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Department/Unit:Child and Adolescent Psychiatry

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In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders - a population-based cohort study and meta-analysis

Bang Madsen, Kathrine; Larsson, Henrik; Skoglund, Charlotte; Liu, Xiaoqin; Munk-Olsen, Trine; Bergink, Veerle; Newcorn, Jeffrey H; Cortese, Samuele; Lichtenstein, Paul; Kuja-Halkola, Ralf; Chang, Zheng; D'Onofrio, Brian; Hove Thomsen, Per; Klungsøyr, Kari; Brikell, Isabell; Garcia-Argibay, Miguel
The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HRadjusted 0.95, 95% CI 0.82-1.11), ADHD (HRadjusted 0.92, 95% CI 0.78-1.08), or ASD (HRadjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.
PMID: 40148550
ISSN: 1476-5578
CID: 5817072

Prevalence and Geographic Variation of Serious Mental Illness Among Young Adults Enrolled in Medicaid in New York State

Rodwin, Aaron H; Layman, Deborah; Finnerty, Molly; Patel, Sadiq Y; Jeong, Junghye; Chen, Qingxian; Munson, Michelle R
PURPOSE/OBJECTIVE:To estimate the prevalence and geographic variation of serious mental illness (SMI) among young adults enrolled in Medicaid and to identify individual and community-level factors associated with SMI. METHODS:We used New York Medicaid data for over 1.6 million young adults aged 18-34 years with continuous Medicaid enrollment from April 2021 through March 2022. We merged 3 additional county and zip code-level datasets, including the Distressed Communities Index, Area Health Resource File, and New York homelessness data. We used descriptive analyses, data visualization methods, and multivariable logistic regression to estimate the prevalence of SMI and identify individual- (sex, race and ethnicity, age, disability aid, and homelessness) and community-level (geography, community distress, number of hospital beds, and community mental health centers per capita) factors associated with SMI. RESULTS:The 12-month prevalence of SMI was 8.3% in New York State, with wide geographic variation by zip codes, ranging from 0% to 39%. Young adults identifying as Asian, Black, and Latinx (compared to White), and those living in zip codes with the most community distress were associated with lower odds of SMI, odds ratios (OR) ranged from 0.47 (Asian) (95% confidence interval [CI] [0.46-0.49]) to 0.95 (Latinx) (CI [0.93-0.97]). Young adults identifying as female (compared to male), receiving disability, experiencing homelessness, and rural residence were associated with higher odds of SMI, ORs ranged from 1.64 (female) (95% CI [1.62-1.66]) to 5.49 (homelessness) (95% CI [5.33-5.66]). DISCUSSION/CONCLUSIONS:SMI prevalence varies by individual- and community-level factors, including homelessness and rural residence, signaling the need for specific interventions and policies.
PMID: 40100185
ISSN: 1879-1972
CID: 5813252

The neural basis of dialectical thinking: recent advances and future prospects

Hu, Xiaomeng; Ma, Han-Qing; Tian, Ying-Qi; Hu, Yong-Heng; Chen, Sylvia Xiaohua; Castellanos, Francisco Xavier; Peng, Kai-Ping; Yan, Chao-Gan
Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored. This review synthesizes current neuroscientific findings and introduces the dialectical-integration network (DIN) hypothesis, which identifies key brain regions such as the dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), dorsal lateral prefrontal cortex (DLPFC), nucleus accumbens, basal ganglia, and amygdala. These regions, along with networks like the default mode network (DMN) and frontoparietal network (FPN), facilitate holistic reasoning, conflict resolution, and sensory-emotional integration. The psychological benefits of dialectical thinking include enhanced cognitive flexibility, reduced emotional extremes, and improved conflict resolution. This review emphasizes the need for cross-cultural and neuroscientific research to explore the principle of change, a core aspect of dialectical cognition. By bridging cultural psychology and cognitive neuroscience, this work offers theoretical and methodological insights into culturally shaped cognitive styles, with practical applications in education, mental health, and intercultural communication. The DIN model provides a framework for future research on dynamic neural interactions supporting dialectical thinking.
PMID: 40068932
ISSN: 2191-0200
CID: 5808402

Exploring Serotonergic Psychedelics as a Treatment for Personality Disorders

Carrithers, Brennan M; Roberts, Daniel E; Weiss, Brandon M; King, Jacob D; Carhart-Harris, Robin L; Gordon, Alexandra R; Pagni, Broc A; Moreau, Miltiadis; Ross, Stephen; Zeifman, Richard J
Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.
PMID: 40081794
ISSN: 1873-7064
CID: 5808842

Large-scale evidence of a general disease ('d') factor accounting for both mental and physical health disorders in different age groups

Sun, Hongyi; Carr, Hannah; Garcia-Argibay, Miguel; Cortese, Samuele; Solmi, Marco; Golm, Dennis; Brandt, Valerie
BACKGROUND:It is unknown whether there is a general factor that accounts for the propensity for both physical and mental conditions in different age groups and how it is associated with lifestyle and well-being. METHODS:factor, lifestyles, and well-being was further explored. RESULTS:factor scores significantly correlated with lifestyle and well-being, suggesting healthier lifestyles were associated with a reduced likelihood of physical and mental health comorbidities, which in turn improved well-being. CONCLUSIONS:Contrary to the traditional dichotomy between mental and physical conditions, our study showed a general factor underlying the comorbidity across mental and physical diseases, related to lifestyle and well-being. Our results inform the conceptualization of mental and physical illness as well as future research assessing risk and pathways of disease transmission, intervention, and prevention. Our results also provide a strong rationale for a systematic screening for mental disorders in individuals with physical conditions and vice versa, and for integrated services addressing multimorbidity.
PMID: 40066566
ISSN: 1469-8978
CID: 5808292

