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Bipolar disorder is a leading contributor to the global burden of disease 1 . Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown 2 . 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 findings 3 , 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 disorder 4 , 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., Competing Interests: Competing interests: T.E.T., H. Stefansson and K.S. are employed by deCODE Genetics/Amgen. E.A.S. is an employee of Regeneron Genetics Center and owns stocks of Regeneron Pharmaceutical. K.-H.L. and X.W. are employed by 23andMe. Multiple additional authors work for pharmaceutical or biotechnology companies in a manner directly analogous to academic co-authors and collaborators. A.H.Y. has given paid lectures and served on advisory boards relating to drugs used in affective and related disorders for several companies (AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics and Sumitomo Dainippon Pharma), was Lead Investigator for the Embolden study (AstraZeneca), BCI Neuroplasticity study and Aripiprazole Mania study, and is an investigator for Janssen, Lundbeck, Livanova and Compass. J.I.N. is an investigator for Janssen. P.F.S. is on the advisory committee and a shareholder of Neumora Therapeutics. G.B. reports consultancy and speaker fees from Eli Lilly and Illumina, and grant funding from Eli Lilly. M. Landén has received speaker fees from Lundbeck. O.A.A. has served as a speaker for Janssen, Lundbeck and Sunovion, and as a consultant for Cortechs.ai. A.M.D. is a founder of and holds equity interest in CorTechs Labs and serves on its scientific advisory board; is a member of the scientific advisory board of Human Longevity and the Mohn Medical Imaging and Visualization Center; and has received research funding from General Electric Healthcare. E.V. has received grants and served as a consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Catalan Government (AGAUR and PERIS), the Spanish Ministry of Science, Innovation, and Universities (AES and CIBERSAM), the Seventh European Framework Programme and Horizon 2020 and the Stanley Medical Research Institute. S.K.-S. received author’s, speaker’s and consultant honoraria from Janssen, Medice Arzneimittel Pütter GmbH and Takeda outside of the current work. A. Serretti is or has been a consultant and/or speaker for: Abbott, AbbVie, Angelini, AstraZeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi and Servier. J.R.D. has served as an unpaid consultant to Myriad-Neuroscience (formerly Assurex Health) in 2017 and 2019, and owns stock in CVS Health. B.M.N. is a member of the scientific advisory board at Deep Genomics, and consultant for Camp4 Therapeutics, Takeda Pharmaceutical and Biogen. B.-C.L., J.-W.K., Y.K.L., J.H.K., M. J. Cheon and D.J.K. are employed by Genoplan. I.B.H. is the Co-Director of Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to Headspace. I.B.H. is also the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M (AUD) Australian Government-funded Project Synergy (2017–2020; a 3-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. M.J.O. and M.C.O. have received funding from Takeda Pharmaceuticals and Akrivia Health outside the scope of the current work. P. B. Mitchell. has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for lectures or advisory board membership. J.A.R.-Q. was on the speakers’ bureau and/or acted as consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the past 3 years; has also received travel awards (airplane tickets and hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubió, Takeda, Bial and Medice; and the Department of Psychiatry chaired by J.A.R.-Q. received unrestricted educational and research support from the following companies in the past 3 years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubió. All other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: This study aimed to identify phenotypic factors associated with genetic diagnoses in patients with neurodevelopmental disorders and generate a decision tree to assist clinicians in identifying patients most likely to receive a positive result on genetic testing., Methods: We retrospectively reviewed the charts of 316 patients evaluated in a neurodevelopmental clinic between 2014 and 2019. Patients were categorized based on genetic test results. Analyses were performed to identify variables that discriminate between patients with and without a genetic diagnosis., Results: Patients with a genetic diagnosis were more likely to be female and have a history of motor delay, hypotonia, congenital heart disease, and early intervention. Classification and regression tree analysis revealed that 75% of patients with motor delay had a genetic diagnosis. In patients without motor delay, hypotonia, age of walking, and age at initial evaluation were important indicators of a genetic diagnosis., Conclusion: Our findings suggest that motor delay and hypotonia are associated with genetic diagnoses in children with neurodevelopmental disorders. The decision tree highlights patient subsets at greater risk and suggests possible phenotypic screens. Future studies could develop validated decision trees based on phenotypic data to assist clinicians in stratifying patients for genetic testing., Competing Interests: Conflict of Interest Sunil Mehta acted as a paid consultant to Mirium Pharmaceuticals. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to develop and validate a short-form version of the AWE-S (AWE-SF) within psychedelic samples, to reduce participant burden while maintaining psychometric integrity. Across five studies, we first replicated the original six-factor structure of the AWE-S through exploratory and confirmatory factor analyses (Study 1), leading to the creation of the 12-item AWE-SF (Study 2-3). We then established the AWE-SF's initial and predictive validity by correlating it with relevant emotional, psychedelic, and well-being outcomes (Study 4-6). The AWE-SF demonstrated strong positive associations with positive emotions and was also linked to openness to experience. Moreover, the AWE-SF effectively predicted both mystical-type and challenging psychedelic experiences, as well as long-term well-being outcomes such as life satisfaction and psychological richness. In particular, the facets of connection and vastness were associated with positive emotional states and mystical-type experience, while accommodation and self-loss were associated with negative emotional states and challenging psychedelic experience. These findings suggest that the AWE-SF is a robust, reliable, and accessible tool for measuring awe experience., Competing Interests: Support for DBY through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Graziosi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Experimental cognitive tests are designed to measure particular cognitive domains, although evidence supporting test validity is often limited. The Consortium for Neuropsychiatric Phenomics test battery administered 23 experimental and traditional neuropsychological tests to a large sample of community volunteers ( n = 1,059) and patients with psychiatric diagnoses ( n = 137), providing a unique opportunity to examine convergent validity with factor analysis. Traditional tests included subtests from the Wechsler and Delis-Kaplan batteries, while experimental tests included the Attention Networks Test, Balloon Analogue Risk Task, Delay Discounting Task, Remember-Know, Reversal Learning Task, Scene Recognition, Spatial and Verbal Capacity and Manipulation Tasks, Stop-Signal Task, and Task Switching. Several experimental cognitive measures were insufficiently related to other tests and were excluded from factor analyses. In the remaining 18 tests, exploratory factor analysis and subsequent multigroup confirmatory factor analysis supported a three-factor structure broadly corresponding to domains of verbal/working memory, inhibitory control, and memory. In sum, several experimental measures of inhibitory control had weak relationships with all other tests, while the convergent validity of most tests of working memory and memory was supported., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Among older adults without cancer, living alone is associated with poor health outcomes. However, among older adults with non-small cell lung cancer (NSCLC) who live alone, data on function, cognition, and quality of life (QOL) during systemic treatment remain limited., Materials and Methods: We enrolled adults aged ≥65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or targeted therapy regimen with non-curative intent. Patients completed geriatric assessments including instrumental activities of daily living (IADL), Montreal Cognitive Assessment, and QOL pretreatment and at 1, 2, 4, and 6 months, or until treatment discontinuation, whichever occurred earlier. We categorized change in IADL, cognition, and QOL as stable/improved, declined with recovery, or declined without recovery using clinically meaningful definitions of change. We used multinomial logistic regression to compare change between patients who lived alone versus with others., Results: Among 149 patients, median age was 73; 21% lived alone. Pretreatment IADL, cognition, and QOL scores were similar between older adults who lived alone versus with others. During NSCLC treatment, older adults who lived alone had similar trajectories of function (52% functional decline vs 38%), cognition (43% cognitive decline vs 50%), and QOL (45% QOL decline vs 44%) compared with those who lived with others. In unadjusted analyses, patients who lived alone were more likely to develop functional decline with recovery (reference category: stable/improved function) than those who lived with others (relative risk ratio 4.07, 95% CI 1.14-14.6, p = 0.03). However, this association was not observed after adjusting for age, race, prior NSCLC treatment, current treatment group, and pretreatment geriatric assessment differences. There were no differences in cognitive or QOL trajectories in unadjusted or adjusted analyses., Discussion: Approximately half of older adults with advanced NSCLC who lived alone were able to maintain their function, cognition, and QOL during NSCLC treatment, which was similar to older adults who lived with others. Many older adults with advanced NSCLC who live alone can receive systemic treatment with individualized supportive care., Competing Interests: Declaration of Competing Interest SS reported conflicts of interest outside the submitted work (consultant/advisory to Oncohost). AIV reported conflicts of interest outside the submitted work (consultant/advisory to Merus and AstraZeneca). LCS has received research funding from AstraZeneca awarded directly to her institution. MLW reported conflicts of interest outside of the submitted work (royalties from UpToDate; immediate family member is an employee of Genentech with stock ownership). The remaining authors have no conflicts to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Depression is associated with poor outcomes in breast cancer survivors (BCSs), with higher prevalence among younger women. The Pathways to Wellness (PTW; ClinicalTrials.gov identifier: NCT03025139) randomized controlled trial (RCT) demonstrated beneficial effects of two behavioral interventions (survivorship education [SE] and mindful awareness practices [MAPs]) on depressive symptoms in younger BCS. We conducted an exploratory secondary analysis to identify moderators of intervention effects., Methods: Women diagnosed with stage 0 to III breast cancer at or before age 50 years who completed cancer treatment were randomly assigned to 6 weeks of SE (n = 81), MAPs (n = 85), or waitlist control (WLC; n = 81). Moderators assessed at baseline included psychological distress (depression and anxiety), intervention preference, preparedness for survivorship, and time since initial diagnosis. Linear regression models tested the modifying effects of each variable on postintervention depression in SE versus WLC and MAPs versus WLC., Results: Baseline levels of depression (β = -.03, P < .01) and anxiety (β = -.64, P = .02) moderated effects of SE on depressive symptoms, as did preparedness for survivorship (β = 3.17, P = .02). Participants randomly assigned to SE who had the highest levels of depression or anxiety and who felt least prepared for survivorship showed the largest reductions in depressive symptoms from preintervention to postintervention. Similar effects were not observed for MAPs. Intervention preference and time since diagnosis did not moderate intervention effects for either SE or MAPs., Conclusion: Our 6-week, group-based SE program may be most beneficial for women with higher levels of psychological distress and those who feel least prepared for cancer survivorship. By contrast, a 6-week mindfulness awareness practice intervention appears to benefit younger BCS regardless of pretreatment characteristics.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, CRTC3, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, DPH1, GSDMB, MED24 and THRA in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of BD polygenic risk scores across diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI)., Competing Interests: Competing interests OAA has served as a speaker for Janssen, Lundbeck, and Sunovion and as a consultant for Cortechs.ai. SKS has served as speaker for Janssen, Takeda and Medice Arzneimittel Puetter GmbH & CoKG. EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Abbvie, Adamed, Angelini, Biogen, Biohaven, Boehringer Ingelheim, Casen-Recordati, Celon, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo Smith-Kline, Idorsia, Janssen, Johnson & Johnson, Lundbeck, Newron, Novartis, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris. PBM has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for lectures, and Janssen (Australia) for advisory board membership. MOD and MJO have received grants from Akrivia Health and Takeda Pharmaceuticals for work unrelated to this project.

