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The increasing cultural diversity in the United States means more college students identify with racial and ethnic minority backgrounds and may experience acculturative stress. Emerging research has found an association between acculturative stress and maladaptive eating. However, these studies rarely consider other theoretical factors or confounders, and individual differences. Thus, the unique contribution of acculturative stress and the generalizability of previous findings remain unclear.ObjectiveThis cross-sectional study investigated the role of acculturative stress and self-construal (i.e., how individuals define themselves in relation to others in social environments) in maladaptive eating among female college students.MethodParticipants were 446 female young adults (Mage = 20.38, SD = 1.75; MBMI = 23.42, SD = 4.62) who completed online questionnaires.ResultsStructural equation modeling results showed that acculturative stress was related to higher disinhibited eating even when accounting for traditional theoretical risk factors (i.e., body dissatisfaction, perceived sociocultural pressures on body image, and general stress) and potential confounders (i.e., age, BMI, SES, ethnic backgrounds, and birthplace). Furthermore, independent self-construal (i.e., when individuals see themselves as autonomous, prioritizing personal goals and uniqueness over social relationships) moderated this association. When independent self-construal was higher, the magnitude of the regression coefficient between acculturative stress and disinhibited eating was smaller.DiscussionGiven the increasing diversity within U.S. higher education, eating behavior theories should consider integrating acculturative stress to improve inclusiveness. College psychological services should tailor prevention and treatment strategies for maladaptive eating to address acculturative stress, while also promoting an environment that supports healthy, independent self-construal.

BACKGROUND: 2022 survey data showed 29% of Veterans utilized Veterans Affairs (VA) paid health care at a non-VA facility, 6% higher than in 2021. Despite an increase in the number of Veterans accessing care in the community via the MISSION Act Community Care Program (CCP), there is limited information on the quality of mental health care delivered to Veterans in these settings. Further, Veterans report barriers to quality care, including poor communication between CCP and VA providers, which can result in negative patient outcomes. We aimed to evaluate the feasibility and acceptability of using electronic screening, eScreening, as part of a process involving remote symptom screening, symptom monitoring, and clinically driven communication from VA to CCP providers, for Veterans accessing mental health treatment in CCP settings. METHODS: Veterans (n = 150) diagnosed with major depressive disorder, an anxiety disorder, post-traumatic stress disorder, and/or an adjustment disorder referred to mental health care in CCP between August-November 2021 were eligible to participate. Veterans received an eScreening link to complete an initial web-based assessment and three follow-up assessments spaced 4-6 weeks apart over the course of their treatment. Quantitative assessment data was largely characterized using descriptive statistics and included patient-reported outcome (PRO) measures (PTSD and depression), health-related quality of life/functioning, community care information (e.g., number of sessions attended), and satisfaction with the eScreening technology. Qualitative interview data was also collected from participating Veterans and CCP providers to better understand experiences with eScreening. RESULTS: Findings support the feasibility and acceptability of using eScreening to administer and monitor PROs for Veterans accessing mental health treatment in CCP. Of the Veterans who provided eScreening satisfaction ratings (Ns = 45-55), 89% had no technical difficulties; 78% felt comfortable entering personal information; and 83% were neutral or positive about ease of use. Focus group interviews revealed strong support from Veterans, who stated the software was easy to use; they felt comfortable completing PRO measures; and they appreciated having their symptoms monitored. Similarly, providers indicated eScreening had a positive impact on communication, collaboration of care, and transparency. CONCLUSIONS: Technologies like eScreening represent a promising tool to support the mental health care Veterans receive when they access CCP.

Empathy plays a crucial role in promoting older adults' interpersonal experiences, but it remains unclear how these benefits of empathy occur. To address this gap, we examined associations between empathy and how older adults behave and express emotions during their daily interpersonal encounters. Participants included 268 adults aged 65+ (46% men, n = 124) from the Daily Experiences and Well-being Study. They reported background characteristics and empathy in baseline interviews and indicated interpersonal encounters every 3 hours across 5 to 6 days. Participants wore electronically activated recorders (EAR), an app that captured 30-second snippets of ambient sounds every 7 minutes. Verbatim transcripts were coded for positive and negative social behaviors (e.g., praise, complain) and text was analyzed via Linguistic Inquiry and Word Count (LIWC) software for verbal expressions of positive and negative emotions (e.g., happy, hope, hate, hurt). Multilevel models showed that greater empathy was associated with greater variety in positive social behaviors throughout the day. More empathic older adults expressed more positive emotions while engaging in positive behaviors and less negative emotions when engaging in negative behaviors. This study innovatively draws on naturalistic data to delineate how more empathic older adults may have more positive and less negative social experiences than their less empathic counterparts. Findings may inform interventions that can incorporate empathy training to target those at higher risk of poor interpersonal experiences and outcomes (e.g., social isolation).

