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Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals ("Member Advocates") who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment. [ABSTRACT FROM AUTHOR]

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals ("Member Advocates") who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment. [ABSTRACT FROM AUTHOR]

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Behavioral features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN. Methods: In this brain imaging study, 29 female adolescents with partially or fully weight‐restored AN and 27 healthy controls, all between 10 and 19 years, underwent whole‐brain multi‐shell diffusion tensor imaging. Utilizing neurite orientation dispersion and density imaging methods, we investigated group differences in white matter neurite density, orientation dispersion, and myelin density in tracts between prominent nodes of the reward circuit (ventral tegmental area (VTA) to nucleus accumbens (NAcc)) and the habit circuit (sensory motor area [SMA] to putamen). Results: Findings revealed reduced neurite (F = 5.20, p = 0.027) and myelin density (F = 5.39, p = 0.025) in the left VTA‐NAcc tract, and reduced orientation dispersion in the left (F = 7.00, p = 0.011) and right (F = 6.77, p = 0.012) VTA‐NAcc tract. There were no significant group differences in the SMA‐putamen tract. Significant relationships, after corrections, were not evident between tract microstructure and reward responsiveness, compulsive behaviors, illness duration, or BMI. Conclusions: Adolescents with AN exhibit less dense, undermyelinated, and less dispersed white matter tracts connecting prominent reward system nodes, which could potentially signify underutilization of this part of the reward circuit. These results provide a detailed examination of white matter microstructure in tracts underlying instrumental behavioral phenotypes contributing to illness in AN. [ABSTRACT FROM AUTHOR]

Background: Clinical use of psychedelics has gained considerable attention, with promising benefits across a range of mental disorders. Current pharmacological and psychotherapeutic treatments for body dysmorphic disorder (BDD) and eating disorders (EDs) have limited efficacy. As such, other treatment options such as psychedelic-assisted therapies are being explored in these clinical groups. Aims: This systematic review evaluates evidence related to the therapeutic potential of psychedelics in individuals diagnosed with BDD and EDs. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review of all study designs published to the end of February 2022 that identified changes in ED/BDD symptom severity from psychedelics using validated measures to assess symptom changes. Results: Our search detected a total of 372 studies, of which five met inclusion criteria (two exploratory studies, two case reports, and one prospective study). These were included in the data evaluation. Effects of psychedelics on BDD and various ED symptoms were identified mostly through thematic analyses and self-reports. Conclusions: Our findings highlight that more research is needed to determine the safety and efficacy of psychedelics in BDD and EDs and we suggest avenues for future exploration. [ABSTRACT FROM AUTHOR]

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders (BDDs), studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associated with hyperconnectivity in the default mode network (DMN) in self-focused patients with these disorders. Thirty patients with primary social anxiety disorder or primary BDD and 28 healthy individuals were eligible and scanned. Eligibility was determined by scoring greater than 1SD or below 1SD of the Public Self-Consciousness Scale normative mean, respectively, for each group. Seed-to-voxel functional connectivity was computed using a DMN posterior cingulate cortex (PCC) seed. There was no evidence of increased DMN functional connectivity in patients compared to controls. Patients (regardless of diagnosis) showed reduced functional connectivity of the PCC with several brain regions, including the bilateral superior parietal lobule (SPL), compared to controls, which was inversely correlated with maladaptive SFA but not associated with social anxiety, body dysmorphic, depression severity or rumination. Abnormal PCC-SPL connectivity may represent a transdiagnostic neural marker of SFA that reflects difficulty shifting between internal versus external attention. [ABSTRACT FROM AUTHOR]

