Faculty Bibliography

OBJECTIVE:Autism spectrum disorder (ASD) is a neurodevelopmental condition with early-life origins. Maternal health conditions during pregnancy have been linked to autism risk, but most studies focus on single populations, limiting generalizability. We examined whether associations previously reported in a Danish registry-based study hold in a U.S. METHOD/METHODS:We analyzed electronic health records of children born between 2010 and 2017 at Kaiser Permanente Northern California (KPNC) and their mothers. Maternal diagnoses were classified as chronic or non-chronic, and associations with ASD in the child were assessed using Cox models, adjusting for sociodemographic factors, healthcare utilization, and comorbid maternal diagnoses. Methods were aligned with the Danish study for comparability. RESULTS:Among 224,353 children in the KPNC cohort, 5,448 (2.4%) were diagnosed with autism. Of the 42 maternal diagnoses significantly associated with autism in Denmark, 38 were evaluable in KPNC, and 18 remained statistically significant after adjustment. Most associations had point estimates consistent with the Danish study, particularly psychiatric and cardiometabolic conditions. CONCLUSION/CONCLUSIONS:Despite demographic and healthcare differences, 35 of the 38 associations found in the Danish study replicated qualitatively (direction of effect) in the U.S. cohort, suggesting robust cross-setting relevance. Further research is needed to explore underlying mechanisms and effect modifiers.

Mental disorders are increasingly understood as disorders of brain development. Large and heterogeneous samples are required to define generalizable links between brain development and psychopathology. To this end, we introduce Reproducible Brain Charts (RBC), an open resource that integrates data from 5 large studies of brain development in youth from three continents (N = 6,346). Bifactor models were used to create harmonized psychiatric phenotypes, capturing major dimensions of psychopathology. Following rigorous quality assurance, neuroimaging data were carefully curated and processed using consistent pipelines in a reproducible manner. Initial analyses of RBC emphasize the benefit of careful quality assurance and data harmonization in delineating developmental effects and associations with psychopathology. Critically, all RBC data-including harmonized psychiatric phenotypes, unprocessed images, and fully processed imaging derivatives-are openly shared without a data use agreement via the International Neuroimaging Data-sharing Initiative. Together, RBC facilitates large-scale, reproducible, and generalizable research in developmental and psychiatric neuroscience.

Iron plays a vital role in early brain development, supporting critical processes such as myelination, dendritogenesis, and neurotransmitter synthesis. The perinatal period marks a crucial transition from the intrauterine to the extrauterine environment, requiring significant brain adaptation to new stimuli and metabolic demands. However, tight spatiotemporal resolution capturing the timing and sequence of brain iron changes surrounding this critical transition has yet to be achieved. Leveraging a longitudinal perinatal cohort with 147 multi-echo MRI scans spanning from 25 to 60 post-conceptual gestational weeks, we mapped brain iron growth trajectories with R2* estimation across fetal, newborn and neonatal periods. We also examined whether sex, gestational age at birth, and birth weight influence R2* developmental trajectories. We found that parietal and superior temporal regions predominately show linear growth trajectories throughout the perinatal period across birth, while the occipital cortex, the temporal pole, inferior temporal regions and a subset of frontal regions exhibit non-linear trends. For most of the non-linear trajectories, growth rates peak around 40 weeks, highlighting the critical window of birth transition for brain R2* change. These results provide the first longitudinal insights into R2* development across birth, uncovering distinct regional growth patterns that may align with different phases of neurodevelopment.