Functional analysis of non-coding variants associated with congenital disorders remains challenging due to the lack of efficient in vivo models. Here we introduce dual-enSERT, a robust Cas9-based two-color fluorescent reporter system which enables rapid, quantitative comparison of enhancer allele activities in live mice in less than two weeks. We use this technology to examine and measure the gain- and loss-of-function effects of enhancer variants previously linked to limb polydactyly, autism spectrum disorder, and craniofacial malformation. By combining dual-enSERT with single-cell transcriptomics, we characterise gene expression in cells where the enhancer is normally and ectopically active, revealing candidate pathways that may lead to enhancer misregulation. Finally, we demonstrate the widespread utility of dual-enSERT by testing the effects of fifteen previously uncharacterised rare and common non-coding variants linked to neurodevelopmental disorders. In doing so we identify variants that reproducibly alter the in vivo activity of OTX2 and MIR9-2 brain enhancers, implicating them in autism. Dual-enSERT thus allows researchers to go from identifying candidate enhancer variants to analysis of comparative enhancer activity in live embryos in under two weeks.

This study investigates baseline differences in couples enrolled in the "It Takes Two" HIV prevention intervention for transgender women and their partners, comparing in-person participation pre-COVID-19 and digital participation during the pandemic. Among 52 couples (40% in-person, 60% digital), bivariate analyses revealed that in-person participants were more likely to be African American, have cisgender male partners, report higher unemployment, incarceration histories, greater relationship stigma, and lower relationship quality. The findings highlight the limitations of digital modalities in engaging transgender women of color and those with structural vulnerabilities. The study emphasizes that reliance on digital methods in HIV research jeopardizes the inclusion of those lacking technological access and literacy, especially communities disproportionately impacted by HIV. Researchers must incorporate hybrid or in-person options and engage communities to ensure equity and inclusion, thus overcoming barriers and ensuring comprehensive population reach in HIV prevention studies.

Aggression is ubiquitous among social species and can function to maintain social dominance hierarchies. The African cichlid fish Astatotilapia burtoni is an ideal study species for studying aggression due to their dominance hierarchy and robust behavioral repertoire. To further understand the potential sex differences in aggression in this species, we characterized aggression in male and female A. burtoni in a mirror assay. We then quantified neural activation patterns in brain regions of the social behavior network (SBN) to investigate if differences in behavior are reflected in the brain with immunohistochemistry by detecting the phosphorylated ribosome marker phospho-S6 ribosomal protein (pS6), a marker for neural activation. We found that A. burtoni perform both identical and sex-specific aggressive behaviors in response to a mirror assay. Females had greater pS6 immunoreactivity than males in the Vv (ventral part of the ventral telencephalon), a homolog of the lateral septum in mammals. Males but not females had higher pS6 immunoreactivity in the ATn after the aggression assay. The ATn (anterior tuberal nucleus) is a homolog of the ventromedial hypothalamus in mammals, which is strongly implicated in the regulation of aggression in males. Several regions also have higher pS6 immunoreactivity in negative controls than fish exposed to a mirror, implicating a role for inhibitory neural processes in suppressing aggression until a relevant stimulus is present. Male and female A. burtoni display both similar and different behavioral patterns in aggression in response to a mirror assay. There are also sex differences in the corresponding neural activation patterns in the SBN. In mirror males but not females, the ATn clusters with the POA, revealing a functional connectivity of these regions that is triggered in an aggressive context in males. These findings suggest that distinct neural circuitry underlie aggressive behavior in male and female A. burtoni, serving as a foundation for future work investigating the molecular and neural underpinnings of sex differences in behavior in this species to reveal fundamental insights into understanding aggression.

Accumulating evidence indicates that unpredictable signals in early life represent a unique form of adverse childhood experiences (ACEs) associated with disrupted neurodevelopmental trajectories in children and adolescents. The Questionnaire of Unpredictability in Childhood (QUIC) was developed to assess early life unpredictability [1], encompassing social, emotional, and physical unpredictability in a childs environment, and has been validated in three independent cohorts. However, the importance of identifying ACEs in diverse populations, including non-English speaking groups, necessitates translation of the QUIC. The current study aims to translate and validate a Spanish language version of the QUIC (QUIC-SP) and assess its associations with mental and physical health. Spanish-speaking participants (N = 285) were recruited via the online market crowdsourcing platform, Amazon Mechanical Turk (MTurk), and completed an online survey that included the QUIC-SP and validated Spanish language assessments of physical and mental health. The QUIC-SP demonstrated excellent psychometric properties and similar mean scores, endorsement rates, and internal reliability to the English language version, thus establishing its validity among Spanish-speaking adults. Higher QUIC-SP scores, indicating greater unpredictability in early life, predicted increased symptoms of anxiety, anhedonia, depression, and poorer physical health. Given significant racial and ethnic disparities in health, the QUIC-SP may serve as a valuable tool to address the public health consequences of ACEs among Spanish-speaking populations.