Publisher Correction: Adapting the Parent Connector program for caregivers of adults with SMI: the Family Connector experience

Cervantes, Paige E; Gendler, Charlotte; Markowitz, Lori; Rose, Meggin; Shorter, Priscilla; Mason, Sally; Hernandez, Tanya; Hoagwood, Kimberly E
PMID: 40055435
ISSN: 2731-4251
CID: 5807982

Advancing the evidence base for child and adolescent psychopharmacology [Editorial]

Cortese, Samuele; Moreno, Carmen
This editorial focuses on the seven studies published in the BMJ Mental Health topic collection Advances in Clinical Psychopharmacology in Children and Young People. Collectively, these articles provide evidence that informs key steps in the psychopharmacological management of children and adolescents with mental health or neurodevelopmental conditions. Papers in this collection contribute to strengthen evidence-based psychopharmacological practice. We look forward to further developments in the field, supported by adequate research funding.
PMCID:11877239
PMID: 40032555
ISSN: 2755-9734
CID: 5809662

Familial confounding in the associations between maternal health and autism

Khachadourian, Vahe; Arildskov, Elias Speleman; Grove, Jakob; O'Reilly, Paul F; Buxbaum, Joseph D; Reichenberg, Abraham; Sandin, Sven; Croen, Lisa A; Schendel, Diana; Hansen, Stefan Nygaard; Janecka, Magdalena
Evidence suggests that maternal health in pregnancy is associated with autism in the offspring. However, most diagnoses in pregnant women have not been examined, and the role of familial confounding remains unknown. Our cohort included all children born in Denmark between 1998 and 2015 (n = 1,131,899) and their parents. We fitted Cox proportional hazard regression models to estimate the likelihood of autism associated with each maternal prenatal ICD-10 diagnosis, accounting for disease chronicity and comorbidity, familial correlations and sociodemographic factors. We examined the evidence for familial confounding using discordant sibling and paternal negative control designs. Among the 1,131,899 individuals in our sample, 18,374 (1.6%) were diagnosed with autism by the end of follow-up. Across 236 maternal diagnoses we tested (prevalence ≥0.1%), 30 were significantly associated with autism after accounting for sociodemographic factors, disorder chronicity and comorbidity, and correction for multiple testing. This included obstetric, cardiometabolic and psychiatric disorders (for example, diabetes in pregnancy (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.31) and depression (HR 1.49, 95% CI 1.27-1.75)), previously shown to be associated with autism. Family-based analyses provided strong evidence for familial confounding in most of the observed associations. Our findings indicate pervasive associations between maternal health in pregnancy and offspring autism and underscore that these associations are largely attributable to familial confounding.
PMID: 39891002
ISSN: 1546-170x
CID: 5781342

Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life

Bellato, Alessio; Perrott, Nadia J; Marzulli, Lucia; Parlatini, Valeria; Coghill, David; Cortese, Samuele
OBJECTIVE:We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and nonstimulants. METHOD/METHODS:February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multilevel meta-analytic models were conducted with R 4.3.1. RESULTS:We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedge's g = 0.51, 95% CI = 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults. CONCLUSION/CONCLUSIONS:In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and nonstimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and nonpharmacological interventions is likely to further improve QoL in people with ADHD. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:From a prior dataset of a network meta-analysis, 17 randomized controlled trials (RCTs) were included in a meta-analysis to investigate if attention-deficit/hyperactivity disorder (ADHD) medication improves quality of life (QoL) in people with ADHD. The analysis showed that medications such as amphetamines, methylphenidate, and atomoxetine improved QoL compared to placebo, with moderate effect sizes. This study underscores the importance of ADHD medications, both stimulants and nonstimulants, not only in alleviating core ADHD symptoms but also in enhancing overall QoL for individuals with ADHD. STUDY PREREGISTRATION INFORMATION/UNASSIGNED:Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/; qvgps.
PMID: 38823477
ISSN: 1527-5418
CID: 5809572

Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review

Besag, Frank M C; Vasey, Michael J; Roy, Sulagna; Cortese, Samuele
BACKGROUND:Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature. The aim of this review is to evaluate the evidence in the published literature for Raynaud syndrome associated with medication for ADHD. METHODS:We systematically searched PubMed and Embase from inception to 12 June 2024 for articles published in English describing cases of RS in individuals treated with stimulant medication, atomoxetine, guanfacine or clonidine. Identified cases were assessed against the Naranjo Adverse Drug Reaction Scale criteria to determine the probability of a causal relationship with the medication. RESULTS:The initial search identified 197 articles. A total of 61 cases were identified from 15 case reports, 5 case series, 1 retrospective case-control study, and 1 retrospective cohort study. No randomised, controlled studies were identified. Implicated medications included methylphenidate, (dex)amfetamine and, more rarely, atomoxetine. Most cases were mild and resolved within weeks of discontinuation, dose reduction or switch to an alternative medication. A few cases associated with systemic disease were reported, leading to ulceration, gangrene and the need for amputation or revascularisation in some individuals. Assessment of 28 cases using the Naranjo criteria suggested a 'possible' causative role of ADHD medication in 13 cases, a 'probable' role in 13 cases and a 'definite' role in two cases. CONCLUSIONS:Due to the uncontrolled nature of all but one of the available studies, a causal relationship between medication for ADHD and RS could not be determined reliably. However, in view of the possibility of severe sequelae, albeit in rare cases, routine monitoring for signs of RS is recommended in individuals treated with CNS stimulants or atomoxetine, especially when initiating treatment or increasing the dose. Large database studies in which individuals act as their own controls should be conducted to clarify any association between treatment with these medications and RS, controlling for confounding factors.
PMID: 39875750
ISSN: 1179-1934
CID: 5780812