Mental health disparities between racial/ethnic minority groups and non-Latinx Whites in the United States persist despite significant efforts aimed at decreasing these disparities. Efforts to address mental health disparities have largely focused on individual (e.g., stigma, help-seeking, health behaviors) and structural (e.g., public policy, interventions, addressing poverty) level factors. In contrast, this paper considers how processes at the interactional level (i.e., interactions between patients and providers) are also an important contributor to racial/ethnic disparities in mental health. Specifically, social psychological research has demonstrated how biases, including stereotypes, prejudice, and discrimination, can affect patient-provider interactions and contribute to mental health disparities. This narrative review of empirical studies that examine interactional processes between patients and mental health providers identified eleven studies to be included. Concepts represented in the studies are summarized and additional frameworks that can help explain how disparities are maintained are proposed. Last of all, practical suggestions for mitigating provider bias during patient-provider interactions are provided based on the findings from the narrative review., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There are few studies of impacts of arts on recovery in schizphrenia, on audience mood and social connection. We developed a pilot evaluation of opera performances in a university setting on Elyn Saks' journey from psychosis, teaching law and falling in love, coupled with pre-opera workshop on approaches to resilience. Using surveys, primary outcomes were pre and post affect (PANAS-X positive, negative; visual "affect grid" touchscreen for affective valence and arousal) and social connectedness with secondary outcomes of increasing understanding, reducing stigma and willingness to socialize or serve persons with mental illness. Of 107 live and 117 online attendees, 64 completed pre, 24 post, and 22 both surveys. Respondent characteristics were similar for those with pre and pre and post surveys: average age mid 50's, half female, 10% sexual minority, half White/Caucasian, 13% Hispanic/Latino, 11% Black/African American and 20% Asian; of 22 with pre and post, 9 (41%) were providers. There were significant post-pre increases in positive affect (PANAS-X) and arousal (visual grid) and social connectedness (Cohen's d = 0.82 to 1.24, each p < .001); and willingness to socialize with someone with schizophrenia (d = 0.68, p = .011). In this pilot evaluation of opera in a university auditorium, despite small sample sizes, there were significant post-pre increases in audience positive affect and social connection, which could reflect selection (those with positive response completing surveys) or may suggest that arts events promote well-being and connection, issues for future larger studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants ( N  = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ms. Barber, Mr. Pitts, Mr. Stiede, and Dr. Compton declare that they have no conflicts of interest. Dr. Espil has received research support from the Foundation for OCD Research and honoraria from Springer Nature. Dr. Woods receives royalties from Guilford Press, Springer Press, and Oxford University Press and royalties for www.tichelper.com. Dr. Woods also receives speaking fees from the Tourette Association of America. Dr. Specht receives research support and speaking honoraria from the Tourette Association of America. Dr. Bennett receives royalties from UpToDate for an entry on child anxiety, and honoraria from the Tourette Association of America for CBIT training/talks and Lyra Health for speakers’ bureau. Dr. Walkup has served on advisory boards for the TLC Foundation for Body-Focused Repetitive Behaviors, Tourette Association of America, and the Anxiety and Depression Association of America. He has received speaking fees from the Tourette Association of America and AACAP. Dr. Walkup receives research funding from the Tourette Association of America and royalties from Oxford Press, Guilford Press, and Wolters Kluwer. Dr. Ricketts has received research funding from the National Institute of Mental Health (NIMH), Brain and Behavior Research Foundation, and the TLC Foundation for Body-Focused Repetitive Behaviors. She has received honoraria and research funding from the Tourette Association of America (TAA). She has received honoraria from the Centers for Disease Control and Prevention and Springer Nature. Dr. McGuire has received research support from the American Academy of Neurology, American Brain Foundation, American Psychological Foundation, Hilda and Preston Davis Foundation, Misophonia Research Fund, Tourette Association of America, and National Institute of Health. Dr. McGuire has received royalties from Elsevier and serves as a consultant for Signant Health, Syneos Health, and Luminopia. He has received editorial honoraria from Springer Nature and speakers’ bureau from the International OCD Foundation Pediatric Behavior Therapy Training Institute, and Tourette Association of America Scientific Advisory Board. Dr. Peterson reports receiving royalties from Oxford University Press for treatment manuals on tic disorders and receiving honoraria for CME presentations from the Tourette Association of America. Dr. Scahill has received research support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the US Department of Defense, and the Marcus Foundation. He has served as a consultant to Janssen Pharmaceuticals, Impel NeuroPharma and Cogstate. Dr. Scahill has received licensing fees from Roche, Yamo Pharmaceuticals, and Abbvie. He has received royalties from Guilford Press, Oxford University Press, and American Psychiatric Association Publishing. Dr. Wilhelm is a presenter for the Massachusetts General Hospital Psychiatry Academy in educational programs supported through independent medical education grants from pharmaceutical companies. She has received royalties from Guilford Publications, New Harbinger Publications, Springer, and Oxford University Press. Dr. Wilhelm has also received speaking honoraria from various academic institutions and foundations, including the International Obsessive Compulsive Disorder Foundation, the Tourette Association of America, and the Centers for Disease Control and Prevention. In addition, she received honoraria for her role on the Scientific Advisory Board for One-Mind (PsyberGuide), Koa Health, Inc., and Noom, Inc. Dr. Wilhelm has received research and salary support from Koa Health, Inc. Dr. Piacentini receives research support from NIMH, Patient-Centered Outcomes Research Institute (PCORI) and the TLC Foundation for BFRBs, advisor fees and equity from Lumate Health; publication royalties from Guilford Press, Oxford University Press, and Elsevier; and travel/speaking honoraria from the Tourette Association of America and International OCD Foundation.