BackgroundAs people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health.SettingThis study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of 6 months or less to live. We examined the relationship between QOL, mental health, and research participation.MethodsStructured assessments were used to collect comprehensive data on QOL and mental health.ResultsFrom 2017 to 2023, 35 PWH in their final stages of life who were actively engaged in cure-related research were enrolled. Their median age was 62.7 years, and most were White or otherwise non-Hispanic/non-Latino (90.6%), and male (86.7%). Changes in QOL and the presence of neurologic and psychiatric conditions, with a focus on depression and anxiety, were the primary outcomes assessed in this study. Participants had stable QOL scores throughout the study. There was an inverse relationship between QOL and Beck Depression Inventory scores, with higher mean QOL scores being associated with lower mean Beck Depression Inventory scores ( P < 0.001).ConclusionsQOL remained stable among PWH who participate in cure-related research at EOL. The inverse relationship between QOL and depressive symptoms suggests that participation in cure-related research may improve QOL or reduce depressive symptoms in this population. Future interventions should look into ways to improve the well-being of PWH at EOL through research and customized mental health interventions.

Parenting that is warm and supportive has been consistently linked to better emotion regulation in children, but less is known about this association in adolescents. Adolescence is thought to be an important period for emotion regulation development given that it coincides with the emergence of mental health issues. Respiratory sinus arrhythmia (RSA) is a measure of parasympathetic regulation linked to emotion and behavior regulation. Despite the well-documented links between parenting practices and emotion regulation, and between RSA and emotion regulation, few studies have focused on the association between positive parenting and adolescent RSA or included both mothers and fathers. The current study analyzed the influence of warm parenting throughout adolescence (ages 10-16) on basal RSA at age 17 in 229 Mexican-origin youths. Latent-growth curve models were used to analyze associations between maternal and paternal warmth and baseline RSA. Changes in maternal, but not paternal, warmth from age 10 to 16 were related to youths' basal RSA at age 17. Specifically, youths who perceived increasing (or less decreasing) maternal warmth across adolescence had higher basal RSA. This finding suggests that positive maternal parenting experiences during adolescence "get under the skin" to enhance parasympathetic functioning that supports youths' emotion regulation capacities.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Background and aimsVideo games are a common form of entertainment in adolescents, which may result in gaming habits characterized by impairment to reward-related decision-making. The aim of the current study was to investigate the relationship between reward processing and symptoms of gaming addiction in adolescents.MethodsData from three consecutive follow-up years (years 2, 3 and 4) of the Adolescent Brain Cognitive Development (ABCD) Study were analyzed (n = 6,143, total observations = 12,745, mean age at year-2 = 12 years). Participants completed the Video Game Addiction Questionnaire (VGAQ) at each visit. Discrete stages of reward processing were measured at the year-2 visit using the Monetary Incentive Delay task while the participant completed a functional magnetic resonance imaging (fMRI) scan. Bayesian hierarchical linear models were employed to examine the longitudinal association between reward processing in regions of interest at year-2 and VGAQ scores over time.ResultsLower activation in the bilateral caudate during the anticipation of a large reward (β = -0.87, 95% CI: -1.68, -0.07) was associated with greater VGAQ scores over time. This implies that for each one-unit increase in brain activity in the caudate, there was an associated 0.87-point decrease in symptoms of gaming addiction as measured by the VGAQ. No association was found between reward feedback and VGAQ scores.Discussion and conclusionsThe findings suggest that abnormal reward processing in the caudate nucleus is associated with symptoms of gaming addiction in adolescents. These results provide a clearer understanding of the brain mechanisms involved in gaming addiction, which could inform future preventive and therapeutic strategies.

