Transdiagnostic modeling of clinician-rated symptoms in affective and nonaffective psychotic disorders.

Prevailing factor models of psychosis are centered on schizophrenia-related disorders defined by the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases, restricting generalizability to other clinical presentations featuring psychosis, even though affective psychoses are more common. This study aims to bridge this gap by conducting exploratory and confirmatory factor analyses, utilizing clinical ratings collected from patients with either affective or nonaffective psychoses (n = 1,042). Drawing from established clinical instruments, such as the Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Montgomery-Åsberg Depression Rating Scale, a broad spectrum of core psychotic symptoms was considered for the model development. Among the candidate models considered, including correlated factors and multifactor models, a model with seven correlated factors encompassing positive symptoms, negative symptoms, depression, mania, disorganization, hostility, and anxiety was most interpretable with acceptable fit. The seven factors exhibited expected associations with external validators, were replicable through cross-validation, and were generalizable across affective and nonaffective psychoses. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genetic Testing History in Adults with Autism Spectrum Disorder.

Background & Objectives: Many genes have been identified in autism spectrum disorder (ASD). Yet little is known about how many adults with ASD receive recommended genetic testing and their outcomes. We investigated the percentage of adults with ASD who received genetic testing using recommended methods in our ASD specialty clinic and the percentage with positive findings. Methods: Potentially eligible adults were identified through search of our health system data repository and ASD diagnoses confirmed using review of relevant medical records by consensus of psychiatrists specializing in ASD. Patients were included (N=630) who had at least one visit with a qualifying clinician between 5/1/2010 and 12/15/2020 and demographic data available. Data were collected through manual retrospective review of the electronic health record. Results: Only 41% of the adults with ASD (261/630) had a history of genetic testing documented in the medical record. Genetic testing was declined by patients or families for 11% (72) of records and not recorded in 47% (297). Mean (SD; range) age for the 261 adults with testing documented was 28.5 (5.3; 22-58) years. Sixty-seven (26%) were identified as female, 14 (6%) as Asian, 8 (3%) as Black or African American, 226 (89%) as White, 6 (2%) as other race, and 2 (1%) as Hispanic. 189 (73%) had intellectual disability. Ninety-one percent (236) had the genetic testing method recorded. Only 54% (95% CI: 46%, 61%) of patients had testing using a recommended method (chromosomal array, autism/intellectual disability sequencing panel, or exome sequencing). Few adults had received testing with sequencing technologies. A genetic cause of ASD was found in 28% (95% CI: 19%, 39%) of the 121 adults with results from ASD-related genetic testing recorded. Conclusions: Genetic testing can offer clinical and research insights. Yet it is underutilized in this population of adults with ASD. Nearly half of the adults in our sample lacked documentation of genetic testing. Thus, the percentage of adults with confirmed ASD who had any recommended genetic testing may be even lower than reported. Adults with ASD may benefit from having their genetic testing history reviewed in the clinic and the latest genetic testing performed.

Using Restricted Interests in Cognitive Behavioral Therapy for Children With Autism Spectrum Disorder: Results From a Preliminary Randomized Controlled Trial.

