Faculty Bibliography

OBJECTIVE:To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above. BACKGROUND:Preliminary evidence suggests CBD may ameliorate challenges associated with ASD. Whether CBD benefits pediatric ASD without accompanying intellectual or language impairment remains unknown. METHODS:, 100 mg/mL) at 3, 6, or 9 mg/kg/day using a Bayesian optimal interval dosing design. The primary endpoint was the CBD dose associated with the highest response rate (i.e., Clinical Global Impression Scale-Improvement [CGI-I] score = 1 or 2) on a target symptom domain designated individually based on informant report, standardized scales, and clinical observation. Secondary endpoints were effect sizes of changes from baseline in measures assessing ASD core and associated symptoms, and global functioning. Adverse events (AEs) were assessed weekly. Plasma CBD levels and clinical labs were obtained at the final visit. RESULTS:= 1.36, 95% CI [0.78-1.93]).Of 222 reported AEs, 27 unique AEs were considered treatment-related. Most AEs (93%) were mild and expected (82%); none was severe. The most frequent related AEs were increased salivation (30%), increased sleep duration (39%), sleepiness/sedation (26%), increased dream activity (35%), and polyuria (22%). Vital signs, physical exams, weight, liver function tests, and complete blood counts were unaffected. CBD plasma levels did not correlate with response. CONCLUSIONS:In this preliminary study, CBD was well tolerated; AEs were mild-moderate. Mean SRS2-T and subscores decreased significantly with large effect sizes, shifting from the severe to the moderate range. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier NCT03900923.

INTRODUCTION/UNASSIGNED:Narrative, or storytelling, is a primary form of social communication. Prior work has documented differences in narrative in individuals with autism spectrum disorder (ASD), but predominantly focused on English-speaking Western countries. Given the internalization of cultural values and conventions shapes narrative, the extent to which environmental (i.e., cultural and linguistic) factors may interact with ASD to influence the narrative ability remains unclear. The current study applied a cross-cultural approach to investigate narrative quality in ASD between a Western (United States) culture and an Eastern [Chinese (Hong Kong)] culture. Given that visual attention and exploration inform one's experiences and consequently storytelling, visual attention during narration was examined to unravel underlying mechanisms contributing to narrative. METHODS/UNASSIGNED:Participants included 56 autistic individuals (US-ASD) and 49 non-autistic controls (US-control) from the US who were native English speakers, as well as 24 autistic individuals (HK-ASD) and 52 controls (HK-control) from the Hong Kong SAR, China (HK), who were native Cantonese speakers, with age matched across groups. Participants narrated a wordless picture book presented on an eye-tracker, with narrative quality and dynamic gaze patterns examined. RESULTS/UNASSIGNED:Group comparisons revealed that autistic individuals from both cultures missed key story components and exhibited elevated rigid gaze patterns towards social stimuli. Cultural variations were also demonstrated, with US-ASD group, but not HK-ASD group, narrating with fewer descriptions and causal attributions of characters' thoughts/emotions. Further, correlational analyses revealed the association between decreased social attention and fewer descriptions of characters' thoughts/emotions across diagnostic and cultural groups. DISCUSSION/UNASSIGNED:Together, the findings highlight a difficulty in overall narrative structure and a pattern of regressive/rigid social attention present in ASD across cultures. In contrast, the difficulty in usage of cognitive/emotional terms and causal attributions in ASD appear to be culturally influenced, and were only present in US-ASD. Gaze-narrative associations detected across diagnosis and cultures emphasize the importance of extrapolating underlying mechanistic processes contributing to social language use in general and in ASD. Findings implicate key features of narrative ability that may be more or less malleable to cultural influences, with implications for the biological underpinnings of ASD and culturally-centered clinical practices.

