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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

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

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

Stop and Think: A Case Study Illustrating the Implementation of Bright IDEAS-YA Being Delivered via Telehealth to a Young Adult Cancer Patient

Reese, Samantha; Bono, Madeline H; Díaz, Diana B; Donovan, Kristine A; Sahler, Olle Jane Z; Barnett, Marie E; Levonyan-Radloff, Kristine; Devine, Katie A
Bright IDEAS-Young Adults (Bright IDEAS-YA) is a problem-solving skills training intervention that has been adapted for young adults with cancer. Presently, a multisite randomized control trial is being conducted to determine Bright IDEAS-YA's efficacy in supporting a young adult population. This case study demonstrates the young adult adaptation of Bright IDEAS - Bright IDEAS-YA - being delivered to a young adult cancer patient via telehealth. Telehealth is a novel delivery method for Bright IDEAS and Bright IDEAS-YA that was established due to COVID-19 safety precautions. The patient, who reported challenges in several life domains, was taught how to apply the Bright IDEAS-YA framework over six telehealth sessions. After completing the Bright IDEAS-YA framework, the patient reported increased feelings of confidence in managing new stressors, which was corroborated through outcome measures delivered during and following intervention. This case illustrates how early psychosocial intervention following a cancer diagnosis, delivered via telehealth, can help patients develop and implement personal strategies to reduce stress levels.
PMCID:11403064
PMID: 38491206
ISSN: 1573-3572
CID: 5712312

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

Genomics yields biological and phenotypic insights into bipolar disorder

O'Connell, Kevin S; Koromina, Maria; van der Veen, Tracey; Boltz, Toni; David, Friederike S; Yang, Jessica Mei Kay; Lin, Keng-Han; Wang, Xin; Coleman, Jonathan R I; Mitchell, Brittany L; McGrouther, Caroline C; Rangan, Aaditya V; Lind, Penelope A; Koch, Elise; Harder, Arvid; Parker, Nadine; Bendl, Jaroslav; Adorjan, Kristina; Agerbo, Esben; Albani, Diego; Alemany, Silvia; Alliey-Rodriguez, Ney; Als, Thomas D; Andlauer, Till F M; Antoniou, Anastasia; Ask, Helga; Bass, Nicholas; Bauer, Michael; Beins, Eva C; Bigdeli, Tim B; Pedersen, Carsten Bøcker; Boks, Marco P; Børte, Sigrid; Bosch, Rosa; Brum, Murielle; Brumpton, Ben M; Brunkhorst-Kanaan, Nathalie; Budde, Monika; Bybjerg-Grauholm, Jonas; Byerley, William; Cabana-Domínguez, Judit; Cairns, Murray J; Carpiniello, Bernardo; Casas, Miquel; Cervantes, Pablo; Chatzinakos, Chris; Chen, Hsi-Chung; Clarence, Tereza; Clarke, Toni-Kim; Claus, Isabelle; Coombes, Brandon; Corfield, Elizabeth C; Cruceanu, Cristiana; Cuellar-Barboza, Alfredo; Czerski, Piotr M; Dafnas, Konstantinos; Dale, Anders M; Dalkner, Nina; Degenhardt, Franziska; DePaulo, J Raymond; Djurovic, Srdjan; Drange, Ole Kristian; Escott-Price, Valentina; Fanous, Ayman H; Fellendorf, Frederike T; Ferrier, I Nicol; Forty, Liz; Frank, Josef; Frei, Oleksandr; Freimer, Nelson B; Fullard, John F; Garnham, Julie; Gizer, Ian R; Gordon, Scott D; Gordon-Smith, Katherine; Greenwood, Tiffany A; Grove, Jakob; Guzman-Parra, José; Ha, Tae Hyon; Hahn, Tim; Haraldsson, Magnus; Hautzinger, Martin; Havdahl, Alexandra; Heilbronner, Urs; Hellgren, Dennis; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Holmans, Peter A; Huang, Ming-Chyi; Ikeda, Masashi; Jamain, Stéphane; Johnson, Jessica S; Jonsson, Lina; Kalman, Janos L; Kamatani, Yoichiro; Kennedy, James L; Kim, Euitae; Kim, Jaeyoung; Kittel-Schneider, Sarah; Knowles, James A; Kogevinas, Manolis; Kranz, Thorsten M; Krebs, Kristi; Kushner, Steven A; Lavebratt, Catharina; Lawrence, Jacob; Leber, Markus; Lee, Heon-Jeong; Liao, Calwing; Lucae, Susanne; Lundberg, Martin; MacIntyre, Donald J; Maier, Wolfgang; Maihofer, Adam X; Malaspina, Dolores; Manchia, Mirko; Maratou, Eirini; Martinsson, Lina; Mattheisen, Manuel; McGregor, Nathaniel W; McInnis, Melvin G; McKay, James D; Medeiros, Helena; Meyer-Lindenberg, Andreas; Millischer, Vincent; Morris, Derek W; Moutsatsou, Paraskevi; Mühleisen, Thomas W; O'Donovan, Claire; Olsen, Catherine M; Panagiotaropoulou, Georgia; Papiol, Sergi; Pardiñas, Antonio F; Park, Hye Youn; Perry, Amy; Pfennig, Andrea; Pisanu, Claudia; Potash, James B; Quested, Digby; Rapaport, Mark H; Regeer, Eline J; Rice, John P; Rivera, Margarita; Schulte, Eva C; Senner, Fanny; Shadrin, Alexey; Shilling, Paul D; Sigurdsson, Engilbert; Sindermann, Lisa; Sirignano, Lea; Siskind, Dan; Slaney, Claire; Sloofman, Laura G; Smeland, Olav B; Smith, Daniel J; Sobell, Janet L; Soler Artigas, Maria; Stein, Dan J; Stein, Frederike; Su, Mei-Hsin; Sung, Heejong; Świątkowska, Beata; Terao, Chikashi; Tesfaye, Markos; Tesli, Martin; Thorgeirsson, Thorgeir E; Thorp, Jackson G; Toma, Claudio; Tondo, Leonardo; Tooney, Paul A; Tsai, Shih-Jen; Tsermpini, Evangelia Eirini; Vawter, Marquis P; Vedder, Helmut; Vreeker, Annabel; Walters, James T R; Winsvold, Bendik S; Witt, Stephanie H; Won, Hong-Hee; Ye, Robert; Young, Allan H; Zandi, Peter P; Zillich, Lea; ,; Adolfsson, Rolf; Alda, Martin; Alfredsson, Lars; Backlund, Lena; Baune, Bernhard T; Bellivier, Frank; Bengesser, Susanne; Berrettini, Wade H; Biernacka, Joanna M; Boehnke, Michael; Børglum, Anders D; Breen, Gerome; Carr, Vaughan J; Catts, Stanley; Cichon, Sven; Corvin, Aiden; Craddock, Nicholas; Dannlowski, Udo; Dikeos, Dimitris; Etain, Bruno; Ferentinos, Panagiotis; Frye, Mark; Fullerton, Janice M; Gawlik, Micha; Gershon, Elliot S; Goes, Fernando S; Green, Melissa J; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Henskens, Frans A; Hjerling-Leffler, Jens; Hougaard, David M; Hveem, Kristian; Iwata, Nakao; Jones, Ian; Jones, Lisa A; Kahn, René S; Kelsoe, John R; Kircher, Tilo; Kirov, George; Kuo, Po-Hsiu; Landén, Mikael; Leboyer, Marion; Li, Qingqin S; Lissowska, Jolanta; Lochner, Christine; Loughland, Carmel; Luykx, Jurjen J; Martin, Nicholas G; Mathews, Carol A; Mayoral, Fermin; McElroy, Susan L; McIntosh, Andrew M; McMahon, Francis J; Medland, Sarah E; Melle, Ingrid; Milani, Lili; Mitchell, Philip B; Morken, Gunnar; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Myers, Richard M; Myung, Woojae; Neale, Benjamin M; Nievergelt, Caroline M; Nordentoft, Merete; Nöthen, Markus M; Nurnberger, John I; O'Donovan, Michael C; Oedegaard, Ketil J; Olsson, Tomas; Owen, Michael J; Paciga, Sara A; Pantelis, Christos; Pato, Carlos N; Pato, Michele T; Patrinos, George P; Pawlak, Joanna M; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Reininghaus, Eva Z; Ribasés, Marta; Rietschel, Marcella; Ripke, Stephan; Rouleau, Guy A; Roussos, Panos; Saito, Takeo; Schall, Ulrich; Schalling, Martin; Schofield, Peter R; Schulze, Thomas G; Scott, Laura J; Scott, Rodney J; Serretti, Alessandro; Smoller, Jordan W; Squassina, Alessio; Stahl, Eli A; Stefansson, Hreinn; Stefansson, Kari; Stordal, Eystein; Streit, Fabian; Sullivan, Patrick F; Turecki, Gustavo; Vaaler, Arne E; Vieta, Eduard; Vincent, John B; Waldman, Irwin D; Weickert, Cynthia S; Weickert, Thomas W; Werge, Thomas; Whiteman, David C; Zwart, John-Anker; Edenberg, Howard J; McQuillin, Andrew; Forstner, Andreas J; Mullins, Niamh; Di Florio, Arianna; Ophoff, Roel A; Andreassen, Ole A; ,
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
PMID: 39843750
ISSN: 1476-4687
CID: 5778012

