN across a range of arousal levels, and whether it was influenced by meal anticipation and consumption. METHOD IA was assessed using randomized, double-blinded, bolus intravenous infusions of isoproterenol, a peripheral beta-adrenergic sympathetic agonist, and saline. Fifteen women with AN and 15 age-, and sex- matched healthy comparisons (HC) were evaluated before and after consumption of a 1,000 Calorie meal. During each infusion participants rated their moment-to-moment intensity of heartbeat and breathing sensations with a dial. To measure IA we evaluated interoceptive detection thresholds, retrospective ratings of palpitation and dyspnea intensity, and interoceptive accuracy via correlations between subjective dial ratings and observed heart rate responses. RESULTS Contrary to prediction the AN group was more likely to report detection of interoceptive sensations across all conditions, an effect driven by false discriminations at low arousal levels. Concordant with prediction, meal anticipation was associated with intensified interoceptive sensations, particularly dyspnea. There were no differences in interoceptive accuracy. DISCUSSION This represents the first demonstration of interoceptive prediction errors in AN. Although IA is unimpaired at high arousal levels in AN, prediction signals are abnormal at low arousal levels, especially during meal anticipation. Altered interoceptive prediction signaling during meal anticipation could contribute to phenotypes of high anxiety in AN or alternatively, might be explained by enhanced meal associated anxiety.

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.

The pathophysiology of body dysmorphic disorder

Body dysmorphic disorder (BDD) is an often severe and disabling condition, affecting up to 2% of the population. Despite its prevalence and clinical significance, very little is known about the pathophysiology of BDD. However, clues to its possible neurobiological substrates and abnormalities in information processing are starting to emerge. This article reviews findings from genetic, brain lesion, neuroimaging, neuropsychological, and psychopharmacological studies that have allowed us to develop a tentative model of the functional neuroanatomy of BDD. There is likely a complex interplay of dysfunctions in several brain networks underlying the pathophysiology of BDD. A combination of dysfunctions in frontal-subcortical circuits, temporal, parietal, and limbic structures, and possibly involving hemispheric imbalances in information processing, may produce both the characteristic symptoms and neurocognitive deficits seen in BDD. An improved understanding of the pathophysiology of BDD will be crucial to guide the development of better treatments.