BACKGROUND:Poor persistence and adherence to attention-deficit/hyperactivity disorder (ADHD) medication is a significant barrier to effective long-term care, particularly during adolescence, yet age-specific and sex-specific trajectories remain poorly characterised. OBJECTIVE:To characterise medication initiation, discontinuation and long-term adherence patterns for children and adolescents diagnosed with ADHD in a real-world setting. METHODS:A nationwide retrospective cohort study, including 8961 children and adolescents (aged <18 years) with a new ADHD diagnosis in child and adolescent mental health services between 1 January 2010 and 31 December 2012, with follow-up until 31 December 2021. Main outcomes were medication initiation rates; time to first medication discontinuation, analysed using Kaplan-Meier estimates and restricted mean survival time at 1 year and longitudinal adherence, measured by the proportion of days covered over 9 years. FINDINGS/RESULTS:Of the 8961 individuals in the cohort (mean age at diagnosis, 12 years; 69% male), 6661 (74.3%) initiated medication, with a median time from diagnosis to initiation of 106 days (IQR 17-231); 55% initiated within 90 days. Discontinuation increased significantly with age; adolescents aged 15-17 years remained on treatment for 31.9 fewer days (95% CI -40.8 to -23.1; p<0.001) in the first year compared with children aged 5-11 years. Females also discontinued significantly earlier than males (difference -13.2 days; 95% CI -19.8 to -6.5; p<0.001). Longitudinal analysis confirmed that older age at initiation and female sex were associated with a significantly steeper decline in medication coverage over time. CONCLUSIONS:Discontinuation and low adherence to ADHD medication were common and increased substantially through adolescence, with females at higher risk of early cessation. CLINICAL IMPLICATIONS/CONCLUSIONS:Late adolescence warrants closer clinical monitoring and shared decision-making to support appropriate treatment continuation or well-informed discontinuation, particularly for older adolescents and females. Integrating structured transition planning and attention to sex-specific barriers may help reduce avoidable non-adherence during this high-risk period.

In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and schizophrenia spectrum disorders (SSDs). In this narrative review, we examine the historical and theoretical relationship between psychedelic drugs and SSDs, including the origins of the psychotomimetic hypothesis. For key psychedelic compounds, we review their phenomenological manifestations in relation to the experiential alterations characteristic of SSDs, revealing both areas of overlap and important qualitative differences that challenge the uniform psychotomimetic classification. We also review putative neural mechanisms underlying altered experiential states associated with psychedelic use and SSDs, with attention to serotonergic, dopaminergic, and glutamatergic contributions. Clinical evidence demonstrates that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, though the magnitude of these risks remains inadequately quantified. However, phenomenological and mechanistic distinctions suggest that potential therapeutic applications may exist for carefully selected symptoms (negative symptoms, depression) in stable patients using low-dose, controlled approaches. Based on published work, we provide recommendations regarding psychosis-related risk and potential avenues for the treatment of SSDs as psychedelics gain traction as therapeutics.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in  children and young people worldwide. Robust estimates of its incidence, prevalence, and burden are essential for informing public health policy and planning. Using data from the Global Burden of Disease Study 2021 (GBD 2021), this global population-based analysis assessed ADHD among individuals under 20 years of age across 204 countries and territories from 1990 to 2021. The study examined incidence, prevalence, and disability-adjusted life years (DALYs) associated with ADHD. In 2021, there were an estimated 46,890,733 (95% uncertainty interval [UI]: 32,136,904-67,271,064) prevalent cases and 4,111,621 (2,775,203-5,954,941) incident cases globally in individuals under 20 years. ADHD accounted for 574,979 (294,277-977,557) DALYs, with a global prevalence rate of 1.78% (1.22-2.55%) and an incidence rate of 0.16% (0.11-0.23%). The global DALY rate was 21.8 (11.2-37.1) per 100,000 population. Prevalence and incidence were highest in Australia, with rates of 5.62% (4.16-7.46%) and 0.49% (0.34-0.66%), respectively. Between 1990 and 2021, global prevalence and incidence rates decreased modestly by 6.0 and 5.81%, respectively. Across all GBD regions, prevalence was higher in males than females (2.52 vs 0.99%) and increased with higher socio-demographic index levels. Overall, the GBD 2021 study provides the most comprehensive global estimates of ADHD burden in young people. These findings are important for guiding policymakers and stakeholders, although potential methodological limitations suggest that the prevalence, incidence, and burden of ADHD may be underestimated.