In individuals with body dysmorphic disorder (BDD), perceptual appearance distortions may be related to imbalances in global vs. local visual processing. Understanding the mechanistic brain effects of potential interventions is crucial for rational treatment development. The dorsal visual stream (DVS) is tuned to rapid image presentation, facilitating global/holistic processing, whereas the ventral visual stream (VVS), responsible for local/detailed processing, reduces activation magnitude with shorter stimulus duration. This study tested a strategy of rapid, short-duration face presentation on visual system connectivity. Thirty-eight unmedicated adults with BDD and 29 healthy controls viewed photographs of their faces for short (125 ms, 250 ms, 500 ms) and long (3000 ms) durations during fMRI scan. Dynamic effective connectivity in DVS and VVS was analyzed. BDD individuals exhibited weaker connectivity from occipital to parietal DVS areas than controls for all stimuli durations. Short compared with long viewing durations (125 ms vs. 3,000 ms and 500 ms vs. 3,000 ms) resulted in significantly weaker VVS connectivity from calcarine cortex to inferior occipital gyri in controls; however, there was only a trend for similar results in BDD. The DVS to VVS ratio, representing a balance between global and local processing, incrementally increased with shorter viewing durations in BDD, although it was not statistically significant. In sum, visual systems in those with BDD are not as responsive as in controls to rapid face presentation. Whether rapid face presentation could reduce connectivity in visual systems responsible for local/detailed processing in BDD may necessitate different parameters or strategies. These results provide mechanistic insights for perceptual retraining treatment designs. [ABSTRACT FROM AUTHOR]

Background: Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations—a critical component of hedonic responding—has never been studied in AN. Methods: This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12–22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired. Discussion: This study will be the first to interrogate appetitive conditioning in AN—a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward. Trial registration: Pending. Intended registry: Clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition. [ABSTRACT FROM AUTHOR]

As current psychosocial and pharmacological interventions show limited efficacy in the treatment of anorexia nervosa (AN), interest in the potential value of neurosurgical intervention and neuromodulation in managing severe and enduring illness has grown. We conducted a systematic review of 20 trials of neurosurgical and neuromodulatory treatments for AN, including neurosurgical ablation, deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, there is evidence to support the role of stereotactic ablation and DBS in the treatment of AN. In contrast, results for rTMS and tDCS have been modest and generally more mixed. Neurosurgical treatment may offer important new avenues for the treatment of AN. Additional randomized clinical trials with comparable patient populations will be needed, in which change in affective, cognitive, and perceptual symptom phenomena, and interrogation of targeted circuits, pre- and post-intervention, are carefully documented. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships. [ABSTRACT FROM AUTHOR]

Body image disturbance (BID) is a core feature of eating disorders, for which there are few objective markers. We examined the feasibility of a novel digital tool, "Somatomap", to index BID related to anorexia nervosa (AN) severity. Fifty-five AN inpatients and 55 healthy comparisons (HC) outlined their body concerns on a 2-Dimensional avatar. Next, they indicated sizes/shapes of body parts for their current and ideal body using sliders on a 3-Dimensional avatar. Physical measurements of corresponding body parts, in cm, were collected for reference. We evaluated regional differences in BID using proportional z-scores to generate statistical body maps, and multivariate analysis of covariance to assess perceptual discrepancies for current body, ideal body, and body dissatisfaction. The AN group demonstrated greater regional perceptual inaccuracy for their current body than HC, greater discrepancies between their current and ideal body, and higher body dissatisfaction than HCs. AN body concerns localized disproportionately to the chest and lower abdomen. The number of body concerns and perceptual inaccuracy for individual body parts was strongly associated with Eating Disorder Examination Questionnaire (Global EDE-Q) scores across both groups. Somatomap demonstrated feasibility to capture multidimensional aspects of BID. Several implicit measures were significantly associated with illness severity, suggesting potential utility for identifying objective BID markers. [ABSTRACT FROM AUTHOR]

