Faculty Bibliography

OBJECTIVE/BACKGROUND/OBJECTIVE:Attention-Deficit/Hyperactivity Disorder (ADHD) is common in children. Many children with ADHD have chronic insomnia, which is associated with negative outcomes for the child and family and can worsen ADHD symptoms. Behavioural sleep interventions can be effective for children with ADHD and are the recommended first-line approach to management. However, many parents/carers may not have access to, or struggle to implement, interventions in practice. This study explored parents/carers views and experiences of: 1) behavioural sleep management strategies, 2) help-seeking for managing sleep problems and 3) perceptions about a potential digital sleep guide for managing sleep problems. PATIENTS/METHODS/METHODS:A qualitative study using semi-structured interviews of parents/carers of children with ADHD/ADHD traits and chronic insomnia symptoms (CIS). Participants were recruited via social media and purposively sampled for diverse characteristics. Interviews were conducted by telephone/videocall, recorded and transcribed verbatim. Data were analysed using inductive thematic analysis. RESULTS:Eighteen parents/carers took part; two themes and six subthemes were developed. Despite valuing behavioural sleep strategies, parents/carers noted many challenges to engaging with them, including perceiving these strategies to be both ineffective for children with ADHD and not easy to implement in the real world. They described that tiredness, exhaustion, ADHD symptoms and challenging behaviour make parent engagement with strategies difficult. Parents/carers welcomed digital support in principle, particularly because they perceived health professional support to be lacking. However, they noted that digital interventions must address their key support needs regarding flexibility, realistic expectations and a pragmatic approach, as well as comradeship, support and testimonials from other parents/carers. CONCLUSION/CONCLUSIONS:Tailored but flexible support and reassurance are necessary for parents/carers of children with ADHD and CIS. Digital support must validate parent/carer experiences and include experiences from other parents/carers.

INTRODUCTION/BACKGROUND:Serotonin (5-hydroxytryptamine [5-HT]) plays an important role in early development, and fetal 5-HT has been reported to arise from placental and maternal sources. Previous human studies have established an association between maternal 5-HT levels and neurodevelopmental outcomes in populations with autism. In this study, we analyze umbilical cord blood and placental 5-HT levels at birth to further investigate the relationship of gestational 5-HT levels with birth outcomes and offspring cognitive development. METHODS:Participants were enrolled in the Safe Passage Study conducted by the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network. Infant cord blood and placental samples were collected postdelivery, and 5-HT levels were measured using high-performance liquid chromatography-fluorometric analysis. The Mullen Scales of Early Learning (MSEL) assessed child development at 12 months. Associations between 5-HT levels and birth outcomes or developmental outcomes were assessed using linear regression models. RESULTS:No significant association was found between cord blood (n = 418) and placental (n = 89) 5-HT levels. Preterm birth was associated with lower cord blood 5-HT levels, and increasing gestational age among full-term infants was associated with higher cord blood 5-HT levels. Cord blood 5-HT was significantly associated with the Mullen Scales of Early Learning Composite Score, and follow-up analyses revealed a significant association between cord blood 5-HT and fine motor skills. No association was found between placental 5-HT and the Mullen composite score. CONCLUSION/CONCLUSIONS:To our knowledge, this study is the first to evaluate the relationship between placental 5-HT levels and cord blood 5-HT levels at birth. The lack of association suggests that cord blood 5-HT levels are likely to be a better index of fetal 5-HT exposure. Associations between cord blood 5-HT and child cognitive development are consistent with previous studies showing an association between maternal 5-HT levels and neurodevelopmental trajectories. Further research is needed to better characterize these relationships and to elucidate the distinct contributions of maternal, placental, and fetal 5-HT sources across developmental time points.

OBJECTIVE/UNASSIGNED:Obsessive-compulsive disorder (OCD) is one of the common mental disorders globally. However, there are limited studies on the prevalence of OCD and four other disorders categorized under obsessive-compulsive and related disorders, namely, hoarding disorder, excoriation disorder, body dysmorphic disorder, and trichotillomania. The authors sought to fill the epidemiological gap in the literature. METHODS/UNASSIGNED:criteria, were included. A Bayesian hierarchical linear mixed model was used to estimate the lifetime prevalence of OCD at the global, regional, and national levels, with estimates reported with 95% credible intervals. The authors examined the association between OCD prevalence and the Socio-demographic Index (SDI), and estimated age-specific point prevalence of OCD. RESULTS/UNASSIGNED:criteria. Lifetime prevalence of OCD was negatively correlated with SDI, indicating lower prevalence estimates in countries with higher SDI. The age-specific prevalence of OCD increased sharply in the teen years and peaked in the late 20s to early 30s. Point prevalence ranged across studies from 0.98% to 5.81% for hoarding disorder, from 2.33% to 7.68% for excoriation disorder, from 0.44% to 15.21% for body dysmorphic disorder, and from 0.0% to 2.12% for trichotillomania. CONCLUSIONS/UNASSIGNED:This study estimated the global prevalence of OCD according to diagnostic criteria, underscoring the role of diagnostic definitions in shaping epidemiological understanding.

AIMS/UNASSIGNED:Proximal junctional kyphosis (PJK) remains a major complication after surgery for adult spinal deformity (ASD). While postoperative alignment is a recognized modifiable risk factor, objective methods for selecting the upper instrumented vertebra (UIV), a key modifiable factor, are lacking. We aimed to determine whether preoperative sagittal alignment, specifically cervicothoracic alignment, predicts the risk of PJK, and whether this risk can be mitigated by UIV selection, focusing on factors available at the time of surgical planning. METHODS/UNASSIGNED:From a multicentre, prospective ASD registry, we identified patients who had undergone fusion to the sacrum or pelvis and had an upper (T1-T5) or lower thoracic (T9-L1) UIV, with a two-year or more radiological follow-up, excluding those with a previous fusion over more than four levels. The primary outcome was PJK within two years. Multivariable logistic regression modelled the risk of PJK by UIV region, preoperative C2-T9 pelvic angle (PA), age, sex, and pelvic incidence, testing for interaction between UIV region and C2-T9 PA. Adjusted absolute risk reduction (ARR) and number needed to be exposed (NNEB) were calculated. Multivariable linear regression estimated two-year patient-reported outcome measures, adjusting for baseline scores, age, UIV, and PJK. RESULTS/UNASSIGNED:A total of 627 patients across 20 centres were included (median age 66 years (IQR 59 to 70); 483 (77%) female). The UIV was lower thoracic in 380 (61%) and upper thoracic in 247 (39%) patients. PJK occurred in 149 (39%) lower thoracic and 38 (15%) upper thoracic UIV patients. There was a significant interaction (p = 0.028) between preoperative C2-T9 PA and UIV region. At a preoperative C2-T9 PA of 14° (cohort median), an upper thoracic UIV had an adjusted ARR of 36% and NNEB was 2.8. Females had an adjusted odds ratio of 1.62 (95% CI 1.03 to 2.59; p = 0.042) for PJK. CONCLUSION/UNASSIGNED:Worse preoperative sagittal malalignment, measured by C2-T9 PA, was associated with a higher risk of PJK and depended on UIV region. An upper thoracic UIV in patients with high preoperative C2-T9 PA may reduce PJK.

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.

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.

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.