ImportanceIdentification of individuals at high risk of alcohol use disorder (AUD) and subsequent application of prevention and intervention programs has been reported to decrease the incidence of AUD. The polygenic score (PGS), which measures an individual's genetic liability to a disease, can potentially be used to evaluate AUD risk.ObjectiveTo assess the estimability and generalizability of the PGS, compared with family history and ADH1B, in evaluating the risk of AUD among populations of European ancestry.Design, setting, and participantsThis genetic association study was conducted between October 1, 2023, and May 21, 2024. A 2-stage design was used. First, the pruning and thresholding method was used to calculate PGSs in the screening stage. Second, the estimability and generalizability of the best PGS was determined using 2 independent samples in the testing stage. Three cohorts ascertained to study AUD were used in the screening stage: the Collaborative Study on the Genetics of Alcoholism (COGA), the Study of Addiction: Genetics and Environment (SAGE), and the Australian Twin-Family Study of Alcohol Use Disorder (OZALC). The All of Us Research Program (AOU), which comprises participants with diverse backgrounds and conditions, and the Indiana Biobank (IB), consisting of Indiana University Health system patients, were used to test the best PGS. For the COGA, SAGE, and OZALC cohorts, cases with AUD were determined using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fifth Edition (DSM-5) criteria; controls did not meet any criteria or did not have any other substance use disorders. For the AOU and IB cohorts, cases with AUD were identified using International Classification of Diseases, Ninth Revision (ICD-9) or International Classification of Diseases, Tenth Revision (ICD-10) codes; controls were aged 21 years or older and did not have AUD.ExposureThe PGS was calculated using single-nucleotide variants with concordant effects in 3 large-scale genome-wide association studies of AUD-related phenotypes.Main outcomes and measuresThe main outcome was AUD determined with DSM-IV or DSM-5 criteria and ICD-9 or ICD-10 codes. Generalized linear mixed models and logistic regression models were used to analyze related and unrelated samples, respectively.ResultsThe COGA, SAGE, and OZALC cohorts included a total of 8799 samples (6323 cases and 2476 controls; 50.6% were men). The AOU cohort had a total of 116 064 samples (5660 cases and 110 404 controls; 60.4% were women). The IB cohort had 6373 samples (936 cases and 5437 controls; 54.9% were women). The 5% of samples with the highest PGS in the AOU and IB cohorts were approximately 2 times more likely to develop AUD (odds ratio [OR], 1.96 [95% CI, 1.78-2.16]; P = 4.10 × 10-43; and OR, 2.07 [95% CI, 1.59-2.71]; P = 9.15 × 10-8, respectively) compared with the remaining 95% of samples; these ORs were comparable to family history of AUD. For the 5% of samples with the lowest PGS in the AOU and IB cohorts, the risk of AUD development was approximately half (OR, 0.53 [95% CI, 0.45-0.62]; P = 6.98 × 10-15; and OR, 0.57 [95% CI, 0.39-0.84]; P = 4.88 × 10-3) compared with the remaining 95% of samples; these ORs were comparable to the protective effect of ADH1B. PGS had similar estimabilities in male and female individuals.Conclusions and relevanceIn this study of AUD risk among populations of European ancestry, PGSs were calculated using concordant single-nucleotide variants and the best PGS was tested in targeted datasets. The findings suggest that the PGS may potentially be used to evaluate AUD risk. More datasets with similar AUD prevalence as in general populations are needed to further test the generalizability of PGS.

OBJECTIVE: To examine the relationship between the penetration (or reach) of a national program aiming to integrate mental health clinicians into all primary care clinics (PC-MHI) and rates of guideline-concordant follow-up and treatment among clinic patients newly identified with depression in the Veterans Health Administration (VA). DATA SOURCES/STUDY SETTING: 15,155 screen-positive patients 607,730 patients with 2-item Patient Health Questionnaire scores in 82 primary care clinics, 2015-2019. STUDY DESIGN: In this retrospective cohort study, we used established depression care quality measures to assess primary care patients who (a) newly screened positive (score ≥3) and (b) were identified with depression by clinicians via diagnosis and/or medication (n = 15,155; 15,650 patient-years). Timely follow-up included ≥3 mental health, ≥3 psychotherapy, or ≥3 primary care visits for depression. Minimally appropriate treatment included ≥4 mental health visits, ≥3 psychotherapy, or ≥60 days of medication. In multivariate regressions, we examined whether higher rates of PC-MHI penetration in clinic (proportion of total primary care patients in a clinic who saw any PC-MHI clinician) were associated with greater depression care quality among cohort patients, adjusting for year, healthcare system, and patient and clinic characteristics. DATA COLLECTION/EXTRACTION METHODS: Electronic health record data from 82 VA clinics across three states. PRINCIPAL FINDINGS: A median of 9% of all primary care patients were seen by any PC-MHI clinician annually. In fully adjusted models, greater PC-MHI penetration was associated with timely depression follow-up within 84 days (∆P = 0.5; SE = 0.1; p

ObjectiveIdentifying persons with HIV (PWH) at increased risk for Alzheimer's disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.DesignWe examined 92 PWH from the CHARTER Program, ages 45-68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).ResultsAt baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.ConclusionsEpisodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Associating different aspects of experience with discrete events is critical for human memory. A potential mechanism for linking memory components is phase precession, during which neurons fire progressively earlier in time relative to theta oscillations. However, no direct link between phase precession and memory has been established. Here we recorded single-neuron activity and local field potentials in the human medial temporal lobe while participants (n = 22) encoded and retrieved memories of movie clips. Bouts of theta and phase precession occurred following cognitive boundaries during movie watching and following stimulus onsets during memory retrieval. Phase precession was dynamic, with different neurons exhibiting precession in different task periods. Phase precession strength provided information about memory encoding and retrieval success that was complementary with firing rates. These data provide direct neural evidence for a functional role of phase precession in human episodic memory.

Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer's disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2-7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype. Next, we run machine learning on AD-control data from the Alzheimer's Disease Neuroimaging Initiative using brain change trajectories conditioned on age, to identify AD-sensitive features and model their change in healthy adults. Genetic AD-risk linked with multivariate change across many AD-sensitive features, and we show most individuals over age ~50 are on an accelerated trajectory of brain loss in AD-sensitive regions. Finally, high genetic risk adults with elevated brain change showed more memory decline through adulthood, compared to high genetic risk adults with less brain change. Our findings suggest quantitative AD risk factors are detectable in healthy individuals, via a shared pattern of ageing- and AD-related neurodegeneration that occurs along a continuum and tracks memory decline through adulthood.

AimsAnxiety disorders are prevalent and anxiety symptoms (ANX) co-occur with many psychiatric disorders. We aimed to identify genomic loci associated with ANX, characterize its genetic architecture, and genetic overlap with psychiatric disorders.MethodsWe included a genome-wide association study of ANX (meta-analysis of UK Biobank and Million Veterans Program, n = 301,732), schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), and validated the findings in the Norwegian Mother, Father, and Child Cohort (n = 95,841). We employed the bivariate causal mixture model and local analysis of covariant association to characterize the genetic architecture including overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of loci associated with anxiety and shared with psychiatric disorders.ResultsAnxiety was polygenic with 12.9k genetic variants and overlapped extensively with psychiatric disorders (4.1k-11.4k variants) with predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 119 novel loci for anxiety by conditioning on the psychiatric disorders, and loci shared between anxiety and MD n=47 , BIP n=33 , SCZ n=71 , ADHD n=20 , and ASD n=5 . Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways including cell adhesion and neurofibrillary tangle compared with genes annotated to the shared loci.ConclusionsAnxiety is highly polygenic phenotype with extensive genetic overlap with psychiatric disorders, and we identified novel loci for anxiety implicating new molecular pathways. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified molecular underpinnings may lead to potential drug targets.

Comorbid cannabis use disorder (CUD) is disproportionately high in people with bipolar disorder (BD) and has been associated with worsening of BD symptoms. However, many people with BD report regularly using cannabis to ameliorate symptoms, including sleep disturbances. Sleep and circadian rhythm disturbances are hallmark features of BD that often precede the onset of mood symptoms. Genetic studies indicate that circadian disruption may predispose individuals towards both problematic cannabis use and BD, rather than cannabis use directly impacting BD symptoms. To further disentangle these hypotheses, we aimed to investigate the relationship between chronotype, cannabis use disorder (CUD) and BD mood symptoms. Data from 212 participants with BD I from the Pharmacogenomics of Bipolar Disorder study dataset were analyzed for this study. Participants were stratified by those diagnosed with co-morbid CUD and BD symptom variables, including the mean number of mood episodes per year and age of mood symptom onset for both depression and mania symptoms. The Basic Language Morningness scale (BALM) was used to assess chronotype. There was no interaction between morningness levels and CUD on BD symptoms, however both lower morningness and CUD were independently associated with earlier age of mood symptom onset. However, patients who reported initiating cannabis use post mood symptom onset had an earlier mood symptom age of onset compared to those who reported initiating cannabis use prior to mood symptom onset. These findings could provide further evidence that circadian rhythm disruption could be an underlying factor that predisposes individuals toward both CUD and BD.