Studies of health care access and use among historically resilient populations, while common, often field a limited sample size and rarely ask the groups most impacted by health inequities to weigh in. This is especially so for research and programs that focus on the American Indian and Alaska Native (AIAN) population. The present study addresses this gap by examining data from a cross-sectional survey of AIANs in Los Angeles County. To better interpret project findings and generate culturally relevant contexts, qualitative feedback was gathered at a community forum held in Spring 2018. Because recruitment of AIANs has historically been challenging, purposive sampling was employed to strategically identify a larger eligible pool. Among those who were eligible, 94% completed the survey (n = 496). AIANs who were enrolled in a tribe were 32% more likely to use the Indian Health Service (IHS), compared with those who were not enrolled (95% CI: 20.4%, 43.2%; p < .0001). In multivariable modeling, the strongest factors influencing IHS access and use were: tribal enrollment, preference for culturally-specific health care, proximity of the services to home or work, having Medicaid, and having less than a high school education. Feedback from the community forum indicated cost and trust (of a provider) were important considerations for most AIANs. Study findings reveal heterogeneous patterns of health care access and use in this population, suggesting a need to further improve the continuity, stability, and the image of AIANs' usual sources of care (e.g., IHS, community clinics)., (© 2023. W. Montague Cobb-NMA Health Institute.)

