Faculty Bibliography

BACKGROUND:Depression rates are higher in women, especially during periods of hormonal fluctuation. Reproductive system disorders (RSDs), which often disrupt hormonal balance, may contribute to this mental health burden. Despite their prevalence and significant health implications, the link between RSDs and depression remains underexplored, leaving a gap in understanding these women's mental health risks. METHODS:Using Danish nationwide health registers (2005-2018), we conducted a cohort study of 2,295,824 women aged 15-49, examining depression outcomes in 265,891 women diagnosed with 24 RSDs, including endometriosis, polycystic ovary syndrome, and pain-related diagnoses. For each RSD, age-matched controls were selected. We calculated incidence rates, incidence rate ratios, and prevalence proportions of depression diagnoses or antidepressant use around RSD diagnosis. RESULTS:Across all RSD subtypes, women demonstrated higher rates of depression both before and after diagnosis, with a peak within the year following diagnosis. Incidence rate ratios within 1 year of RSD diagnosis ranged from 1.15 (95% confidence interval [CI] 1.06-1.25) to 2.09 (95% CI 1.98-2.21), depending on RSD subtype. Elevated depression prevalence was observed 3 years before diagnosis, suggesting mental health impacts may have preceded clinical RSD identification. CONCLUSIONS:This study reveals a striking association between RSDs and depression. Women with RSDs are more likely to suffer from depression, before and after RSD diagnosis, highlighting the need for integrated mental health screening and intervention. With over 10% of women affected by RSDs, addressing this overlooked mental health burden is imperative for improving well-being in a significant portion of the population.

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.

Recent medical advances are allowing more youth with neuromuscular disorders to live into adulthood, thus increasing the necessity to transition youth from pediatric to adult medical care. Examining salient factors and processes for successful transition planning from pediatric to adult medical care in youth with neuromuscular disorders is a nascent field of study. The current study aims to address the key quality improvement question of identifying factors to consider when planning for transition by exploring the views of youth with neuromuscular disorders, caregivers, and providers within a multidisciplinary clinic regarding current care transition practices via quantitative and qualitative approaches. Both qualitative and quantitative results highlighted patient-endorsed importance of transition and emphasized the need for future tailored supports to facilitate gleaning skills for transition. Overall, this study offers valuable insights from patients, parents, and providers about challenges and best practices involved in transition planning for young adults with neuromuscular disorders.

STUDY QUESTION/OBJECTIVE:Is there an association between infertility diagnosis and long-term adult-onset psychiatric conditions in women? SUMMARY ANSWER/CONCLUSIONS:Infertility diagnosis in women is linked to higher risks of mood disorders, anxiety- and stress-related disorders, and behavioral syndromes with physical components, but not schizophrenia or other psychotic disorders, particularly notable from 9 years after the first infertility diagnosis. WHAT IS KNOWN ALREADY/BACKGROUND:Infertility, especially in women, is associated with major mental health challenges around the time of diagnosis. However, the long-term connection with a wide range of psychiatric disorders is largely unknown. STUDY DESIGN, SIZE, DURATION/METHODS:This study employed a matched-pair design within the UK Biobank (UKB) cohort, including 3893 females with a diagnosis of infertility and 15 603 matched female controls, totaling 19 496 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:Female UKB participants with a diagnosis of infertility were matched to females without the diagnosis in a 1:4 ratio based on year of birth, index of deprivation of their residency area, and primary care data linkage status. The diagnosis of female infertility was identified by the first occurrence of a primary or secondary diagnosis in either primary care or hospital records. Additional analyses explored interactions between infertility diagnosis and both miscarriage and childbearing status on psychiatric conditions. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:Diagnosis of infertility was associated with higher risks of mood disorders, anxiety- and stress-related disorders, and behavioral syndromes with physical components, but not with schizophrenia or other psychotic disorders. The most notable increases in the risk of psychiatric diagnoses were observed 9 years after the first infertility diagnosis. No significant interactions were found between infertility diagnosis and either miscarriage or childbearing status on psychiatric conditions. Sensitivity analysis confirmed the robustness of these associations across different data sources for infertility diagnosis and psychiatric condition ascertainment. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The study's limitations include the racial homogeneity and the overall healthier status of the UKB cohort compared to the general UK population and the potential underestimation of associations due to misclassification of subfecund women. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:These results emphasize the need for integrated mental health support in infertility care and long-term monitoring of infertility patients for psychiatric risks. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:None. No competing interests were declared. TRIAL REGISTRATION NUMBER/BACKGROUND:n/a.

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.