The hemodynamic response function (HRF) represents the transfer function linking neural activity with the functional MRI (fMRI) signal, modeling neurovascular coupling. Since HRF is influenced by non-neural factors, to date it has largely been considered as a confound or has been ignored in many analyses. However, underlying biophysics suggests that the HRF may contain meaningful correlates of neural activity, which might be unavailable through conventional fMRI metrics. Here, we estimated the HRF by performing deconvolution on resting-state fMRI data from a longitudinal sample of 25 healthy controls scanned twice and 44 adults with obsessive-compulsive disorder (OCD) before and after 4-weeks of intensive cognitive-behavioral therapy (CBT). HRF response height, time-to-peak and full-width at half-maximum (FWHM) in OCD were abnormal before treatment and normalized after treatment in regions including the caudate. Pre-treatment HRF predicted treatment outcome (OCD symptom reduction) with 86.4% accuracy, using machine learning. Pre-treatment HRF response height in the caudate head and time-to-peak in the caudate tail were top-predictors of treatment response. Time-to-peak in the caudate tail, a region not typically identified in OCD studies using conventional fMRI activation or connectivity measures, may carry novel importance. Additionally, pre-treatment response height in caudate head predicted post-treatment OCD severity (R = -0.48, P = 0.001), and was associated with treatment-related OCD severity changes (R = -0.44, P = 0.0028), underscoring its relevance. With HRF being a reliable marker sensitive to brain function, OCD pathology, and intervention-related changes, these results could guide future studies towards novel discoveries not possible through conventional fMRI approaches like standard BOLD activation or connectivity. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared AN and BDD in brain activation and connectivity in relevant networks when viewing images of others' bodies and tested their relationships with clinical symptoms and subjective appearance evaluations. We acquired fMRI data from 64 unmedicated females (20 weight-restored AN, 23 BDD, 21 controls) during a matching task using unaltered or spatial-frequency filtered photos of others' bodies. Using general linear model and independent components analyses we compared brain activation and connectivity in visual, striatal, and parietal networks and performed univariate and partial least squares multivariate analyses to investigate relationships with clinical symptoms and appearance evaluations. AN and BDD showed partially overlapping patterns of hyperconnectivity in the dorsal visual network and hypoconnectivity in parietal network compared with controls. BDD, but not AN, demonstrated hypoactivity in dorsal visual and parietal networks compared to controls. Further, there were significant activity and connectivity differences between AN and BDD in both networks. In both groups, activity and/or connectivity were associated with symptom severity and appearance ratings of others' bodies. Thus, AN and BDD demonstrate both distinct and partially-overlapping aberrant neural phenotypes involved in body processing and visually encoding global features. Nevertheless, in each disorder, aberrant activity and connectivity show relationships to clinically relevant symptoms and subjective perception. These results have implications for understanding distinct and shared pathophysiology underlying perceptual distortions of appearance and may inform future novel treatment strategies. [ABSTRACT FROM AUTHOR]

Eating disorder and body dysmorphic disorder symptoms overlap and frequently co-occur clinically, yet whether they represent one or more underlying constructs in the general population is unknown. We examined relationships between these symptoms on underlying factor structures and dimensional distributions in a young adult sample of 328 students using the Eating Disorder Examination-Questionnaire (EDE-Q 6.0) and the Dysmorphic Concern Questionnaire (DCQ). We performed factor and hierarchical cluster analyses on pooled items and Gaussian mixture modeling on score distributions. EDE-Q 6.0 and DCQ total scores were correlated (r = 0.53, p <.001). Pooled items demonstrated a three-factor solution; DCQ items separating from two EDE-Q 6.0 factors. Hierarchical clustering yielded a two-cluster solution that separated the two scales. Mixture modeling demonstrated that more than one underlying distribution best fit the data for each scale. These results suggest that the EDE-Q 6.0 and DCQ measure different sets of psychopathological features, despite their tendency to track together. Moreover, eating disorder and body dysmorphic phenotypes each show nonuniform variation from normal to abnormal. This argues against using linear dimensional applications of these scales to assess individuals ranging from mild to severe in symptom severity. Separate scales may be necessary to characterize lower and higher ranges of clinical severity. [ABSTRACT FROM AUTHOR]

Referrals for gender dysphoria (GD), characterized by a distressful incongruence between gender identity and at-birth assigned sex, are steadily increasing. The underlying neurobiology, and the mechanisms of the often-beneficial cross-sex hormone treatment are unknown. Here, we test hypothesis that own body perception networks (incorporated in the default mode network—DMN, and partly in the salience network—SN), are different in trans-compared with cis-gender persons. We also investigate whether these networks change with cross-sex hormone treatment. Forty transmen (TrM) and 25 transwomen (TrW) were scanned before and after cross-sex hormone institution. We used our own developed Body Morph test (BM), to assess the perception of own body as self. Fifteen cisgender persons were controls. Within and between-group differences in functional connectivity were calculated using independent components analysis within the DMN, SN, and motor network (a control network). Pretreatment, TrM and TrW scored lower "self" on the BM test than controls. Their functional connections were weaker in the anterior cingulate-, mesial prefrontal-cortex (mPFC), precuneus, the left angular gyrus, and superior parietal cortex of the DMN, and ACC in the SN "Self" identification and connectivity in the mPFC in both TrM and TrW increased from scan 1 to 2, and at scan 2 no group differences remained. The neurobiological underpinnings of GD seem subserved by cerebral structures composing major parts of the DMN. [ABSTRACT FROM AUTHOR]