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a "musi-linguistic" continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech.

This article describes the development of a distance-delivered social skills training program for adults with Williams syndrome (SSTP-WS) through a community engaged approach. Throughout six phases of development, the research team received input from adults with Williams syndrome, caregivers, service providers, educators, and researchers on (a) the need for a training program and topics to be addressed (Phase 1), (b) an initial draft of the SSTP-WS (Phase 3), (c) the intervention pilot study (Phase 5), and (d) feedback to provide context for the results of the study (Phase 6). The development of the SSTP-WS resulted in an intervention aligned with the Williams syndrome community's values and needs that supports the unique cognitive and behavioral phenotypes and social characteristics of this low incidence disability population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6 , DALRD3 , CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder., Competing Interests: Chris German is employed by and hold stock or stock options in 23andMe, Inc. Erika L. Nurmi is on the Scientific Advisory Board for Myriad Genetics and Medical Advisory Board for Tourette Association of America and received Clinical trial funding from Emalex and Octapharma Pharmaceuticals. Jeremy Veenstra-VanderWeele has served on advisory boards or consulted with Roche, Novartis, and SynapDx; received research funding from Roche, Novartis, SynapDx, Seaside Therapeutics, Forest, Janssen, Acadia, Yamo, and MapLight; received stipends for editorial work from Wiley and Springer. Jens R. Wendland is a current employee and shareholder of Takeda Pharmaceuticals and a past employee and shareholder of F. Hoffmann-La Roche, Pfizer and Nestle Health Science. Cynthia M. Bulik reports: Pearson (author, royalty recipient).Peter Falkai reports no conflict of interest regarding this study and reports to have received financial support and Advisory Board: Richter, Recordati, Boehringer-Ingelheim, Otsuka, Janssen and Lundbeck. Hans J. Grabe has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care. Ian B. Hickie is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney, Australia. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. Professor Hickie has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca, Janssen Cilag) projects focused on the identification and better management of anxiety and depression. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd which aims to transform mental health services through the use of innovative technologies. Benjamin M. Neale is a member of the scientific advisory board at Deep Genomics and Neumora. Christopher Pittenger consults and/or receives research support from Biohaven Pharmaceuticals, Freedom Biosciences, Ceruvia Lifesciences, Transcend Therapeutics, UCB BioPharma, and F-Prime Capital Partners. He owns equity in Alco Therapeutics. These relationships are not related to the current work. Dan J. Stein has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. Eric A. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He was formerly a consultant for Brainsway and Biohaven Pharmaceuticals in the past 12 months. He owns stock less than $5000 in NView/Proem for distribution related to the YBOCS scales. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Ole A. Andreasson reports to be a consultant to Cortechs.ai, Precision Health AS, speakers honorarium from Otsuka, Lundbeck, Sunovion, Janssen. Anders D. Børglum has received speaker fee from Lundbeck. David Mataix-Cols receives royalties for contributing articles to UpToDate, Wolters Kluwer Health, and personal fees for editorial work from Elsevier, all unrelated to the current work. Murray B. Stein has in the past 3 years received consulting income from Acadia Pharmaceuticals, BigHealth, Biogen, Bionomics, Boehringer Ingelheim, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, Otsuka, PureTech Health, Sage Therapeutics, Sumitomo Pharma, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). Joel Gelernter is paid for editorial work by the journal Complex Psychiatry. Pino Alonso has received funding from Biohaven, Boston Scientific, Medtronic. All other authors report no conflicts of interest.