Children with autism spectrum disorder (ASD) exhibit significant deficits in social communication and emotion regulation skills. While cognitive behavioral therapy (CBT) applications appear promising, trials to date have largely excluded social communication skill development and have not been designed to include a wider range of emotional challenges. To our knowledge, the present study is the first to pilot a uniquely modified CBT program targeting emotion regulation, including social communication training, and explicitly focusing on the child's areas of circumscribed interest in order to teach skills and promote generalization. Forty participants were randomly assigned to either the CBT group or a waitlist control (WLC) group, resulting in 20 school-aged children in each group. The treatment approach was determined to be feasible and acceptable, and therapy engagement and attendance were reasonably high. Caregivers expressed high satisfaction with the program, qualitatively citing gains in skills such as social problem-solving, emotion identification, and identifying and processing cognitive distortions. The primary outcome of postintervention changes was not significantly different between the groups (CBT vs. WLC). The mean Social Skills Improvement System score decreased by 0.44 points (95% confidence interval [CI]: -5.04, 4.15) in the CBT group and increased by 0.41 points (95% CI: -4.23, 5.04) in the WLC group, and the postintervention changes were not significantly different between the groups (difference: -0.85; 95% CI: -7.29, 5.60; p = .79). The estimated rate of emotional dysregulation episodes decreased by a factor of 0.94 (95% CI: 0.57, 1.56) in the CBT group and increased by a factor of 1.07 (95% CI: 0.51, 2.24) for WLC (p = .74). Among those who reported emotional dysregulation episodes, the mean duration decreased by 1.39 minutes (95% CI: -3.90, 6.67) less for CBT than waitlist (p = .60). Although satisfaction, acceptability, and emotional dysregulation outcome results from this preliminary CBT treatment for ASD are promising, sample size and measurement limitations will be important considerations to inform future trials.

Can Patients With Narcissistic Personality Disorder Change? A Case Series.

ABSTRACT: The study was set out to establish the potential for psychotherapy to effect improvements in patients with narcissistic personality disorder (NPD). Eight patients with NPD who improved in treatment were identified. Consensus clinician/investigator diagnostic scores from before and after the psychotherapies were retroactively established on the Diagnostic Interview for Narcissism (DIN) and the Diagnostic Statistic Manual for Psychiatric Disorders, 5th Edition (DSM-5) Personality Disorder Section II criteria. Psychosocial functioning (work or school, romantic relationships) before and after the psychotherapies was retroactively evaluated as well. At the completion of the therapies after 2.5 to 5 years, all patients had improved, no longer met DIN or DSM-5 criteria for NPD, and showed better psychosocial functioning. Symptomatic improvements were associated with large effect sizes. In conclusion, changes in NPD can occur in treatment after 2.5 to 5 years. Future research should identify patient characteristics, interventions, and common processes in such improved cases that could help with development of treatments.

Trauma-informed systems change training has transcultural, transcontinental transformative healing power: An analysis of leaders in the United States and Angola, Africa.

The Institute for Trauma-Informed Systems Change (ITISC) facilitated a 2-day, 12-hr trauma-informed workshop, delivered virtually, using the Training for Change curriculum. The workshop took place in Portuguese in September 2021 with a group of Angolan leaders (N = 51) and in May 2022, in English, with neonatal intensive care unit (NICU) workers from the United States (N = 73). Surveys were administered before (Time [T] 0) and after the workshop (T1) and consisted of demographic questions and the Survey for Trauma-Informed Systems Change (STISC), which assesses system-wide knowledge and attitudes about trauma-informed systems change and the intersection of culture, safety, and acceptance in the workplace. At T1, 18 (35.3%) participants in the Angolan leaders' group and 46 (63.0%) in the NICU group completed the surveys. Mean scores on the STISC Self-Assessed Knowledge and Attitudes subscale and STISC System-Wide Knowledge and Attitudes subscale increased significantly in both groups after the training. Effect sizes were large for self-assessed knowledge and attitudes, Angolan leaders: d = 1.11, NICU: d = 1.97, and small-to-medium for system-wide knowledge and attitudes, Angolan leaders: d = 0.52, NICU: d = 0.38. Limitations include the relatively small sample size and low participation rates for survey responses. Future research should examine the efficacy of the curriculum in larger samples that include individuals from diverse professions and additional countries. Together, the findings provide initial support that this training can be directly translated and implemented on a global scale.

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.

Introduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging.Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure.Results: Higher PACAP levels were associated with greater EC NDI (ß = 0.0099, q = 0.032) and lower EC ODI (ß = -0.0073, q = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures.Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD.

PACAP was associated with altered entorhinal cortex neurite density in PTSD.PACAP was not associated with altered neurite density in amygdala or hippocampus.PACAP may impact arousal-associated memory circuits.