INTRODUCTION/BACKGROUND:Sexual and gender minority (SGM) populations experience health disparities linked to minority stress (socially-based stressors), including proximal (e.g., SGM internalized stigma) and distal stressors (e.g., negative bias from non-SGM people toward SGM individuals). We synthesized and evaluated the effectiveness of interventions reducing proximal and distal SGM stress. METHODS:We followed PRISMA and Joanna Briggs Institute guidelines (CRD42024604568). Five databases were searched and eligible studies evaluated interventions reducing minority stress with sufficient data for effect size estimation. We estimated three-level multivariate meta-regression models for distal and proximal minority stress using restricted maximum likelihood estimation and robust standard error estimates. RESULTS:Fifty-one studies (31 distal, 20 proximal) with 11253 participants (SGM n = 3168) were included. Distal stress interventions yielded a null-to-small pooled effect (g = 0.185, 95% CI = 0.078, 0.292). Psychological interventions had a small effect (g = 0.361, 95% CI = 0.178, 0.544) and outperformed psychoeducation and social contact-based interventions (-0.257 < β < -0.221, p < 0.05). For proximal minority stress, although the overall pooled effect was nonsignificant (g = 0.071, 95% CI = -0.154, 0.297) the intervention × outcome interaction was (Wald Q = 4.661, p = 0.005). Narrative therapy targeting identity affirmation showed a large pooled effect (g = 1.846, 95% CI = 1.032, 2.659). Pairwise contrasts using this intervention-outcome combination as reference indicated that psychoeducation and psychological interventions had greater effects on internalized stigma and perceived social support (2.172 < β < 2.719, p < 0.05). CONCLUSION/CONCLUSIONS:Psychological interventions may reduce both proximal and distal stress. However, aligning interventions to specific minority stressors may yield greater benefit on SGM populations' health.

INTRODUCTION/BACKGROUND:A variety of rating scales are currently being used to assess symptom severity and quantify symptoms change in attention-deficit/hyperactivity disorder (ADHD) research and clinical practice. This poses difficulties in interpreting scores from different scales in clinical practice and synthesizing data from studies using different scales. We aimed to develop algorithms for converting scores across the ADHD scales most often used in randomized controlled trials (RCTs) of ADHD medications in children/adolescents and adults, and to develop an online tool for implementing the algorithms. METHODS: RESULTS:We linked six commonly used ADHD scales, such as the ADHD Rating Scale (ADHD-RS-IV; investigator-rated) and the Conners' Parent Rating Scale (CPRS-R:S). Spline models most frequently yielded the lowest prediction error, outperforming alternative conversion algorithms for absolute scores in 6 out of 12 univariable models and 8 out of 12 multivariable models. The tool for scores conversion is available at ADHD_Scale_Conversion_Tool. CONCLUSIONS:Our linkage algorithms enable the comparison and harmonization of findings across studies using different ADHD rating scales. Translating scores across scales improves the interpretability of research findings, facilitates future evidence synthesis across studies, and may support clinical practice. Our online tool supports the practical uptake of our results.

Much has been elucidated about the neurobiological effects of early childhood trauma and its transgenerational transmission, although its integration into psychodynamic therapy has been challenging. Here we focus on a common area of interest to both areas-emotion and cognition rooted in past trauma experiences and how these experiences produce maladaptive behaviors transmitted to the next generation through parenting behaviors. We explore two mammalian research paradigms of early-life trauma explicitly within attachment, and transmission of transgenerational pathology through the caregiver to the offspring. We suggest that understanding the neurobiology through this mammalian nonhuman research can provide, in part, an understanding for the complex psychodynamic thought processes seen in adulthood, particularly as the mother begins to raise her own child. Specifically, while cognition and complex conscious and unconscious thoughts are characteristic of the human condition following early-life trauma, the mother-infant attachment system is a phylogenetically preserved system with some basic characteristics seen across species. We outline how embracing both the cognition and preserved trauma neural programing within attachment may provide some insight into cases, especially for the parent-child social interactions well documented to program the brain. Using mother-infant attachment, we suggest there is an area of convergence between clinical psychodynamic focus and basic research in brain function and mechanisms. Focusing on this convergence may provide a unique viewpoint to psychodynamics to supplement diagnosis and treatment.