BACKGROUND:Adolescents in low- and middle-income countries (LMICs) face significant mental health challenges, yet their perspectives are often underrepresented in the design of preventive strategies. Co-design approaches, such as human-centered design (HCD), offer a promising way to tailor interventions and implementation strategies to adolescents’ needs and local context. In LMICs, these methods require careful adaptation to address resource constraints, limited design literacy, and cultural norms. This study documents how HCD was adapted to engage adolescents in northern Ghana as co-designers of school-based mental health preventive strategies. METHODS:Guided by the first two phases of HCD, we conducted two workshops with 24 students from 12 public senior high schools in Tamale, Ghana. Workshop 1 (Inspiration) used structured, case-based discussions informed by the Consolidated Framework for Implementation Research (CFIR) to explore adolescents’ perspectives on mental health. Workshop 2 (Ideation) used interactive choice-based activities to elicit youth-generated strategies. To align with cognitive and sociocultural factors, we incorporated scaffolded facilitation, hands-on activities, and peer-led engagement. Qualitative data from facilitator notes, artifacts, and audio-confirmed summaries were synthesized using structured rapid qualitative analysis. RESULTS:Adolescents identified key mental health concerns, including stigma, peer and family influences, and fears about confidentiality. Gender-specific discussions revealed culturally rooted concerns, such as peer pressure and substance use among boys and limited support-seeking among girls. Adolescents prioritized five school strategies: teacher training, curricular integration, mentorship programs, activities that promote positive thinking and mindfulness, and entertainment-based mental health education. Youth demonstrated a conceptual shift from viewing mental health as an individual problem to a shared responsibility across schools and communities. Formation of an Adolescent Advisory Board reflected youth interest in sustained leadership and co-design. CONCLUSIONS:Contextualized co-design methods can meaningfully engage adolescents in LMIC settings and support the development of culturally grounded, feasible, and youth-prioritized mental health strategies. Structured facilitation enhances both the inclusivity and authenticity of adolescent engagement. This study contributes to implementation science by presenting a replicable co-design framework with policy relevance and providing a foundation for multilevel intervention development in resource-constrained educational systems. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12889-025-25012-0.

Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane's RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review (https://ebipsyche-database.org/). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control (k = 11; SMD=-0.85 [-1.09; -0.60]; I²=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (k = 8; SMD=-0.62 [-0.97; -0.28]; I²=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMD_MDMA=-1.18 [-2.04; -0.32]; I²=0 %; k = 2; GRADE=low and SMD_serotonergic=-0.88 [-1.70; -0.06]; I²=54 %;k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (k = 6; RR=1.42 [0.89; 2.26]; I²=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RR_MDMA=0.74 [0.32; 1.72]; RR_serotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.

Advanced EEG technology has revealed that epileptiform activity occurs more frequently in Alzheimer's disease (AD) than previously recognized, prompting debate over the utility of EEG in AD diagnostics. Yet, unlike epilepsy, epileptiform activity is not always observed in AD, leading to skepticism. Historically, this absence has been attributed to limited recording depth or insufficient recording duration. We tested an alternative hypothesis that certain types of epileptiform activity, specifically high-frequency oscillations (HFOs, defined as 250-500Hz fast ripples), inhibit interictal spikes (IIS), which are currently used to assess hyperexcitability clinically. We recorded wideband (0.1-500Hz) hippocampal local field potentials in three AD (Tg2576, Presenilin 2^-/-, Ts65Dn Down syndrome model) and two epilepsy (intrahippocampal kainic acid, pilocarpine) mouse models during wakefulness and sleep. In both AD and epilepsy, HFOs consistently outnumbered IIS across behavioral states, age and recording contact. However, IIS and HFOs showed divergent relationships: a negative correlation between their rates was observed only in AD, in contrast to a positive correlation in epilepsy. HFOs preceded IIS at much shorter intervals in epilepsy than in AD. Co-occurrence of IIS with ripples did not differ between AD and epilepsy. These findings reveal a novel dissociation between clinically-relevant EEG biomarkers in AD and epilepsy. In AD, HFOs may inhibit IIS, which could lead to underestimation of hyperexcitability and hinder patient stratification for anti-seizure therapies. While non-invasive HFO detection remains challenging, we stress the need for wideband EEG/MEG, particularly in AD, to assess the full extent of hyperexcitability and biomarker interactions that would otherwise remain undetected.

Interoceptive accuracy, the ability to correctly perceive internal body signals such as heartbeats, has been empirically and theoretically linked to stress. However, issues with the measurement of both interoceptive accuracy and stress have led to lack of clarity regarding this relationship. This systematic review and meta-analysis aimed to clarify whether interoceptive accuracy is associated with different facets of stress, including - physical, cognitive and self-reported stressors and the physiological stress response. A systematic search identified 2014 abstracts. Twenty-eight authors were contacted to request data for eligible studies, which yielded a final sample of 20 studies. Results revealed a positive association between heartbeat counting task (HCT) performance and acute physical stressors, and a negative association between HCT performance and physiological stress responses. No significant relationships were observed between stress and interoceptive accuracy assessed by the heartbeat discrimination task. While these findings offer tentative support for stress-interoceptive accuracy associations, they must be interpreted with caution given substantial heterogeneity in stress measures, limited use of interoception tasks beyond the HCT, and ongoing concerns regarding task validity. Implications for future research and methodological recommendations are discussed.