Recent task fMRI studies suggest that individual differences in trait empathy and empathic concern are mediated by patterns of connectivity between self-other resonance and top-down control networks that are stable across task demands. An untested implication of this hypothesis is that these stable patterns of connectivity should be visible even in the absence of empathy tasks. Using machine learning, we demonstrate that patterns of resting state fMRI connectivity (i.e. the degree of synchronous BOLD activity across multiple cortical areas in the absence of explicit task demands) of resonance and control networks predict trait empathic concern (n = 58). Empathic concern was also predicted by connectivity patterns within the somatomotor network. These findings further support the role of resonance-control network interactions and of somatomotor function in our vicariously driven concern for others. Furthermore, a practical implication of these results is that it is possible to assess empathic predispositions in individuals without needing to perform conventional empathy assessments. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are potentially life-threatening conditions whose partially overlapping phenomenology—distorted perception of appearance, obsessions/compulsions, and limited insight—can make diagnostic distinction difficult in some cases. Accurate diagnosis is crucial, as the effective treatments for AN and BDD differ. To improve diagnostic accuracy and clarify the contributions of each of the multiple underlying factors, we developed a two-stage machine learning model that uses multimodal, neurobiology-based, and symptom-based quantitative data as features: task-based functional magnetic resonance imaging data using body visual stimuli, graph theory metrics of white matter connectivity from diffusor tensor imaging, and anxiety, depression, and insight psychometric scores. In a sample of unmedicated adults with BDD (n = 29), unmedicated adults with weight-restored AN (n = 24), and healthy controls (n = 31), the resulting model labeled individuals with an accuracy of 76%, significantly better than the chance accuracy of 35% (). In the multivariate model, reduced white matter global efficiency and better insight were associated more with AN than with BDD. These results improve our understanding of the relative contributions of the neurobiological characteristics and symptoms of these disorders. Moreover, this approach has the potential to aid clinicians in diagnosis, thereby leading to more tailored therapy. [ABSTRACT FROM AUTHOR]

Own body perception, and differentiating and comparing one's body to another person's body, are common cognitive functions that have relevance for self‐identity and social interactions. In several psychiatric conditions, including anorexia nervosa, body dysmorphic disorder, gender dysphoria, and autism spectrum disorder, self and own body perception, as well as aspects of social communication are disturbed. Despite most of these conditions having skewed prevalence sex ratios, little is known about whether the neural basis of own body perception differs between the sexes. We addressed this question by investigating brain activation using functional magnetic resonance imaging during a Body Perception task in 15 male and 15 female healthy participants. Participants viewed their own body, bodies of same‐sex, or opposite‐sex other people, and rated the degree that they appeared like themselves. We found that men and women did not differ in the pattern of brain activation during own body perception compared to a scrambled control image. However, when viewing images of other bodies of same‐sex or opposite‐sex, men showed significantly stronger activations in attention‐related and reward‐related brain regions, whereas women engaged stronger activations in striatal, medial‐prefrontal, and insular cortices, when viewing the own body compared to other images of the opposite sex. It is possible that other body images, particularly of the opposite sex, may be of greater salience for men, whereas images of own bodies may be more salient for women. These observations provide tentative neurobiological correlates to why women may be more vulnerable than men to conditions involving own body perception. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) share distorted perceptions of appearance with extreme negative emotion, yet the neural phenotypes of emotion processing remain underexplored in them, and they have never been directly compared. We sought to determine if shared and disorder-specific fronto-limbic connectivity patterns characterize these disorders. FMRI data was obtained from three unmedicated groups: BDD (n = 32), weight-restored AN (n = 25), and healthy controls (HC; n = 37), while they viewed fearful faces and rated their own degree of fearfulness in response. We performed dynamic effective connectivity modeling with medial prefrontal cortex (mPFC), rostral anterior cingulate cortex (rACC), and amygdala as regions-of-interest (ROI), and assessed associations between connectivity and clinical variables. HCs exhibited significant within-group bidirectional mPFC-amygdala connectivity, which increased across the blocks, whereas BDD participants exhibited only significant mPFC-to-amygdala connectivity (P < 0.05, family-wise error corrected). In contrast, participants with AN lacked significant prefrontal-amygdala connectivity in either direction. AN showed significantly weaker mPFC-to-amygdala connectivity compared to HCs (P = 0.0015) and BDD (P = 0.0050). The mPFC-to-amygdala connectivity was associated with greater subjective fear ratings (R2 = 0.11, P = 0.0016), eating disorder symptoms (R2 = 0.33, P = 0.0029), and anxiety (R2 = 0.29, P = 0.0055) intensity scores. Our findings, which suggest a complex nosological relationship, have implications for understanding emotion regulation circuitry in these related psychiatric disorders, and may have relevance for current and novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective:Obsessive-compulsive disorder (OCD) is associated with impaired functioning and depression. Our aim was to examine relationships between OCD symptoms, depression and functioning before and after exposure and response prevention (ERP), a type of cognitive-behavioural therapy for OCD, specifically examining whether functioning, depression and other cognitive factors like rumination and worry acted as mediators. Methods:Forty-four individuals with OCD were randomised to 4 weeks of intensive ERP treatment first (n = 23) or waitlist then treatment (n = 21). We used a bootstrapping method to examine mediation models. Results:OCD symptoms, depression and functioning significantly improved from pre- to post-intervention. Functioning mediated the relationship between OCD symptoms and depression and the relationship between functioning and depression was stronger at post-treatment. Depression mediated the relationship between OCD symptoms and functioning, but only at post-intervention. Similarly, rumination mediated the relationship between OCD symptoms and depression at post-intervention. Conclusions:Our findings suggest that after ERP, relationships between depression and functioning become stronger. Following ERP, treatment that focuses on depression and functioning, including medication management for depression, cognitive approaches targeting rumination, and behavioural activation to boost functionality may be important clinical interventions for OCD patients. [ABSTRACT FROM PUBLISHER]