Background: Evidence-based practices (EBPs) improve housing and health for persons who have experienced homelessness with serious mental illness (PEH-SMI) but are challenging to implement. We tested a strategy to support pilot implementation of a 12-session housing skills training intervention for PEH-SMI, tailored from effective social skills training interventions. We aimed to optimize the implementation strategy and intervention prior to an implementation trial., Method: We provided training and technical assistance to nine providers to support pilot implementation of this intervention to six groups of PEH-SMI ( n  = 35) engaged in VA Greater Los Angeles' homeless services. We used scales and semi-structured interviews with 14 PEH-SMI and all interventionists to inform implementation strategy adaptations, identify factors that impacted implementation, and assess perceptions of the intervention. Attendance was tracked and we observed a random sample of each interventionist's groups to assess treatment fidelity., Results: Interventionists perceived the implementation strategy and the intervention favorably. However, interventionists often lacked physical space, staff, and resources (e.g., computers) to conduct the intervention. Interventionists found the content valuable for participants and a few suggested that group engagement should be a prerequisite for obtaining housing services. PEH-SMI were interested in the intervention's content and receptive to the group-based format. Participants attended a mean of 4 ± 3/12 groups; all groups observed had acceptable fidelity. Problems with intervention retention were described, suggesting challenges maintaining group participation when participants transitioned between VA homeless services., Conclusions: To support the implementation of an EBP for PEH-SMI in homeless programs, these data suggest the value of training/technical assistance and strategies that enhance program-level buy-in to address resource concerns. Intervention adaptations, e.g., using a drop-in, open group format, in community-based settings that are easily accessible to PEH-SMI, may also increase adoption. This project was registered as "Improving Housing Outcomes for Homeless Veterans" Trial registration NCT03646149, registered 8/24/2018., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Anxiety disorders often emerge in adolescence and are associated with risk aversion. Risk aversion conflicts with the typical adolescent approach-motivated phenotype and can interfere with learning and contribute to symptom maintenance., Methods: We investigated the neural and behavioral correlates of risk avoidance in a diverse sample of adolescents (N = 137; M Age  = 11.3; 34.3 % white, 22.1 % Latino, 20 % Asian, 14.3 % Black, 9.3 % Mixed Race) as they completed a task involving risky decision-making and response inhibition during fMRI. Voluntary cautious choice was compared to successful response inhibition to isolate the neural systems underlying the decision to avoid a risk and identify their relation to risk-taking and anxiety in adolescents., Results: Anxious adolescents self-reported more avoidance but demonstrated normative risk-taking on the laboratory task. Interestingly, they responded quickly during response inhibition but took longer to decide in the face of risk. All youth showed widespread recruitment of decision-making and salience network regions when deciding to avoid risk. The neural mechanisms driving avoidance differed based on anxiety such that left inferior frontal gyrus (IFG) activation was linked to risk avoidance in adolescents with low anxiety and risk-taking in anxious adolescents, while striatal connectivity was linked to risk avoidance in anxious adolescents and risk-taking in those with low anxiety., Limitations: This work is cross-sectional and therefore cannot speak to causality or directionality of effects., Conclusions: These results suggest that the neural mechanisms contributing to adolescent risk-taking may function to promote avoidance in anxious youth, increasing vulnerability to maladaptive avoidance and further anxiety development., Competing Interests: Declaration of competing interest Dr. Peris has grant funding from NIMH and PCORI. Dr. Galván has grant funding from NIMH and the FAST Consortium. Amanda E. Baker has no conflicts of interest to disclose. Namita Tanya Padgaonkar has no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The Pathways to Wellness randomized controlled trial found that 2 behavioral interventions, mindfulness awareness practices and survivorship education, reduced depressive symptoms in younger breast cancer survivors (BCSs) compared with wait-list control. This secondary analysis examines whether the interventions led to reduced loss of work productivity among younger BCSs and whether such reductions were mediated by reductions in depressive symptoms., Methods: The Work Productivity and Activity Impairment scale was used to measure work productivity loss at 4 assessment time points. Correlates of productivity loss at enrollment were examined using multivariable linear regression. Differences in change over time in productivity loss between each intervention group and control were assessed using linear mixed models. Reduced depressive symptoms were tested as a mediator of reduced productivity loss., Results: Of 247 trial participants, 199 were employed and included in the analyses. At enrollment, higher productivity loss was associated with chemotherapy receipt (P = .003), younger age (P = .021), more severe cognitive problems (P = .002), higher musculoskeletal pain severity (P = .002), more depressive symptoms (P = .016), and higher fatigue severity (P = .033). The mindfulness intervention led to significantly less productivity loss compared with control at all 3 postintervention assessment points (all P < .05), with about 54% of the effect mediated by reduction in depressive symptoms. Survivorship education was not associated with reduced loss of productivity., Conclusions: These findings suggest that addressing depressive symptoms through behavioral interventions, such as mindfulness, may mitigate impacts on work productivity in younger BCSs., Competing Interests: Author Disclosures Conflict of Interest Disclosures for this article can be found here., (Copyright © 2024. Published by Elsevier Inc.)

American Indian/Alaska Native (AI/AN) communities are disproportionately affected by the opioid epidemic. AI/AN emerging adults (ages 18-25) in urban areas are at particularly high risk, with the overdose death rate among urban-dwelling AI/AN people 1.4 times higher than rural-dwelling AI/AN people. Despite these challenges, there are no evidence-based culturally tailored prevention or intervention programs to address opioid, alcohol and other drug use among urban AI/AN emerging adults. This study focused on understanding AI/AN emerging adults' experiences with two culturally tailored programs addressing opioid, cannabis, and alcohol use as part of the randomized controlled trial for Traditions and Connections for Urban Native Americans (TACUNA) in order to enhance feasibility of this intervention. Using a convergent mixed methods design at 3-month follow-up, we collected satisfaction and experience ratings and written narratives (total n = 162; intervention n = 77; control n = 85) from a sample of urban-dwelling AI/AN emerging adults who participated in both programs. We analyzed data through simultaneous examination of qualitative and quantitative data. The quantitative ratings show that both programs were rated highly. The qualitative data contextualized these ratings, illustrating pathways through which specific components were perceived to cause desired or observed behavioral change in participants. Among the elements that mattered most to these participants were the convenience of the virtual format, having a comfortable and safe space to share personal stories, and learning new information about their social networks. Negative comments focused on workshop length and inconvenient scheduling. This is one of the first studies to explore participant satisfaction and experience with culturally tailored substance use programming among a historically marginalized and understudied population. It is important to consider the voices of urban-dwelling AI/AN people in program development because hidden factors, such as limited financial resources, limited time, and misalignment with cultural values may prevent existing programs from being feasible., (© 2023. The Author(s).)