Guanfacine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents with Down Syndrome: A Retrospective Chart Review.

Study Design: Retrospective case series. Objectives: The objective of this study was to provide naturalistic data on the use of guanfacine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in a clinically referred sample of youth with Down syndrome (DS). Methods: The medical records of children and adolescents with DS who received guanfacine for the treatment of ADHD from a multidisciplinary neurodevelopmental disorder clinic between September 1, 2011, and September 10, 2021, were reviewed. Demographic and clinical characteristics, guanfacine dose and treatment duration, and adverse effects were recorded. Clinical Global Impression Scale (CGI) scores for ADHD symptom severity (S) and improvement (I) were retrospectively assigned by a child and adolescent psychiatrist based on review of the clinic notes. Response to guanfacine was defined as completion of at least 12 weeks of treatment and a Clinical Global Impression Improvement subscale rating ≤2 (1 = "very much improved" or 2 = "much improved"). Results: Twenty-one patients were eligible for inclusion, of whom 17 (81%) completed at least 12 weeks of guanfacine. Ten of the 21 patients (48%; 95% confidence interval [CI]: 28%-68%) responded to treatment. The median time on guanfacine treatment covered by the clinic notes was 50.4 weeks, with a range of 0.3 weeks to 7.5 years. Thirteen patients (62%) remained on guanfacine at the time of their most recent clinic note. Nine patients had adverse events documented in their clinic notes (43%; 95% CI: 24%-63%), most commonly sleepiness (n = 7) and constipation (n = 2). Conclusion: About half of patients with DS responded to guanfacine for the treatment of ADHD and many tolerated long-term use. Study limitations primarily relate to the retrospective nature of the study and small sample size.

Buspirone for the treatment of anxiety in Williams syndrome: a retrospective chart review study.

BACKGROUND: Williams syndrome (WS) is a rare genetic disorder associated with a high prevalence of anxiety disorders. Evidence-based pharmacologic treatments for anxiety in WS are lacking. The purpose of this study is to provide naturalistic data on the use of buspirone for the treatment of anxiety in WS. RESEARCH DESIGN AND METHODS: Medical records of 24 individuals with Williams syndrome (ages 7-47 years) and anxiety who received treatment with buspirone were reviewed. Treatment response to buspirone was rated by assigning a retrospective Clinical Global Impression Improvement subscale (CGI-I) score. RESULTS: Twenty-three of 24 (96%) patients completed at least a 16-week treatment course with buspirone. Sixteen patients (67%; 95% CI 47%, 82%) were treatment responders (CGI-I ≤ 2). Only 1 (4%) patient discontinued buspirone due to a treatment-emergent side effect (nausea and vomiting). The most common side effect was nausea (13%). Twenty (84%) patients remained on buspirone at the time of their most recent follow-up visit. CONCLUSIONS: In this retrospective study, the majority of patients responded to a 16-week course of buspirone. Prospective studies are warranted to further assess the efficacy and tolerability of buspirone for anxiety in WS.

Gonadal hormones impart male-biased behavioral vulnerabilities to immune activation via microglial mitochondrial function.

There is a strong male bias in the prevalence of many neurodevelopmental disorders such as autism spectrum disorder. However, the mechanisms underlying this sex bias remain elusive. Infection during the perinatal period is associated with an increased risk of neurodevelopmental disorder development. Here, we used a mouse model of early-life immune activation that reliably induces deficits in social behaviors only in males. We demonstrate that male-biased alterations in social behavior are dependent upon microglial immune signaling and are coupled to alterations in mitochondrial morphology, gene expression, and function specifically within microglia, the innate immune cells of the brain. Additionally, we show that this behavioral and microglial mitochondrial vulnerability to early-life immune activation is programmed by the male-typical perinatal gonadal hormone surge. These findings demonstrate that social behavior in males over the lifespan are regulated by microglia-specific mechanisms that are shaped by events that occur in early development.