Cognitive behavioral therapy (CBT) is an effective treatment for many with obsessive-compulsive disorder (OCD). However, response varies considerably among individuals. Attaining a means to predict an individual's potential response would permit clinicians to more prudently allocate resources for this often stressful and time-consuming treatment. We collected resting-state functional magnetic resonance imaging from adults with OCD before and after 4 weeks of intensive daily CBT. We leveraged machine learning with cross-validation to assess the power of functional connectivity (FC) patterns to predict individual posttreatment OCD symptom severity. Pretreatment FC patterns within the default mode network and visual network significantly predicted posttreatment OCD severity, explaining up to 67% of the variance. These networks were stronger predictors than pretreatment clinical scores. Results have clinical implications for developing personalized medicine approaches to identifying individual OCD patients who will maximally benefit from intensive CBT. [ABSTRACT FROM AUTHOR]

Gender dysphoria (GD) is characterized by incongruence between one's identity and gender assigned at birth. The biological mechanisms of GD are unclear. We investigated brain network connectivity patterns involved in own body perception in the context of self in GD. Twenty-seven female-to-male (FtM) individuals with GD, 27 male controls, and 27 female controls underwent resting state fMRI. We compared functional connections within intrinsic connectivity networks involved in self-referential processes and own body perception -default mode network (DMN) and salience network - and visual networks, using independent components analyses. Behavioral correlates of network connectivity were also tested using self-perception ratings while viewing own body images morphed to their sex assigned at birth, and to the sex of their gender identity. FtM exhibited decreased connectivity of anterior and posterior cingulate and precuneus within the DMN compared with controls. In FtM, higher "self" ratings for bodies morphed towards the sex of their gender identity were associated with greater connectivity of the anterior cingulate within the DMN, during long viewing times. In controls, higher ratings for bodies morphed towards their gender assigned at birth were associated with right insula connectivity within the salience network, during short viewing times. Within visual networks FtM showed weaker connectivity in occipital and temporal regions. Results suggest disconnectivity within networks involved in own body perception in the context of self in GD. Moreover, perception of bodies in relation to self may be reflective rather than reflexive, as a function of mesial prefrontal processes. These may represent neurobiological correlates to the subjective disconnection between perception of body and self-identification. [ABSTRACT FROM AUTHOR]