Objective: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT)., Method: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40)., Results: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals., Conclusions: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision. To address these issues, we developed a combined cross-sectional study and randomized controlled trial, called the California Stress, Trauma, and Resilience Study (CalSTARS), to (a) characterize how ACEs influence multisystem biological functioning in adults with all levels of ACE burden and current perceived stress, using multiomics and other complementary approaches, and (b) test the efficacy of our new California Prec ision I ntervention for S tress and R e silience (PRECISE) in adults with elevated perceived stress levels who have experienced the full range of ACEs. The primary trial outcome is perceived stress, and the secondary outcomes span a variety of psychological, emotional, biological, and behavioral variables, as assessed using self-report measures, wearable technologies, and extensive biospecimens (i.e. DNA, saliva, blood, urine, & stool) that will be subjected to genomic, transcriptomic, proteomic, metabolomic, lipidomic, immunomic, and metagenomic/microbiome analysis. In this protocol paper, we describe the scientific gaps motivating this study as well as the sample, study design, procedures, measures, and planned analyses. Ultimately, our goal is to leverage the power of cutting-edge tools from psychology, multiomics, precision medicine, and translational bioinformatics to identify social, molecular, and immunological processes that can be targeted to reduce stress-related disease risk and enhance biopsychosocial resilience in individuals and communities worldwide.

Background: Population health management tools (PHMTs) embedded within electronic health records (EHR) could improve management of high-risk patients and reduce costs associated with potentially avoidable emergency department visits or hospitalizations. Adoption of PHMTs across the Veterans Health Administration (VA) has been variable and previous research suggests that understaffed primary care (PC) teams might not be using the tools., Methods: We conducted a retrospective content analysis of open-text responses (n = 1804) from the VA's 2018 national primary care personnel survey to, 1) identify system-level and individual-level factors associated with why clinicians are not using the tools, and 2) to document clinicians' recommendations to improve tool adoption., Results: We found three themes pertaining to low adoption and/or tool use: 1) IT burden and administrative tasks (e.g., manually mailing letters to patients), 2) staffing shortages (e.g., nurses covering multiple teams), and 3) no training or difficulty using the tools (e.g., not knowing how to access the tools or use the data). Frontline clinician recommendations included automating some tasks, reconfiguring team roles to shift administrative work away from providers and nurses, consolidating PHMTs into a centralized, easily accessible repository, and providing training., Conclusions: Healthcare system-level factors (staffing) and individual-level factors (lack of training) can limit adoption of PHMTs that could be useful for reducing costs and improving patient outcomes. Future research, including qualitative interviews with clinicians who use/don't use the tools, could help develop interventions to address barriers to adoption., Implications: Shifting more administrative tasks to clerical staff would free up clinician time for population health management but may not be possible for understaffed PC teams. Additionally, healthcare systems may be able to increase PHMT use by making them more easily accessible through the electronic health record and providing training in their use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Evidence-based health interventions are frequently translated into real-world settings where practical needs drive changes to intervention protocols. Due to logistical and resource constraints, these naturally arising adaptations are rarely assessed for comparative effectiveness using a randomized trial. Nevertheless, when observational data are available, it is still possible to identify beneficial adaptations using statistical methods that adjust for differences among intervention groups. As implementation continues and more data are collected and assessed, we also require analysis methods that ensure low statistical error rates as multiple comparisons are made over time. This paper describes how to create a statistical analysis plan for evaluating adaptations to an intervention during ongoing implementation. This can be done by combining methods commonly used in platform clinical trials with methods used for real-world data. We also demonstrate how to use simulations based on previous data to decide the frequency with which to conduct statistical analyses. The illustration uses data from large-scale implementation of a school-based resilience and skill-building preventive intervention to which several adaptations were made. The proposed statistical analysis plan for evaluating the school-based intervention has potential to improve population-level outcomes as implementation scales up further and additional adaptations are anticipated., (© 2023. Society for Prevention Research.)

Nationwide efforts to enhance services for adolescents experiencing commercial sexual exploitation (CSE) in the judicial system have led to the emergence of specialty courts, including human trafficking and girls' courts. Given that prior research has documented competing stances on the effectiveness of specialty courts for CSE-impacted populations, we conducted a systematic review of the literature to identify key characteristics of programming, profiles of adolescents served, and effectiveness of these courts. To identify relevant research and information, we systematically searched scholarly databases and information sources, conducted reference harvesting, and forwarded citation chaining. Articles presenting primary data with quantitative, qualitative, or mixed methodologies or programmatic descriptions of specialty courts serving adolescents at risk or with confirmed histories of CSE that were published after 2004 were included. We identified 39 articles on 21 specialty courts serving adolescents at risk or with confirmed histories of CSE, including seven specialty courts with evaluation or outcome data. Across specialty courts, adolescents benefited from an increase in linkage to specialized services, improved residential placement stability, and reduction in recidivism-measured by new criminal charges. Specialty court participation was also associated with improved educational outcomes and decreased instances of running away. A lack of empirical data, specifically of evaluation studies, emerged as a weakness in the literature. Still, findings support that specialty courts can be an integral judicial system response to CSE. Multidisciplinary collaboration can help target and respond to the multifaceted needs of adolescents, encourage healthy behaviors, and promote their overall wellness.

The population of persons of color (POC) are increasing in the United States. Unfortunately, POC are significantly impacted by serious mental illness; psychosis represents a mental health disparity among POC. Fortunately, first episode coordinated specialty care (CSC) is an effective treatment for individuals who are in the early phases of a psychotic disorder. This systematic review of the literature examined POC inclusion rates in randomized controlled trials (RCT) examining First Episode Psychosis (FEP) programs. Our review yielded seven articles that met inclusion criteria. Our findings were mixed-researchers conducting RCTs on FEP programs did an excellent job including African American participants suggesting that findings from RCTs on FEP programs may generalize to African American participants. Regarding Latines, they were broadly underrepresented in RCTs on FEP CSC. Based on the data, we cannot definitively conclude to what extent findings from RCTs on FEP CSC generalize to Latines although results from studies that included a reasonable number of Latines offer promising results. Asians were overrepresented in three of the seven studies included in this review; thus it seems that the findings from RCTs on FEP CSC generalize to the Asian population in the United States., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