Training for Lasting Change: Trauma-Informed Training Results in Improved and Sustained Individual and Organizational Knowledge, Attitudes, and Policies.

Objective: Trauma-informed care (TIC) trainings seek to improve individual and organizational recognition and care to individuals who have experienced trauma. However, whether TIC trainings result in long-term changes to an organization's policies and practices remains unclear. This article describes the effectiveness of a workshop designed to train professionals across disciplines in understanding and implementing TIC in their work and workplace.Methods: Between July 2021 and May 2022, participants completed a 2-day (approximately 12 hours) training in TIC that included didactics on cultural responsivity, the biological effects of trauma, the components of TIC, and how to deploy TIC within their organization. Prior to the training, participants completed a previously validated survey, the Survey for Trauma-Informed Systems Change, which evaluated their pre-training (T0) competency in TIC and the level of TIC within their organization. Within 48 hours following the training, participants completed a post-survey (T1). To evaluate the longer-term impact of the training, participants repeated the post-survey at 6 months post-training (T2).Results: Over a 1-year period, 598 individuals (78% women, 20% men; mean age = 45.5 years) received training in TIC. There was a significant increase between the T0 survey and the T1 post-survey in self-assessed knowledge and attitudes; systemwide knowledge and attitudes; training, support, interaction, and environment; and awareness of cultural background at work (P values < .001), but not safety and acceptance at work (P = .06). Open-ended qualitative responses on the T2 survey, which probed what specific policies and/or practices had been modified within the participant's organization, revealed improvement in several key themes (training, policy, and communication).Conclusions: This unique trauma-informed didactic training resulted isn persistent quantitative and qualitative change within individuals and organizations. Most notably, the training yielded greater confidence in utilizing TIC practices and systemic change at the organizational level. The results suggest that a 2-day training in TIC can transform organizational training, policy, and communications.

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been reported. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analysis), and EC (secondary analysis) using Neurite Orientation Dispersion and Density Imaging. Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion- weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure. Results: Higher PACAP levels in blood were associated with greater EC NDI (ß=0.31, q=0.034) and lower EC ODI (ß=-0.30, q=0.042) and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures. Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal- associated memory circuits.

Diversity of Participants in Williams Syndrome Intervention Studies.

PURPOSE: This study describes participant diversity in Williams syndrome (WS) intervention studies. METHODS: A literature search was conducted to identify prospective treatment studies including participants with WS. Data was extracted on the reporting of and information provided on age, sex, cognitive ability, socioeconomic status, race, and ethnicity. RESULTS: Eleven eligible articles were identified. Reporting rates of demographic factors varied considerably, with the highest rates for age and sex (100%) and the lowest reporting rates for race (18%) and ethnicity (9%). Combining demographic data from the two studies that reported on race and/or ethnicity (n = 33), 88% of participants were White. The combined participant mean age was 20.9 years. CONCLUSION: There is a low frequency of reporting on several demographic factors including socioeconomic status, race, and ethnicity in WS intervention studies. There is a need for increased representation of racial and ethnic minority groups, older participants, and more cognitively impaired patients in WS research.

Clozapine for treatment refractory catatonia in individuals with autism spectrum disorder: a retrospective chart review study.

BACKGROUND: Catatonia is increasingly recognized in individuals with autism spectrum disorder (ASD). Empirical data on treating catatonia in this population are limited. The purpose of this study is to provide naturalistic data on the use of clozapine for the treatment of catatonia in patients with ASD. RESEARCH DESIGN AND METHODS: Medical records of 12 individuals with ASD and catatonia who received treatment with clozapine were reviewed. Treatment response to clozapine was rated by assigning a retrospective Clinical Global Impression Improvement scale (CGI-I) score. RESULTS: Mean (SD) and median (IQR) age at initiation of clozapine treatment were 22.1 (7.7) and 20.4 (9.7) years, with a range of 10-39 years. Eleven of the 12 patients had received treatment with lorazepam prior to initiating clozapine and 9 of the 12 patients received concomitant treatment with lorazepam and clozapine. Eleven of the 12 patients (92%; 95% CI: 65%, 99%) responded to clozapine. All 12 patients remained on clozapine at the time of their most recent clinical note. All 12 patients (100%; 95% CI: 76%, 100%) experienced one or more adverse events, the most common of which was sedation (n = 11, 92%). CONCLUSIONS: Overall, clozapine was associated with a high response rate for the treatment of catatonia in patients with ASD. These naturalistic data support the use of clozapine for the treatment of catatonia in patients with ASD for whom lorazepam is either ineffective or partially effective.