Background: Relapse after treatment for anorexia nervosa (AN) is a significant clinical problem. Given the level of chronicity, morbidity, and mortality experienced by this population, it is imperative to understand the driving forces behind apparently high relapse rates. However, there is a lack of consensus in the field on an operational definition of relapse, which hinders precise and reliable estimates of the severity of this issue. The primary goal of this paper was to review prior studies of AN addressing definitions of relapse, as well as relapse rates. Methods: Data sources included PubMed and PsychINFO through March 19th, 2016. A systematic review was performed following the PRISMA guidelines. A total of (N = 27) peer-reviewed English language studies addressing relapse, remission, and recovery in AN were included. Results: Definitions of relapse in AN as well as definitions of remission or recovery, on which relapse is predicated, varied substantially in the literature. Reported relapse rates ranged between 9 and 52%, and tended to increase with increasing duration of follow-up. There was consensus that risk for relapse in persons with AN is especially high within the first year following treatment. Discussion: Standardized definitions of relapse, as well as remission and recovery, are needed in AN to accelerate clinical and research progress. This should improve the ability of future longitudinal studies to identify clinical, demographic, and biological characteristics in AN that predict relapse versus resilience, and to comparatively evaluate relapse prevention strategies. We propose standardized criteria for relapse, remission, and recovery, for further consideration. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Individuals with anorexia nervosa (AN) and body dysmorphic disorder (BDD) exhibit distorted perception and negative evaluations of their own appearance; however, little is known about how they perceive others' appearance, and whether or not the conditions share perceptual distortions. Method Thirty participants with BDD, 22 with AN, now weight-restored, and 39 healthy comparison participants (HC) rated photographs of others' faces and bodies on attractiveness, how overweight or underweight they were, and how much photographs triggered thoughts of their own appearance. We compared responses among groups by stimulus type and by level-of-detail (spatial frequency). Results Compared to HCs, AN and BDD had lower attractiveness ratings for others' bodies and faces for high-detail and low-detail images, rated bodies as more overweight, and were more triggered to think of their own appearance for faces and bodies. In AN, symptom severity was associated with greater triggering of thoughts of own appearance and higher endorsement of overweight ratings for bodies. In BDD, symptom severity was associated with greater triggering of thoughts of own appearance for bodies and higher overweight ratings for low-detail images. BDD was more triggered to think of own facial appearance than AN. Discussion AN and BDD show similar behavioral phenotypes of negative appearance evaluations for others' faces and bodies, and have thoughts of their own appearance triggered even for images outside of their primary appearance concerns, suggesting a more complex cross-disorder body-image phenotype than previously assumed. Future treatment strategies may benefit from addressing how these individuals evaluate others in addition to themselves. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:127-138) [ABSTRACT FROM AUTHOR]

Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the highest dose. These reports were accompanied by increased BOLD and ASL activation of the right insular cortex at the highest dose. Different responses across insula subregions were also observed. During anticipation, insula activation increased in more anterior regions. During stimulation, activation increased in the mid-dorsal and posterior insula on the right, but decreased in the same regions on the left. This study demonstrates the feasibility of phMRI for assessing brain activation during adrenergic interoceptive stimulation, and provides further evidence supporting a dynamic role for the insula in representing changes in cardiorespiratory states. This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Several case reports of Wernicke's Encephalopathy in anorexia nervosa (AN) caused by thiamine deficiency have described mammillary body (MB) injury, but systematic studies are lacking. Here we evaluated whether underweight and weight-restored individuals with AN demonstrate evidence of abnormal MB morphology, via retrospective examination of a previously collected data set. Method Using standard-resolution T1-weighted magnetic resonance imaging at 3 Tesla, we measured MB volume and fornix area in a cross-sectional study of 12 underweight AN, 20 weight-restored AN, and 30 age- and sex-matched healthy comparisons. Because of the small size of these structures, a manual tracing approach was necessary to obtain accurate measurements. A blinded expert rater manually traced MB and fornix structures in each participant. Results We observed significantly smaller MB volumes in the underweight AN group. However, the weight-restored AN group exhibited significantly larger MB volumes. The right fornix was smaller in the weight-restored AN group only. Discussion These findings suggest the possibility that MB volume and fornix area could represent potential biomarkers of acute weight loss and restoration, respectively. Verification of this finding through prospective studies evaluating MB morphology, cognition, and thiamine levels longitudinally across individual illness trajectories might be warranted. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:920-929) [ABSTRACT FROM AUTHOR]

