The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

White matter microstructure in habit and reward circuits in anorexia nervosa: Insights from a neurite orientation dispersion and density imaging study.

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.

Amygdala subfield and prefrontal cortex abnormalities in patients with functional seizures.

BACKGROUND: Functional seizures (FS) are paroxysmal episodes, resembling epileptic seizures, but without underlying epileptic abnormality. The aetiology and neuroanatomic associations are incompletely understood. Recent brain imaging data indicate cerebral changes, however, without clarifying possible pathophysiology. In the present study, we specifically investigated the neuroanatomic changes in subregions of the amygdala and hippocampus in FS. METHODS: T1 MRI scans of 37 female patients with FS and 37 age-matched female seizure naïve controls (SNC) were analyzed retrospectively in FreeSurfer version 7.1. Seizure naïve controls included patients with depression and anxiety disorders. The analysis included whole-brain cortical thickness, subcortical volumes, and subfields of the amygdala and hippocampus. Group comparisons were carried out using multivariable linear models. RESULTS: The FS and SNC groups did not differ in the whole hippocampus and amygdala volumes. However, patients had a significant reduction of the right lateral amygdala volume (p = 0.00041), an increase of the right central amygdala, (p = 0.037), and thinning of the left superior frontal gyrus (p = 0.024). Additional findings in patients were increased volumes of the right medial amygdala (p = 0.031), left anterior amygdala (p = 0.017), and left dentate gyrus of the hippocampus (p = 0.035). CONCLUSIONS: The observations from the amygdala and hippocampus segmentation affirm that there are neuroanatomic associations of FS. The pattern of these changes aligned with some of the cerebral changes described in chronic stress conditions and depression. The pattern of detected changes further study, and may, after validation, provide biomarkers for diagnosis and treatment.

Clinical MRI morphological analysis of functional seizures compared to seizure-naïve and psychiatric controls.

PURPOSE: Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS and clinically relevant comparison populations. METHODS: Quality-screened clinical-grade MRIs were acquired from 666 patients from 2006 to 2020. Morphometric features were quantified with FreeSurfer v6. Mixed-effects linear regression compared the volume, thickness, and surface area within 201 regions-of-interest for 90 patients with FS, compared to seizure-naïve patients with depression (n = 243), anxiety (n = 68), and obsessive-compulsive disorder (OCD, n = 41), respectively, and to other seizure-naïve controls with similar quality MRIs, accounting for the influence of multiple confounds including depression and anxiety based on chart review. These comparison populations were obtained through review of clinical records plus research studies obtained on similar scanners. RESULTS: After Bonferroni-Holm correction, patients with FS compared with seizure-naïve controls exhibited thinner bilateral superior temporal cortex (left 0.053 mm, p = 0.014; right 0.071 mm, p = 0.00006), thicker left lateral occipital cortex (0.052 mm, p = 0.0035), and greater left cerebellar white-matter volume (1085 mm3, p = 0.0065). These findings were not accounted for by lower MRI quality in patients with FS. CONCLUSIONS: These results reinforce prior indications of structural neuroimaging correlates of FS and, in particular, distinguish brain morphology in FS from that in depression, anxiety, and OCD. Future work may entail comparisons with other psychiatric disorders including bipolar and schizophrenia, as well as exploration of brain structural heterogeneity within FS.

Cortical Gyrification in Transgender Individuals.

Gender incongruence (GI) is characterized by a feeling of estrangement from the own body in the context of self. GI is often described in people who identify as transgender. The underlying mechanisms are unknown. Data from MRI measurements and tests of own body perception triggered us to pose a model that GI in transgender persons (TGI) could be associated with a disconnection within the brain circuits mediating the perception of own body as self. This is a departure from a previous model of sex atypical cerebral dimorphism, introducing a concept that better accords with a core feature of TGI. The present MRI study of 54 hormone naive transmen (TrM), 38 transwomen (TrW), 44 cismen and 41 ciswomen show that cortical gyrification, a metric that reflects early maturation of cerebral cortex, is significantly lower in transgender compared with cisgender participants. This reduction is limited to the occipito-parietal cortex and the sensory motor cortex, regions encoding own body image and body ownership. Moreover, the cortical gyrification correlated inversely with own body-self incongruence in these regions. These novel data suggest that GI in TGI may originate in the neurodevelopment of body image encoding regions. The results add potentially to understanding neurobiological contributors to gender identity.