INTRODUCTION: Locus of control (LoC) refers to ones expectation that life outcomes and (mis)fortune are driven largely by ones own actions or abilities (internal LoC) or by external factors (e.g., powerful others, chance; external LoC). There is a large literature demonstrating an association between internal LoC and positive mental health outcomes. However, this research is conducted mostly in high-income, Global North settings, with limited consideration of cross-cultural variability. This short report explores how LoC relates to mental health when considered in a less-studied context: in a setting of stark structural violence and in relation to supernatural agents. METHODS: I conducted a community-based survey in rural Haiti (n = 322) that assessed sent spirit-related locus of control (LoC-S) and mental health. RESULTS: Among individuals experiencing higher levels of daily stressors, depressive and anxiety symptoms were high regardless of LoC-S. However, for individuals facing low-to-moderate daily stressors, external LoC-S (believing one does not have control in relation to sent spirits) was associated with lower depressive and anxiety symptoms, though this interaction did not hold for anxiety after controlling for covariates. Though initially a nonintuitive finding, I contextualize this outcome in relation to ethnographic work in Haiti, showing that the ability to explain misfortune via the supernatural world can serve as a form of blame displacement. CONCLUSION: In a context where extreme structural violence means that individuals realistically have little control over their lives, an external LoC better reflects lived experience, helping explain the association with better mental health outcomes.

To investigate the relationship of predisposing, enabling, need, and immigration-related factors to tele-mental health services utilization among California adults, we conducted a secondary analysis of two waves of the California Health Interview Survey (CHIS) collected between 2015 and 2018 (N = 78,345). A series of logistic regression models were conducted to examine correlates and predictors to tele-mental health services use. Approximately 1.3% reported the use of tele-mental health services. Overall, health insurance status, severe psychological distress, perceived need for mental health services, and identifying as Asian, remained strong predictors for tele-mental health service use. When accounting for all factors, we found that being a non-citizen was associated with lower odds of tele-mental health service use (AOR = 0.47, CI = 0.26, 0.87, p

Dopaminergic projections from the ventral tegmental area (VTA) to limbic regions play a key role in the initiation and maintenance of substance use; however, the relationship between mesolimbic resting-state functional connectivity (RSFC) and alcohol use during development remains unclear. We examined the associations between alcohol use and VTA RSFC to subcortical structures in 796 participants (12-21 years old at baseline, 51 % female) across 9 waves of longitudinal data from the National Consortium on Alcohol and Neurodevelopment in Adolescence. Linear mixed effects models included interactions between age, sex, and alcohol use, and best fitting models were selected using log-likelihood ratio tests. Results demonstrated a positive association between alcohol use and VTA RSFC to the nucleus accumbens. Age was associated with VTA RSFC to the amygdala and hippocampus, and an age-by-alcohol use interaction on VTA-globus pallidus connectivity was driven by a positive association between alcohol and VTA-globus pallidus RSFC in adolescence, but not adulthood. On average, male participants exhibited greater VTA RSFC to the amygdala, nucleus accumbens, caudate, hippocampus, globus pallidus, and thalamus. Differences in VTA RSFC related to age, sex, and alcohol, may inform our understanding of neurobiological risk and resilience for alcohol use and other psychiatric disorders.

IntroductionSexual minority (e.g., bisexual, gay, lesbian, queer) and gender minority (e.g., transgender, non-binary, gender expansive) individuals (SGMI) experience higher rates of alcohol and other substance use disorders than their heterosexual and cisgender (i.e., non-transgender) counterparts. 12-Step programs are currently the most common source of support for alcohol and other substance use-related problems in the United States. Little is known about rates and levels of participation and outcomes of SGMI in 12-Step programs. Examining SGMI with a lifetime alcohol or other substance use disorder, this study aims to: 1) describe lifetime attendance rates (any vs. none) and levels of participation (number of program activities) in 12-Step groups among SGMI overall and compare rates of attendance and levels of participation across sexual and gender minority identities and 2) determine how lifetime level of participation in 12-Step programs relates to past-year alcohol and other substance use outcomes.MethodsWe used data collected through The PRIDE Study, a national, large-scale, longitudinal health study of adult SGMI, administering supplemental questions to assess alcohol and other substance use disorders and 12-step participation. Zero-Inflated Negative Binomial models (N = 1353) run with sexual and gender identities as predictors of lifetime 12-step attendance (yes/no) and level of 12-Step participation determine if greater levels of 12-Step participation were associated with lower levels of past-year Alcohol and Substance Use Disorder (AUD & SUD) symptoms. The study ran models for those with lifetime AUD (n = 1074) and SUD (n = 659) separately.ResultsParticipants who engaged in greater levels of 12-Step participation had lower levels of past-year AUD and SUD symptoms. Gay and queer respondents with AUD were more likely and lesbian respondents with SUD were less likely than other participants to have ever participated in 12-Step programs. All other associations between sexual/gender identities and 12-Step participation disappeared when age was added to the model.ConclusionsThis study provides preliminary evidence that 12-Step participation may be an effective resource for reducing AUD and SUD symptoms among SGMI. Younger SGMI and SGMI holding sexual/gender identities other than gay and queer may require additional support to initiate participation in 12-Step programs.