Transsexualism is characterized by feelings of incongruity between one's natal sex and one's gender identity. It is unclear whether transsexual individuals have a body image that is more congruent with their gender identity than their sex assigned at birth (natal sex) and, if so, whether there are contributions from perceptual dysfunctions. We compared 16 pre-hormone treatment female-to-male transsexual (FtM) individuals to 20 heterosexual female and 20 heterosexual male controls on a visual identification task. Participants viewed photographs of their own body that were morphed by different degrees to bodies of other females or males, and were instructed to rate "To what degree is this picture you?" We also tested global vs. local visual processing using the inverted faces task. FtM differed from both control groups in demonstrating higher self-identification ratings for bodies morphed to the sex congruent with their gender identity, and across a broad range of morph percentages. This difference was more pronounced for longer viewing durations. FtM showed reduced accuracy for upright faces compared with female controls for short duration stimuli, but no advantage for inverted faces. These results suggest different own body identification in FtM, consisting of a relatively diffuse identification with body images congruent with their gender identity. This is more likely accounted for by conscious, cognitive factors than perceptual differences. [ABSTRACT FROM AUTHOR]

We previously demonstrated that carbon dioxide inhalation could induce panic anxiety in a group of rare lesion patients with focal bilateral amygdala damage. To further elucidate the amygdala-independent mechanisms leading to aversive emotional experiences, we retested two of these patients (B.G. and A.M.) to examine whether triggering palpitations and dyspnea via stimulation of nonchemosensory interoceptive channels would be sufficient to elicit panic anxiety. Participants rated their affective and sensory experiences following bolus infusions of either isoproterenol, a rapidly acting peripheral β-adrenergic agonist akin to adrenaline, or saline. Infusions were administered during two separate conditions: a panic induction and an assessment of cardiorespiratory interoception. Isoproterenol infusions induced anxiety in both patients, and full-blown panic in one (patient B.G.). Although both patients demonstrated signs of diminished awareness for cardiac sensation, patient A.M., who did not panic, reported a complete lack of awareness for dyspnea, suggestive of impaired respiratory interoception. These findings indicate that the amygdala may play a role in dynamically detecting changes in cardiorespiratory sensation. The induction of panic anxiety provides further evidence that the amygdala is not required for the conscious experience of fear induced via interoceptive sensory channels. [ABSTRACT FROM AUTHOR]

ABSTRACT 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. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:889-897) [ABSTRACT FROM AUTHOR]

This article presents a novel approach for understanding information exchange efficiency and its decay across hierarchies of modularity, from local to global, of the structural human brain connectome. Magnetic resonance imaging techniques have allowed us to study the human brain connectivity as a graph, which can then be analyzed using a graph-theoretical approach. Collectively termed brain connectomics, these sophisticated mathematical techniques have revealed that the brain connectome, like many networks, is highly modular and brain regions can thus be organized into communities or modules. Here, using tractography-informed structural connectomes from 46 normal healthy human subjects, we constructed the hierarchical modularity of the structural connectome using bifurcating dendrograms. Moving from fine to coarse (i.e., local to global) up the connectome's hierarchy, we computed the rate of decay of a new metric that hierarchically preferentially weighs the information exchange between two nodes in the same module. By computing 'embeddedness'-the ratio between nodal efficiency and this decay rate, one could thus probe the relative scale-invariant information exchange efficiency of the human brain. Results suggest that regions that exhibit high embeddedness are those that comprise the limbic system, the default mode network, and the subcortical nuclei. This supports the presence of near-decomposability overall yet relative embeddedness in select areas of the brain. The areas we identified as highly embedded are varied in function but are arguably linked in the evolutionary role they play in memory, emotion and behavior. Hum Brain Mapp 36:3653-3665, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Intensive cognitive-behavioral therapy (CBT) can effectively reduce symptoms in obsessive--compulsive disorder (OCD). However, many relapse after treatment. Few studies have investigated biological markers predictive of follow-up clinical status. The objective was to determine if brain network connectivity patterns prior to intensive CBT predict worsening of clinical symptoms during follow-up. Methods: We acquired resting-state functional magnetic resonance imaging data from 17 adults with OCD prior to and following 4 weeks of intensive CBT. Functional connectivity data were analyzed to yield graph-theory metrics. We examined the relationship between pre-treatment connectome properties and OCD clinical symptoms before and after treatment and during a 12-month follow-up period. Results: Mean OCD symptom decrease was 40.4±16.4% pre- to post-treatment (64.7% responded; 58.8% remitted), but 35.3% experienced clinically significant worsening during follow-up. From pre- to post-treatment, small-worldness and clustering coefficient significantly increased. Decreases in modularity correlated with decreases in OCD symptoms. Higher pre-treatment small-world connectivity was significantly associated with worsening of OCD symptoms during the follow-up period. Psychometric and neurocognitive measures pre- and post-treatment were not significant predictors. Conclusion: This is the first graph-theory connectivity study of the effects of CBT in OCD, and the first to test associations with follow-up clinical status. Results show functional network efficiency as a biomarker of CBT response and relapse in OCD. CBT increases network efficiency as it alleviates symptoms in most patients, but those entering therapy with already high network efficiency are at greater risk of relapse. Results have potential clinical implications for treatment selection. [ABSTRACT FROM AUTHOR]