Differential effects of the stress peptides PACAP and CRF on sleep architecture in mice.

Stress produces profound effects on behavior, including persistent alterations in sleep patterns. Here we examined the effects of two prototypical stress peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and corticotropin-releasing factor (CRF), on sleep architecture and other translationally-relevant endpoints. Male and female mice were implanted with subcutaneous transmitters enabling continuous measurement of electroencephalography (EEG) and electromyography (EMG), as well as body temperature and locomotor activity, without tethering that restricts free movement, body posture, or head orientation during sleep. At baseline, females spent more time awake (AW) and less time in slow wave sleep (SWS) than males. Mice then received intracerebral infusions of PACAP or CRF at doses producing equivalent increases in anxiety-like behavior. The effects of PACAP on sleep architecture were similar in both sexes and resembled those reported in male mice after chronic stress exposure. Compared to vehicle infusions, PACAP infusions decreased time in AW, increased time in SWS, and increased rapid eye movement sleep (REM) time and bouts on the day following treatment. In addition, PACAP effects on REM time remained detectable a week after treatment. PACAP infusions also reduced body temperature and locomotor activity. Under the same experimental conditions, CRF infusions had minimal effects on sleep architecture in either sex, causing only transient increases in SWS during the dark phase, with no effects on temperature or activity. These findings suggest that PACAP and CRF have fundamentally different effects on sleep-related metrics, and provide new insights into the mechanisms by which stress disrupts sleep.

Survey of quality and clarity of methods and results reporting in 1 year of intervention studies published in high-impact medical and psychiatric journals.

OBJECTIVE: We assessed how well articles in major medical and psychiatric journals followed best reporting practices in presenting results of intervention studies. METHOD: Standardised data collection was used to review studies in high-impact and widely read medical (JAMA, Lancet and New England Journal of Medicine) and psychiatric (American Journal of Psychiatry, JAMA Psychiatry, Journal of Clinical Psychiatry and Lancet Psychiatry) journals, published between 1 September 2018 and 31 August 2019. Two team members independently reviewed each article. MEASURES: The primary outcome measure was proportion of papers reporting consensus elements required to understand and evaluate the results of the intervention. The secondary outcome measure was comparison of complete and accessible reporting in the major medical versus the major psychiatric journals. RESULTS: One hundred twenty-seven articles were identified for inclusion. At least 90% of articles in both medical and psychiatric journals included sample size, statistical significance, randomisation method, elements of study flow, and age, sex, and illness severity by randomisation group. Selected elements less frequently reported by either journal type were confidence intervals in the abstract, reported in 93% (95% CI 84% to 97%) of medical journal articles and 58% (95% CI 45% to 69%) of psychiatric journal articles, and sample size method (93%, 95% CI 84% to 97% medical; 69%, 95% CI 57% to 80% psychiatric), race and ethnicity by randomisation group (51%, 95% CI 40% to 63% medical; 73%, 95% CI 60% to 83% psychiatric), and adverse events (94%; 95% CI 86% to 98% medical; 80%, 95% CI 68% to 88% psychiatric) in the main text. CIs were included less often in psychiatric than medical journals (p<0.004 abstract, p=0.04 main text, after multiple-testing correction). CONCLUSIONS: Recommendations include standard inclusion of a table specifying the outcome(s) designated as primary, and the sample size, effect size(s), CI(s) and p value(s) corresponding to the primary test(s) for efficacy.