The hypocretin (Hcrt) system modulates arousal and anxiety-related behaviors and has been considered as a novel treatment target for stress-related affective disorders. We examined the effects of Hcrt acting in the nucleus accumbens shell (NAcSh) and anterodorsal bed nucleus of the stria terminalis (adBNST) on social behavior in male and female California mice (Peromyscus californicus). In female but not male California mice, infusion of Hcrt1 into NAcSh decreased social approach. Weak effects of Hcrt1 on social vigilance were observed in both females and males. No behavioral effects of Hcrt1 infused into the adBNST were observed. Analyses of sequencing data from California mice and Mus musculus NAc showed that Hcrtr2 was more abundant than Hcrtr1, so we infused the selective Hcrt receptor 2 antagonist into the NAcSh, which increased social approach in females previously exposed to social defeat. A calcium imaging study in the NAcSh of females before and after stress exposure showed that neural activity increased immediately following the expression of social avoidance but not during freezing behavior. This observation is consistent with previous studies that identified populations of neurons in the NAc that drive avoidance. Intriguingly, calcium transients were not affected by stress. These data suggest that hypocretin acting in the NAcSh plays a key role in modulating stress-induced social avoidance.

Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type-specific mechanisms underlying psychedelic-induced behavioral states.

In utero gene editing with mRNA-based therapeutics has the potential to revolutionize the treatment of neurodevelopmental disorders. However, a critical bottleneck in clinical application has been the lack of mRNA delivery vehicles that can efficiently transfect cells in the brain. In this report, we demonstrate that in utero intracerebroventricular (ICV) injection of densely PEGylated lipid nanoparticles (ADP-LNPs) containing an acid-degradable PEG-lipid can safely and effectively deliver mRNA for gene editing enzymes to the fetal mouse brain, resulting in successful transfection and editing of brain cells. ADP-LNPs containing Cre mRNA transfected 30% of the fetal brain cells in Ai9 mice and had no detectable adverse effects on fetal development and postnatal growth. In addition, ADP-LNPs efficiently transfected neural stem and progenitor cells in Ai9 mice with Cre mRNA, which subsequently proliferated and caused over 40% of the cortical neurons and 60% of the hippocampal neurons to be edited in treated mice 10 weeks after birth. Furthermore, using Angelman syndrome, a paradigmatic neurodevelopmental disorder, as a disease model, we demonstrate that ADP-LNPs carrying Cas9 mRNA and gRNA induced indels in 21% of brain cells within 7 days postpartum, underscoring the precision and potential of this approach. These findings demonstrate that LNP/mRNA complexes have the potential to be a transformative tool for in utero treatment of neurodevelopmental disorders and set the stage for a frontier in treating neurodevelopmental disorders that focuses on curing genetic diseases before birth.

BACKGROUND: Weight stigma is a fundamental cause of health inequality. Body positivity may be a counterbalance to weight stigma. Social media is replete with weight-stigmatizing content and is a driver of poor mental health outcomes; however, there remains a gap in understanding its potential to mitigate the prevalence and impact of harmful messaging and to promote positive effects on a large scale. OBJECTIVE: We selected musical artist Lizzo, whose brand emphasizes body positivity and empowerment, for an instrumental case study on the discourse on social media and specifically Instagram. We focused on 3 domains, including body positivity, physical health, and emotional well-being. These domains challenge social norms around weight and body size and have the potential to positively affect the physical and psychological health of people with diverse body sizes. METHODS: We evaluated posts by Lizzo, comments from Instagram users, and replies to comments over a 2-month period (October 11 to December 12, 2019). Two coders rated Lizzos posts and Instagram users comments for their sentiments on the 3 domains. Replies to Instagram users comments were assessed for their reactions to comments (ie, did they oppose or argue against the comment or did they support or bolster the comment). Engagement metrics, including the number of likes, were also collected. RESULTS: The final sample included 50 original posts by Lizzo, 250 comments from Instagram users, and 1099 replies to comments. A proportion of Lizzos content included body positive sentiments (34%) and emotional well-being (18%); no posts dealt explicitly with physical health. A substantial amount Instagram users comments and replies contained stigmatizing content including the use of nauseated and vomiting emojis, implications that Lizzos body was shameful and should be hidden away, accusations that she was promoting obesity, and impeachments of Lizzos health. In spite of the stigmatizing content, we also discovered content highlighting the beneficial nature of having positive representation of a Black woman living in a larger body who is thriving. Moreover, analysis of the discourse between users illustrated that stigmatizing expressions are being combated online, at least to some degree. CONCLUSIONS: This study demonstrates that Lizzo has exposed millions of social media users to messages about body positivity and provided more visibility for conversations about weight and shape. Future research should examine the extent to which body positive messages can lead to greater acceptance of individuals living in larger bodies. Instagram and other social media platforms should consider ways to reduce body-shaming content while finding ways to promote content that features diverse bodies. Shifting the landscape of social media could decrease stereotypes about weight and shape while increasing dialog about the need for greater acceptance and inclusion of people with diverse bodies.