Racial/ethnic minoritized (REM) youth represent a high-risk group for suicide, yet there are striking disparities in their use of mental health services (MHS) even after risk is identified in schools. Prior research suggests that school-based risk assessments and hospitalization encounters can be negatively experienced by REM youth and families, thus deterring likelihood of seeking follow-up care. The Safe Alternatives for Teens and Youth-Acute (SAFETY-A) is a brief, strengths-based, cognitive-behavioral family intervention demonstrated to increase linkage to MHS when implemented in emergency departments. With its focus on strengths and family engagement, SAFETY-A may cultivate a positive therapeutic encounter suited to addressing disparities in MHS by enhancing trust and family collaboration, if appropriately adapted for schools. Thirty-seven school district leaders and frontline school MHS providers from districts serving primarily socioeconomically disadvantaged REM communities participated in key informant interviews and focus groups. First, interviews were conducted to understand usual care processes for responding to students with suicidal thoughts and behaviors, and perspectives on the strengths and disadvantages of current practices. An as-is process analysis was used to describe current practices spanning risk assessment, crisis intervention, and follow-up. Second, focus groups were conducted to solicit perceptions of the fit of SAFETY-A for these school contexts. Thematic analysis of the interviews and focus groups was used to identify multilevel facilitators and barriers to SAFETY-A implementation, and potential tailoring variables for implementation strategies across school districts., Competing Interests: Declaration of Conflicting Interests: The Author(s) declare that there is no conflict of interest.

Purpose of Review: This review highlights recent findings regarding the prevalence, public health impact, clinical presentation, intervention access and conceptualization of fetal alcohol spectrum disorders (FASDs). Despite ongoing work in prevention and identification of this population, the rates of drinking during pregnancy have increased and significant gaps remain in diagnosis and intervention., Recent Findings: Prenatal alcohol exposure is the most common preventable cause of developmental disability in the world. Research has focused on improving diagnostic clarity, utilizing technology and neuroimaging to facilitate identification, engaging broader stakeholders (including self-advocates) to inform understanding and needs, and increasing access to effective interventions. There is an emerging focus on developmental trajectories and experiences in young and middle adulthood. Public policy advocacy has also made great strides in recent years., Summary: Increases in public awareness, greater concordance of diagnostic schema, leveraged use of novel technology, and the development of targeted interventions within a holistic, strengths-based conceptualization are important considerations for this population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Pleiotropy occurs when a genetic variant influences more than one trait. This is a key property of the genomic architecture of psychiatric disorders and has been observed for rare and common genomic variants. It is reasonable to hypothesize that the microscale genetic overlap (pleiotropy) across psychiatric conditions and cognitive traits may lead to similar overlaps at the macroscale brain level such as large-scale brain functional networks. We took advantage of brain connectivity, measured by resting-state functional MRI to measure the effects of pleiotropy on large-scale brain networks, a putative step from genes to behaviour. We processed nine resting-state functional MRI datasets including 32 726 individuals and computed connectome-wide profiles of seven neuropsychiatric copy-number-variants, five polygenic scores, neuroticism and fluid intelligence as well as four idiopathic psychiatric conditions. Nine out of 19 pairs of conditions and traits showed significant functional connectivity correlations (rFunctional connectivity), which could be explained by previously published levels of genomic (rGenetic) and transcriptomic (rTranscriptomic) correlations with moderate to high concordance: rGenetic-rFunctional connectivity = 0.71 [0.40-0.87] and rTranscriptomic-rFunctional connectivity = 0.83 [0.52; 0.94]. Extending this analysis to functional connectivity profiles associated with rare and common genetic risk showed that 30 out of 136 pairs of connectivity profiles were correlated above chance. These similarities between genetic risks and psychiatric disorders at the connectivity level were mainly driven by the overconnectivity of the thalamus and the somatomotor networks. Our findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, opening avenues to delineate general mechanisms-amenable to intervention-across psychiatric conditions and genetic risks., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Urban American Indian/Alaska Native (AI/AN) young adults and their families are often geographically or socially distant from tribal networks and traditional social support. Young adults can be especially vulnerable to cultural and social disconnection, so understanding how AI/AN family functioning can augment resilience and protect against risk is important. This research precedes a preventive substance use intervention study and explores urban Native family functioning, emphasizing the role of young adults by analyzing data from 13 focus groups with urban AI/AN young adults (n = 32), parents (n = 25), and health providers (n = 33). We found that young adults can and want to become agents of family resilience, playing active roles in minimizing risks and strengthening family functioning in both practical and traditional ways. Also, extended family and community networks played a vital role in shaping family dynamics to support resilience. These resilience pathways suggest potential targets for intervention., (© 2022. W. Montague Cobb-NMA Health Institute.)

