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Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies

Uher, Rudolf; Pavlova, Barbara; Radua, Joaquim; Provenzani, Umberto; Najafi, Sara; Fortea, Lydia; Ortuño, Maria; Nazarova, Anna; Perroud, Nader; Palaniyappan, Lena; Domschke, Katharina; Cortese, Samuele; Arnold, Paul D; Austin, Jehannine C; Vanyukov, Michael M; Weissman, Myrna M; Young, Allan H; Hillegers, Manon H J; Danese, Andrea; Nordentoft, Merete; Murray, Robin M; Fusar-Poli, Paolo
The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.
PMCID:10503921
PMID: 37713573
ISSN: 1723-8617
CID: 5593242

National trends in depression and suicide attempts and COVID-19 pandemic-related factors, 1998-2021: A nationwide study in South Korea

Kang, Jiseung; Park, Jaeyu; Lee, Hojae; Lee, Myeongcheol; Kim, Sunyoung; Koyanagi, Ai; Smith, Lee; Kim, Min Seo; Rahmati, Masoud; Fond, Guillaume; Boyer, Laurent; López Sánchez, Guillermo F; Elena, Dragioti; Cortese, Samuele; Kim, Tae; Yon, Dong Keon
BACKGROUND:Despite the significant psychiatric effects of the COVID-19 pandemic, there's limited data on the prevalence and risk factors of depression and suicide attempts among South Korean adults. METHODS:A nationwide cross-sectional study using the Korea National Health and Nutrition Examination Survey (KNHANES) data from 1998 to 2021 was conducted. Changes in prevalence and risk factors for depression and suicide attempts were assessed using weighted odds ratios or weighted beta coefficients. RESULTS:During the observation period (1998-2021), the prevalence of depression increased in the overall population; however, no significant surge was found regarding the COVID-19 pandemic, from 2.78% (95% CI, 2.41-3.15) in 1998-2005-4.96% (4.32-5.61) in 2020 and 5.06% (4.43-5.69) in 2021. However, immediately after the onset of the pandemic, younger ages, male sex, urban residence, higher education, and high economic status became significant vulnerable factors compared to pre-pandemic periods. The prevalence of suicide attempts remained stable, and there was no notable surge specifically related to the COVID-19 pandemic, from 0.23% (95% CI, 0.18-0.28) in 1998-2005-0.45% (0.25-0.66) in 2020 and 0.42% (0.24-0.60) in 2021. Furthermore, no distinct vulnerable factors associated with suicide attempts have been identified. CONCLUSION/CONCLUSIONS:Through this nationwide serial cross-sectional survey study, we emphasized the need for understanding the differential impacts of global crises, such as COVID-19, across varied population subgroups, thereby highlighting the importance of specific and targeted mental health support strategies.
PMID: 37633158
ISSN: 1876-2026
CID: 5598952

Are Young Adult Survivors of Pediatric Cancer Being Overlooked? Cognitive Testing Results and Referrals in Child, Adolescent, and Young Adult Survivors

Pereira, Lila; Bono, Madeline H; Braniecki, Suzanne; Giblin, Tara; Lawton, Brittany
Treatment gaps in meeting the neuropsychological needs of young adult (YA) cancer survivors can be attributed to several clinical and systemic reasons. Access to neurocognitive care can be increased through the effective integration of neuropsychological monitoring and intervention in survivorship care. In this brief report, we aim to compare the efficacy of a brief neuropsychological screener (DIVERGT) in meeting the assessment and referral needs of pediatric and YA cancer survivors (n = 40) as part of a wellness and survivorship clinic. Participants (n = 40) were patients who presented to a pediatric oncology survivorship clinic over the span of 15 months.
PMID: 36856489
ISSN: 2156-535x
CID: 5712302

Variation in sleep profiles in children with ADHD and associated clinical characteristics

Sciberras, Emma; Hiscock, Harriet; Cortese, Samuele; Becker, Stephen P; Fernando, Julian W; Mulraney, Melissa
BACKGROUND:Sleep difficulties are common in children with attention-deficit/hyperactivity disorder (ADHD). However, sleep problems are multifaceted and little is known about the variation in sleep difficulties across children with ADHD. We examined the profiles of sleep difficulties in children with ADHD and associated clinical factors (e.g. co-occurring mental health conditions, stimulant use and parent mental health). METHODS:Data from two harmonised studies of children with ADHD (total: N = 392, ages 5-13 years) were used. Parents completed measures of children's sleep, co-occurring mental health conditions and their own mental health. Both parents and teachers completed measures of child ADHD symptoms and emotional and conduct symptoms. Latent profile analysis was used to identify sleep profiles, and multinomial logistic regression assessed clinical correlates of the groups. RESULTS:Five sleep profiles were identified: (a) insomnia/delayed sleep phase (36%), (b) generalised sleep difficulties at sleep onset and overnight (25%), (c) high anxious/bedtime resistance difficulties (11%), (d) overnight sleep difficulties including obstructive sleep apnoea and parasomnias (5%) and (e) no sleep difficulties (22%). Compared with the group without sleep difficulties, the generalised, anxious/bedtime resistance and insomnia/delayed sleep phase sleep had greater parent-reported emotional and conduct symptoms, co-occurring anxiety and increased parent mental health difficulties. The generalised and anxious/bedtime resistance groups also had greater parent-reported ADHD symptoms, with the anxious/bedtime resistance sleep group also having more frequent co-occurring depression and teacher-reported emotional symptoms. CONCLUSIONS:The sleep difficulties experienced by children with ADHD are varied. Supports to help children with ADHD need to consider the particular profiles of sleep difficulties experienced and broader clinical characteristics. Tailored intervention approaches are likely needed (including a need to address parent mental health).
PMID: 37272196
ISSN: 1469-7610
CID: 5593972