Persistent Dissociation and Its Neural Correlates in Predicting Outcomes After Trauma Exposure.

OBJECTIVE: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma. METHODS: All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment. RESULTS: Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms. CONCLUSIONS: The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.

Prevalence and factors associated with overweight, obesity, and hypertension in a large clinical sample of adults with autism spectrum disorder.

Adults with autism spectrum disorder (ASD) are at risk for excess bodyweight and hypertension, yet the prevalence of and clinical predictors for these health conditions remain unknown. The objective of this study was to assess the prevalence of overweight, obesity, and hypertension in a large clinical sample of adults with a confirmed diagnosis of ASD and to examine potential clinical predictors. This retrospective chart review study included adult subjects (≥ 20 years) with ASD who had been seen within the past 5 years at a multidisciplinary developmental disorders clinic. Data collected from the electronic health record included age, sex, race and ethnicity, cognitive ability, language ability, body mass index (BMI), hypertension, and use of second generation antipsychotic medications (SGAs). Of 622 adults with a confirmed diagnosis of ASD potentially eligible for the study, 483 (78%) had one or more notes in their records from the past 5 years. Those with recent notes were 23% female, 89% White, and had a mean (SD) age of 28.1 (7.1) years. Overall prevalence estimates for adults represented by this predominantly male, White, and young clinical sample were 28% (95% CI 24%, 32%) for overweight (BMI 25-29.9 kg/m2), 35% (95% CI 31%, 40%) for obesity (≥ 30 kg/m2), and 11% (95% CI 9%, 15%) for hypertension. Controlling for age and sex, intellectual disability (ID) was significantly associated with BMI (p = 0.003) but not hypertension (p = 0.69); those with moderate or more severe ID had a mean BMI that was 2.26 kg/m2 (95% CI 0.96, 3.57) lower than those with no ID. Controlling for age and sex, neither language ability, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) subtype of autism, nor past or current use of SGAs were significantly associated with BMI or hypertension. The study identified a high prevalence of overweight and obesity in adults with ASD consistent with the prevalence of these medical comorbidities in the U.S. population.

A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder.

This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.5-45 mg/day) or placebo in a 2:1 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p < 0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22%: 74%) and 20% assigned to placebo (95% CI 2%: 60%) were rated "much improved" (CGI-I = 2) or "very much improved" (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine's safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.Clinical trial registration information: Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders; https://clinicaltrials.gov ; NCT01302964.

Parent Description of Anxiety in Angelman Syndrome.

Anxiety is being increasingly identified in Angelman syndrome (AS). Qualitative questions and quantitative assessments were used to evaluate for anxiety in 50 subjects with AS. In-person evaluations assessed behaviors concerning for anxiety and circumstances wherein they occurred. Caregivers completed anxiety and other behavioral rating scales. Caregiver responses were categorized and compared to items from anxiety rating scales. The most common behavioral manifestation of anxiety was "aggression." The most common circumstance was "separation from caregiver/parent." Subjects had elevated scores on anxiety, irritability and hyperactivity scales with lower mean scores among subjects with a maternal deletion. The Pediatric Anxiety Rating Scale best captured behaviors described by caregivers. Existing anxiety scales should be adapted for use in AS.

Repetitive Thoughts and Repetitive Behaviors in Williams Syndrome.

The purpose of the study was to characterize repetitive phenomena in Williams syndrome (WS). The parents of 60 subjects with WS completed the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) or Children's Y-BOCS, the Yale Global Tic Severity Scale, the Stereotyped Behavior Scale, and the Spence Children's Anxiety Scale-Parent Version. Nineteen males and 41 females participated in the study. Six subjects (10%) had obsessions only, six (10%) had compulsions only, and eleven (18%) had at least one obsession and at least one compulsion. None of the subjects had tics. Fifty subjects (83.3%) endorsed at least one stereotypy. Increased anxiety was associated with increased severity of obsessions, but not severity of compulsions or stereotypies.