Online Video Teletherapy Treatment of Obsessive-Compulsive Disorder Using Exposure and Response Prevention: Clinical Outcomes From a Retrospective Longitudinal Observational Study.

BACKGROUND: Exposure and response prevention, a type of cognitive-behavioral therapy, is an effective first-line treatment for obsessive-compulsive disorder (OCD). Despite extensive evidence of the efficacy of exposure and response prevention (ERP) from clinical studies and in real-world samples, it is still underused as a treatment. This is likely due to the limits to access to care that include the availability of adequately trained therapists, as well as geographical location, time, and cost barriers. To address these, NOCD created a digital behavioral health treatment for OCD using ERP delivered via video teletherapy and with technology-assisted elements including app-based therapy tools and between-session therapist messaging. OBJECTIVE: We examined treatment outcomes in a large naturalistic sample of 3552 adults with a primary OCD diagnosis who received NOCD treatment. METHODS: The treatment model consisted of twice-weekly, live, face-to-face video teletherapy ERP for 3 weeks, followed by 6 weeks of once-weekly brief video teletherapy check-ins for 30 minutes. Assessments were conducted at baseline, at midpoint after completion of 3 weeks of twice-weekly sessions, and at the end of 6 weeks of brief check-ins (endpoint). Longitudinal assessments were also obtained at 3, 6, 9, and 12 months after endpoint. RESULTS: Treatment resulted in clinically and statistically significant improvements, with a 43.4% mean reduction in obsessive-compulsive symptoms (g=1.0; 95% CI 0.93 to 1.03) and a 62.9% response rate. Treatment also resulted in a 44.2% mean reduction in depression, a 47.8% mean reduction in anxiety, and a 37.3% mean reduction in stress symptoms. Quality of life improved by a mean of 22.7%. Reduction in OCD symptoms and response rates were similar for those with mild, moderate, or severe symptoms. The mean duration of treatment was 11.5 (SD 4.0) weeks, and the mean total therapist time was 10.6 (SD 1.1) hours. Improvements were maintained at 3, 6, 9, and 12 months. CONCLUSIONS: In this sample, representing the largest reported treated cohort of patients with OCD to date, video teletherapy treatment demonstrated effectiveness in reducing obsessive-compulsive and comorbid symptoms and improved quality of life. Further, it achieved meaningful results in less than half the total therapist time compared with standard once-weekly outpatient treatment, an efficiency that represents substantial monetary and time savings. The effect size was large and similar to studies of in-person ERP. This technology-assisted remote treatment is readily accessible for patients, offering an advancement in the field in the dissemination of effective evidence-based care for OCD.

Neurosurgery and neuromodulation for anorexia nervosa in the 21st century: a systematic review of treatment outcomes.

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.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

Reliability of additional reported seizure manifestations to identify dissociative seizures.

PURPOSE: Descriptions of seizure manifestations (SM), or semiology, can help localize the symptomatogenic zone and subsequently included brain regions involved in epileptic seizures, as well as identify patients with dissociative seizures (DS). Patients and witnesses are not trained observers, so these descriptions may vary from expert review of seizure video recordings of seizures. To better understand how reported factors can help identify patients with DS or epileptic seizures (ES), we evaluated the associations between more than 30 SMs and diagnosis using standardized interviews. METHODS: Based on patient- and observer-reported data from 490 patients with diagnoses documented by video-electoencephalography, we compared the rate of each SM in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic seizure-like events (PSLE), mixed DS and ES, and inconclusive testing. RESULTS: In addition to SMs that we described in a prior manuscript, the following were associated with DS: light triggers, emotional stress trigger, pre-ictal and post-ictal headache, post-ictal muscle soreness, and ictal sensory symptoms. The following were associated with ES: triggered by missing medication, aura of déjà vu, and leftward eye deviation. There were numerous manifestations separately associated with mixed ES and DS. CONCLUSIONS: Reported SM can help identify patients with DS, but no manifestation is pathognomonic for either ES or DS. Patients with mixed ES and DS reported factors divergent from both ES-alone and DS-alone.

Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex.