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

Research Agenda in Childhood Impairing Emotional Outbursts: A Report of the AACAP Presidential Taskforce on Emotional Dysregulation

Althoff, Robert R; Singh, Manpreet K; Stringaris, Argyris; Constantino, John N; Amaya-Jackson, Lisa; Benton, Tami D; Bellonci, Christopher; Bostic, Jeff Q; Chua, Jaclyn Datar; Findling, Robert L; Galanter, Cathryn A; Gerson, Ruth S; McClellan, Jon M; Sorter, Michael T; Waxmonsky, James G; Carlson, Gabrielle A
OBJECTIVE/UNASSIGNED: The research agenda is presented here. METHOD/UNASSIGNED:The Taskforce specifically focused on aggressive behaviors and emotions associated with outbursts. The development of a research agenda took place over 2 years of examination of the current needs in the literature, with contributions from experts in the field. This work dovetailed with the efforts from the Congress on Pediatric Irritability and Dysregulation, which had been meeting since 2015 to advance research into the measurement, pathophysiology, and treatment of emotion regulation problems in youth. We concentrated on the central questions concerning the measurement of outbursts, key questions linking outbursts to other psychopathologies, and how behavior in outbursts is separable from typical behavior. RESULTS/UNASSIGNED:A description of the qualitative data gathering process is provided here, along with the following: recommendations in the research areas of measurement; pathophysiology; delineating outbursts from other psychopathologies; exploring the cultural, social, and interpersonal aspects of outbursts; understanding the prevention and treatment of outbursts; and exploring how outbursts manifest and are treated based on setting. Specific examples of research opportunities and future directions are provided. CONCLUSION/UNASSIGNED:A call is made to funding agencies to examine the spaces within their strategic plans that will allow for engagement in critical efforts to improve the lives of children and adolescents with severe emotional outbursts-some of the most impaired individuals presenting for care in child and adolescent psychiatry.
PMCID:11914913
PMID: 40109494
ISSN: 2949-7329
CID: 5813502

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