Background: We examined whether digital phenotyping of spontaneous speech, such as the use of specific word categories during speech samples, was associated with depressive symptoms in youth who were at familial and clinical risk for mood disorders., Methods: Participants (ages 13-19) had active mood symptoms, mood instability, and at least one parent with bipolar or major depressive disorder. During a randomized trial of family-focused therapy, participants were instructed to make weekly calls to a central voice server and leave speech samples in response to automated prompts. We coded youths' speech samples with the Linguistic Inquiry and Word Count system and used machine learning to identify the combination of speech features that were most closely associated with the course of depressive symptoms over 18 weeks., Results: A total of 253 speech samples were collected from 44 adolescents (mean age = 15.8 years; SD = 1.6) over 18 weeks. Speech containing affective processes, social processes, drives toward risk or reward, nonfluencies, and time orientation words were correlated with depressive symptoms at concurrent time periods (ps < 0.01). Machine learning analyses revealed that affective processes, nonfluencies, drives and risk words combined to most strongly predict changes in depressive symptoms over 18 weeks of treatment., Limitations: Study results were limited by the small sample and the exclusion of paralinguistic or contextual variables in analyzing speech samples., Conclusions: In youth at high risk for mood disorders, knowledge of speech patterns may inform prognoses during outpatient psychosocial treatment., Competing Interests: Conflict of interest Dr. Weintraub reports research support from NIMH K23MH124015, the American Psychological Foundation, and the Friends of the UCLA Semel Institute. Dr. Arevian is CEO of Chorus Innovations and is supported by the California State Center of Excellence for Behavioral Health SB 852. He has a financial interest in Insight Health Systems, Inc. and Arevian Technologies Inc. Dr. Miklowitz receives research support from the National Institute for Mental Health (NIMH), the Danny Alberts Foundation, the Attias Family Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, AIM for Mental Health, Jewish Community Foundation of Los Angeles, and the Max Gray Fund; and book royalties from Guilford Press and John Wiley and Sons. The other authors have no declarations of interest., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Tamoxifen is a common treatment for estrogen receptor-positive breast cancer. While tamoxifen treatment is generally accepted as safe, there are concerns about adverse effects on cognition., Methods: We used a mouse model of chronic tamoxifen exposure to examine the effects of tamoxifen on the brain. Female C57/BL6 mice were exposed to tamoxifen or vehicle control for six weeks; brains of 15 mice were analyzed for tamoxifen levels and transcriptomic changes, and an additional 32 mice were analyzed through a battery of behavioral tests., Results: Tamoxifen and its metabolite 4-OH-tamoxifen were found at higher levels in the brain than in the plasma, demonstrating the facile entry of tamoxifen into the CNS. Behaviorally, tamoxifen-exposed mice showed no impairment in assays related to general health, exploration, motor function, sensorimotor gating, and spatial learning. Tamoxifen-treated mice showed a significantly increased freezing response in a fear conditioning paradigm, but no effects on anxiety measures in the absence of stressors. RNA sequencing analysis of whole hippocampi showed tamoxifen-induced reductions in gene pathways related to microtubule function, synapse regulation, and neurogenesis., Discussion: These findings of the effects of tamoxifen exposure on fear conditioning and on gene expression related to neuronal connectivity suggest that there may be CNS side effects of this common breast cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Galvano, Pandit, Sepulveda, Ng, Becher, Mandelblatt, Van Dyk and Rebeck.)

Objective: /Background: The goal of the present study was to assess the prevalence and incidence of insomnia in the United States during the COVID-19 pandemic, and whether, among those that contracted COVID-19, insomnia predicted worse outcomes (e.g., symptoms of greater frequency, duration, or severity)., Methods: A nationwide sample of 2980 adults living in the United States were surveyed online at two points during the COVID-19 pandemic (T1 = April-June 2020; T2 = January-March 2021). Insomnia symptoms were assessed at both time points using the Insomnia Severity Index (ISI). The T2 survey also asked questions regarding COVID-19 testing and symptoms., Results: The prevalence of insomnia (defined as ISI ≥15) was 15% at T1 and 13% at T2. The incidence rate of insomnia (i.e., new cases from T1 to T2) was 5.6%. Participants with insomnia were not more likely to contract COVID-19 relative to those participants without insomnia. Among those participants in our sample that contracted the virus during the study interval (n = 149), there were no significant group differences in COVID-19 symptom outcomes, with one exception, participants with insomnia were more likely to report a longer symptom duration (insomnia = 24.8 sick days, no insomnia = 16.1 sick days)., Conclusions: The present study suggests the prevalence of insomnia in the U.S. population remained high during the COVID-19 pandemic. The data also support that insomnia may be related to experiencing more chronic COVID-19 symptoms. These findings have more general implications for the role of sleep and insomnia on immune functioning., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Hallucinations and delusions present with psychosis are debilitating non-motor symptoms of Parkinson's disease, with a prevalence of up to 50-70% at some point during the course of the disease. Often patients and caregivers do not report the presence of hallucinations or delusions unless specifically questioned. A panel of experts in neurology and geriatric psychiatry convened to develop a simple screening tool and guidance on diagnosis and treatment of Parkinson's disease psychosis (PDP)., Methods: The working group reviewed literature for existing PDP guidelines on diagnosis and management and identified gaps in recommendations. The group discussed and developed a screening tool and treatment guidance that addressed the gaps in existing methodology based on their clinical experience., Results: The proposed screening tool consists of two parts: (1) a brief pre-visit screening portion to be completed by the patient and caregiver, and (2) a clinician portion to be completed via clinical interview of the patient and caregiver. If psychotic symptoms are present, an appropriate treatment plan is developed for PDP based on evaluation., Conclusions: This simple screening tool and treatment guidance offers a practical clinical approach for clinicians in the diagnosis and management of PDP., (© 2022. The Author(s).)

Post-acute sequelae of SARS-CoV-2 (PASC) is defined as persistent symptoms after apparent recovery from acute COVID-19 infection, also known as COVID-19 long-haul. We performed a retrospective review of electronic health records (EHR) from the University of California COvid Research Data Set (UC CORDS), a de-identified EHR of PCR-confirmed SARS-CoV-2-positive patients in California. The purposes were to (1) describe the prevalence of PASC, (2) describe COVID-19 symptoms and symptom clusters, and (3) identify risk factors for PASC. Data were subjected to non-negative matrix factorization to identify symptom clusters, and a predictive model of PASC was developed. PASC prevalence was 11% (277/2,153), and of these patients, 66% (183/277) were considered asymptomatic at days 0-30. Five PASC symptom clusters emerged and specific symptoms at days 0-30 were associated with PASC. Women were more likely than men to develop PASC, with all age groups and ethnicities represented. PASC is a public health priority.