Gender identity is a core aspect of self-identity and is usually congruent with birth-assigned sex and own body sex-perception. The neuronal circuits underlying gender identity are unknown, but greater awareness of transgenderism has sparked interest in studying these circuits. We did this by comparing brain activation and connectivity in transgender individuals (for whom gender identity and birth-assigned sex are incongruent) with that in cisgender controls (for whom they are congruent) when performing a body self-identification task during functional magnetic resonance imaging. Thirty transgender and 30 cisgender participants viewed images of their own bodies and bodies morphed in sex toward or opposite to birth-assigned sex, rating each image to the degree they identified with it. While controls identified with images of themselves, transgender individuals identified with images morphed "opposite" to their birth-assigned sex. After covarying out the effect of self-similarity ratings, both groups activated similar self- and body-processing systems when viewing bodies that aligned with their gender identity rather than birth-assigned sex. Additionally, transgender participants had greater limbic involvement when viewing ambiguous, androgynous images of themselves morphed toward their gender identity. These results shed light on underlying self-processing networks specific to gender identity and uncover additional involvement of emotional processing in transgender individuals.

Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder.

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.

Semantic Linkages of Obsessions From an International Obsessive-Compulsive Disorder Mobile App Data Set: Big Data Analytics Study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts, urges, or images (obsessions) and repetitive physical or mental behaviors (compulsions). Previous factor analytic and clustering studies suggest the presence of three or four subtypes of OCD symptoms. However, these studies have relied on predefined symptom checklists, which are limited in breadth and may be biased toward researchers' previous conceptualizations of OCD. OBJECTIVE: In this study, we examine a large data set of freely reported obsession symptoms obtained from an OCD mobile app as an alternative to uncovering potential OCD subtypes. From this, we examine data-driven clusters of obsessions based on their latent semantic relationships in the English language using word embeddings. METHODS: We extracted free-text entry words describing obsessions in a large sample of users of a mobile app, NOCD. Semantic vector space modeling was applied using the Global Vectors for Word Representation algorithm. A domain-specific extension, Mittens, was also applied to enhance the corpus with OCD-specific words. The resulting representations provided linear substructures of the word vector in a 100-dimensional space. We applied principal component analysis to the 100-dimensional vector representation of the most frequent words, followed by k-means clustering to obtain clusters of related words. RESULTS: We obtained 7001 unique words representing obsessions from 25,369 individuals. Heuristics for determining the optimal number of clusters pointed to a three-cluster solution for grouping subtypes of OCD. The first had themes relating to relationship and just-right; the second had themes relating to doubt and checking; and the third had themes relating to contamination, somatic, physical harm, and sexual harm. All three clusters showed close semantic relationships with each other in the central area of convergence, with themes relating to harm. An equal-sized split-sample analysis across individuals and a split-sample analysis over time both showed overall stable cluster solutions. Words in the third cluster were the most frequently occurring words, followed by words in the first cluster. CONCLUSIONS: The clustering of naturally acquired obsessional words resulted in three major groupings of semantic themes, which partially overlapped with predefined checklists from previous studies. Furthermore, the closeness of the overall embedded relationships across clusters and their central convergence on harm suggests that, at least at the level of self-reported obsessional thoughts, most obsessions have close semantic relationships. Harm to self or others may be an underlying organizing theme across many obsessions. Notably, relationship-themed words, not previously included in factor-analytic studies, clustered with just-right words. These novel insights have potential implications for understanding how an apparent multitude of obsessional symptoms are connected by underlying themes. This observation could aid exposure-based treatment approaches and could be used as a conceptual framework for future research.

Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a "scar" due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects. METHODS: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters. DISCUSSION: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and "scar" effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.

Sex differences in own and other body perception.

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.

Testosterone Effects on the Brain in Transgender Men.

Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas.

Relationships between obsessive-compulsive disorder, depression and functioning before and after exposure and response prevention therapy.

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.

Panic Anxiety in Humans with Bilateral Amygdala Lesions: Pharmacological Induction via Cardiorespiratory Interoceptive Pathways.

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 non-chemosensory 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 ß-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. SIGNIFICANCE STATEMENT: We found that monozygotic twins with focal bilateral amygdala lesions report panic anxiety in response to intravenous infusions of isoproterenol, a ß-adrenergic agonist similar to adrenaline. Heightened anxiety was evident in both twins, with one twin experiencing a panic attack. The twin who did not panic displayed signs of impaired cardiorespiratory interoception, including a complete absence of dyspnea sensation. These findings highlight that the amygdala is not strictly required for the experience of panic anxiety, and suggest that neural systems beyond the amygdala are also involved. Determining these additional systems could provide key neural modulation targets for future anxiolytic treatments.

Appearance evaluation of others' faces and bodies in anorexia nervosa and body dysmorphic disorder.

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).

Mammillary body volume abnormalities in anorexia nervosa.

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).