Importance of accurate and accessible recording of healthcare contacts in mental health [Comment]

Jack, Ruth H; Coupland, Carol A C; Joseph, Rebecca M; Hollis, Chris; Morriss, Richard; Knaggs, Roger David; Cipriani, Andrea; Cortese, Samuele; Hippisley-Cox, Julia
PMID: 37697323
ISSN: 1741-7015
CID: 5593932

Remote Recruitment Strategy and Structured E-Parenting Support (STEPS) App: Feasibility and Usability Study

Kostyrka-Allchorne, Katarzyna; Chu, Petrina; Ballard, Claire; Lean, Nancy; French, Blandine; Hedstrom, Ellen; Byford, Sarah; Cortese, Samuele; Daley, David; Downs, Johnny; Glazebrook, Cristine; Goldsmith, Kimberley; Hall, Charlotte L; Kovshoff, Hanna; Kreppner, Jana; Sayal, Kapil; Shearer, James; Simonoff, Emily; Thompson, Margaret; Sonuga-Barke, Edmund J S
BACKGROUND:The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants' recruitment and the app's usability. OBJECTIVE:This study aimed to adapt a digital routine clinical monitoring system, myHealthE, for research purposes to facilitate waitlist recruitment; test using remote methods to screen and identify participants quickly and systematically; pilot the acceptability of the recruitment and assessment protocol; and explore the usability of STEPS. METHODS:myHealthE was adapted to screen patients' data. Parents' and clinicians' feedback on myHealthE was collected, and information governance reviews were conducted in clinical services planning to host the RCT. Potential participants for the observational feasibility study were identified from new referrals using myHealthE and non-myHealthE methods. Descriptive statistics were used to summarize the demographic and outcome variables. We estimated whether the recruitment rate would meet the planned RCT sample size requirement (n=352). In addition to the feasibility study participants, another group of parents was recruited to assess the STEPS usability. They completed the adapted System Usability Scale and responded to open-ended questions about the app, which were coded using the Enlight quality construct template. RESULTS:Overall, 124 potential participants were identified as eligible: 121 (97.6%) via myHealthE and 3 (2.4%) via non-myHealthE methods. In total, 107 parents were contacted, and 48 (44.9%) consented and were asked if, hypothetically, they would be willing to participate in the OPTIMA RCT. Of the 28 feasibility study participants who provided demographic data, 21 (75%) identified as White. Their children had an average age of 8.4 (SD 1.7) years and 65% (31/48) were male. During the primary recruitment period (June to July 2021) when 45 participants had consented, 38 (84%) participants agreed hypothetically to take part in the RCT (rate of 19/mo, 95% CI 13.5-26.1), meeting the stop-go criterion of 18 participants per month to proceed with the RCT. All parents were satisfied or very satisfied with the study procedures. Parents (n=12) recruited to assess STEPS' usability described it as easy to navigate and use and as having an attractive combination of colors and visual design. They described the content as useful, pitched at the right level, and sensitively presented. Suggested improvements included adding captions to videos or making the recorded reflections editable. CONCLUSIONS:Remote recruitment and study procedures for testing a parenting intervention app are feasible and acceptable for parents. The parents felt that STEPS was a useful and easy-to-use digital parenting support tool. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:RR2-10.1186/s40814-021-00959-0.
PMCID:10520770
PMID: 37695667
ISSN: 2561-6722
CID: 5593722

Implementation of a gene therapy education initiative by the ASGCT and Muhimbili University of Health and Allied Sciences [Letter]