In this article, we present path length associated community estimation (PLACE), a comprehensive framework for studying node-level community structure. Instead of the well-known Q modularity metric, PLACE utilizes a novel metric, ΨPL, which measures the difference between intercommunity versus intracommunity path lengths. We compared community structures in human healthy brain networks generated using these two metrics and argued that ΨPL may have theoretical advantages. PLACE consists of the following: (1) extracting community structure using top-down hierarchical binary trees, where a branch at each bifurcation denotes a collection of nodes that form a community at that level, (2) constructing and assessing mean group community structure, and (3) detecting node-level changes in community between groups. We applied PLACE and investigated the structural brain networks obtained from a sample of 25 euthymic bipolar I subjects versus 25 gender- and age-matched healthy controls. Results showed community structural differences in posterior default mode network regions, with the bipolar group exhibiting left-right decoupling. Hum Brain Mapp 35:2253-2264, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses research on the causes of body dysmorphic disorder (BDD) and the proposed BDD model. Several BDD developmental factors include physical, emotional and sexual abuse, teasing related to acne and cultural influences. The researchers examined neurocognitive functioning in BDD that may give information on the etiology and maintenance of the symptoms of BDD such as being overfocused on details when given a complex visuospatial task. Also noted are neurobiological factors in BDD including brain morphometry, genetics and neurochemistry.

The published literature on olfactory reference syndrome (ORS) spans more than a century and provides consistent descriptions of its clinical features. The core symptom is preoccupation with the belief that one emits a foul or offensive body odor, which is not perceived by others. This syndrome is associated with substantial distress and disability. DSM-IV and ICD-10 do not explicitly mention ORS, but note convictions about emitting a foul body odor in their description of delusional disorder, somatic type. However, the fact that such symptoms can be nondelusional poses a diagnostic conundrum. Indeed, DSM-IV also mentions fears about the offensiveness of one's body odor in the social phobia text (as a symptom of taijin kyofusho). There also seems to be phenomenological overlap with body dysmorphic disorder, obsessive–compulsive disorder, and hypochondriasis. This article provides a focused review of the literature to address issues for DSM-V, including whether ORS should continue to be mentioned as an example of another disorder or should be included as a separate diagnosis. We present a number of options and preliminary recommendations for consideration for DSM-V. Because research is still very limited, it is unclear how ORS should best be classified. Nonetheless, classifying ORS as a type of delusional disorder seems problematic. Given this syndrome's consistent clinical description across cultures for more than a century, substantial morbidity and a small but growing research literature, we make the preliminary recommendation that ORS be included in DSM-Vs Appendix of Criteria Sets Provided for Further Study, and we suggest diagnostic criteria. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A conference paper about the presence of abnormal brain activation patterns in patients with body dysmorphic disorder (BDD) is presented. It discusses BDD and how affected individuals are preoccupied with perceived defects in appearance. It compares BDD patients and normal control patients and how they react towards visual face stimuli and reveals visual processing and frontostrital system abnormalities in BDD individuals.

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. [ABSTRACT FROM AUTHOR]