Cornetta, Kenneth; Kay, Samantha; Urio, Florence; Minja, Irene Kida; Mbugi, Erasto; Mgaya, Josephine; Mselle, Teddy; Nkya, Siana; Alimohamed, Mohamed Zahir; Ndaki, Kinuma; Bonamino, Martín; Koya, Richard C; Shah, Lesha D; Mahlangu, Johnny; Drago, Daniela; Rangarajan, Savita; Jayandharan, Giridhara Rao
There has been rapid growth in gene therapy development with an expanding list of approved clinical products. Several therapies are particularly relevant to patients in low- and middle-income countries. Moreover, investing in research and manufacturing presents an opportunity for economic development. To increase awareness of gene therapy, the American Society of Gene and Cell Therapy partnered with the Muhimbili University of Health and Allied Sciences, Tanzania, to create a certificate-bearing course. The goal was to provide faculty teaching in graduate and medical schools with the tools needed to add gene therapy to the university curriculum. The first virtual course was held in October of 2022, and 45 individuals from 9 countries in Africa completed the training. The content was new to approximately two-thirds of participants, with the remaining third indicating that the course increased their knowledge base. The program was well received and will be adapted for other under-resourced regions.
PMCID:10492022
PMID: 37595584
ISSN: 1525-0024
CID: 5598452

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial

Raison, Charles L; Sanacora, Gerard; Woolley, Joshua; Heinzerling, Keith; Dunlop, Boadie W; Brown, Randall T; Kakar, Rishi; Hassman, Michael; Trivedi, Rupal P; Robison, Reid; Gukasyan, Natalie; Nayak, Sandeep M; Hu, Xiaojue; O'Donnell, Kelley C; Kelmendi, Benjamin; Sloshower, Jordan; Penn, Andrew D; Bradley, Ellen; Kelly, Daniel F; Mletzko, Tanja; Nicholas, Christopher R; Hutson, Paul R; Tarpley, Gary; Utzinger, Malynn; Lenoch, Kelsey; Warchol, Kasia; Gapasin, Theraysa; Davis, Mike C; Nelson-Douthit, Courtney; Wilson, Steffanie; Brown, Carrie; Linton, William; Ross, Stephen; Griffiths, Roland R
IMPORTANCE:Psilocybin shows promise as a treatment for major depressive disorder (MDD). OBJECTIVE:To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. DESIGN, SETTING, AND PARTICIPANTS:In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. INTERVENTIONS:Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. MAIN OUTCOMES AND MEASURES:The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. RESULTS:A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. CONCLUSIONS AND RELEVANCE:Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03866174.
PMID: 37651119
ISSN: 1538-3598
CID: 5606332

Outcomes of People of Color in an Efficacy Trial of Cognitive-Behavioral Treatments for Anxiety, Depression, and Related Disorders: Preliminary Evidence

Cardona, Nicole D; Ametaj, Amantia A; Cassiello-Robbins, Clair; Tirpak, Julianne Wilner; Olesnycky, Olenka; Sauer-Zavala, Shannon; Farchione, Todd J; Barlow, David H
Although evidence-based psychological treatments such as cognitive behavioral therapy (CBT) have strong empirical support for reducing anxiety and depression symptoms, CBT outcome research often does not report race and ethnicity variables, or assess how well CBT works for people from historically excluded racial and ethnic groups. This study presents post hoc analyses comparing treatment retention and symptom outcomes for participants of color ( n = 43) and White participants ( n = 136) from a randomized controlled efficacy trial of CBT. χ 2 tests and one-way ANCOVA showed no observable differences between the two samples on attrition or on clinician-rated measures of anxiety and depression at posttreatment and follow-up. Moderate to large within-group effect sizes on anxiety and depression were found for Black, Latinx, and Asian American participants at almost all time points. These preliminary findings suggest that CBT for anxiety and comorbid depression may be efficacious for Black, Asian American, and Latinx individuals.
PMCID:10524474
PMID: 37432031
ISSN: 1539-736x
CID: 5807112

Sleep parameters and problems in adolescents with and without ADHD: A systematic review and meta-analysis

Marten, Finja; Keuppens, Lena; Baeyens, Dieter; Boyer, Bianca E; Danckaerts, Marina; Cortese, Samuele; Van der Oord, Saskia
BACKGROUND/UNASSIGNED:Adolescence is characterized by an increase in the rate of sleep problems, which might be even more pronounced in adolescents with ADHD. This systematic review with meta-analysis aimed to compare sleep in adolescents with and without ADHD, including sleep parameters, both subjectively and objectively measured, sleep problems and sleep hygiene. METHODS/UNASSIGNED:Medline, CINAHL, PsycINFO, EMBASE, ERIC, Web of Science, and PubMed databases were searched for studies with case-control designs (published between 1980 and 2022) directly comparing sleep in adolescents (12-25 years) with ADHD to typically developing controls. Standardized mean differences were calculated and a random-effects model was implemented using RevMan. RESULTS/UNASSIGNED: = 3) in any parameter. Differences in sleep hygiene could not be examined due to a limited number of studies. CONCLUSIONS/UNASSIGNED:Adolescents with ADHD report significantly worsened subjectively sleep parameters and more sleep problems compared to controls. These findings are still preliminary as a limited number of studies was identified. Nevertheless, it is advised to routinely include sleep assessment in the ADHD diagnostic process. More research is needed with a focus on objective measurement and sleep hygiene in ADHD.
PMCID:10501691
PMID: 37720581
ISSN: 2692-9384
CID: 5735222