ObjectiveThis study aimed to investigate the relationships between four types of perceived discrimination (based on race and ethnicity, nationality/country of origin, gender identity, weight/body size), individually and cumulatively; positive childhood experiences (PCEs); and behavioral symptoms among pre-adolescent youth.MethodsThis study was a secondary analysis of data from the Adolescent Brain Cognitive Development (ABCD) Study, a US-based cohort study of pre-adolescent youth in the United States (N = 10,915). Our outcome was emotional/behavioral symptoms measured by the Child Behavior Checklist. Primary exposures were four types of discrimination, a count of 0-5 PCEs, and other adverse childhood experiences (ACEs). Multiple logistic regression models were used to estimate the relationship between perceived discrimination and clinical-range behavioral symptoms, including the role of PCEs and ACEs.ResultsWeight discrimination was the most frequent exposure (n = 643, 5.9%). Race and weight perceived discrimination were associated with clinical-range externalizing and internalizing symptoms, respectively, but these associations were non significant once other ACEs were added to models. Cumulative discrimination was associated with clinical-range Child Behavior Checklist (CBCL) scores, even when accounting for other ACEs (aOR=1.47, 95% CI=1.2-1.8). PCEs slightly reduced the strength of this relationship and were independently associated with reduced symptoms (aOR=0.82, 95% CI=0.72-0.93).ConclusionsResults of this national study suggest cumulative discrimination can exert emotional/behavioral health harm among youth. PCEs were independently associated with reduced behavioral symptoms. There is a need for further research on how to prevent discrimination and bolster PCEs by targeting upstream social inequities in communities.

BackgroundDepression is a pervasive symptom in patients with gynecological cancer undergoing chemotherapy.ObjectivesPurposes were to identify subgroups of patients with distinct depression profiles and evaluate for differences in demographic and clinical characteristics, severity of common symptoms, and quality of life (QOL) outcomes among these subgroups.MethodsPatients with gynecological cancer (n = 231) completed the Center for Epidemiologic Studies-Depression Scale 6 times over 2 cycles of chemotherapy. All of the other measures were completed prior to the second or third cycle of chemotherapy. Latent profile analysis was done to identify the distinct depression profiles. Differences were evaluated using parametric and nonparametric tests.ResultsThree distinct profiles were identified: low (60.1%), high (35.1%), and very high (4.8%). Compared with low class, the other 2 classes had lower functional status and were more likely to self-report a diagnosis of depression. Patients in the 2 worse profiles reported a higher comorbidity burden, higher levels of trait and state anxiety, sleep disturbance, and fatigue, as well as lower levels of cognitive function and poorer QOL. State and trait anxiety, evening fatigue, and sleep disturbance scores exhibit a "dose-response effect" (ie, as the depression profile worsened, the severity of these symptoms increased).ConclusionsAlmost 40% of our sample experienced high or very high levels of depression across 2 cycles of chemotherapy.Implications for practiceClinicians can use the identified risk factors to identify high patients risk and provide tailored psychological interventions aimed to decrease symptom burden and prevent decrements in QOL.

ObjectiveThe COVID-19 pandemic had profound effects on society, including those living with chronic pain. This study sought to examine pandemic impacts on individuals enrolled in pragmatic clinical trials focused on nonpharmacological treatments for chronic pain.MethodsWe evaluated responses to a questionnaire on COVID-19 impacts that had been administered to participants (n=2024) during study enrollment in 3 pragmatic clinical trials for chronic pain treatment. All trials were part of the National Institutes of Health (NIH)-Department of Veterans Affairs (VA)-Department of Defense (DOD) Pain Management Collaboratory. COVID-19-related impacts on access to health care, mental health, finances, ability to meet basic needs, and social support were assessed.ResultsPandemic impacts were found in all domains assessed, including access to health care, mental and emotional health, ability to meet basic needs, finances, and social support. Impacts varied by demographic and clinical characteristics. The participants most negatively impacted by the pandemic were younger, Black or Latino, female, more educated, and unemployed and had screened positive for depression. No impact differences were found with regard to alcohol use disorder screenings or a prior history of COVID-19. Higher levels of pain were associated with worse pandemic impacts, and negative impacts declined over time.ConclusionsNegative impacts of the pandemic on individuals living with chronic pain cut across aspects of life that are also central to effective pain management, including access to health care, social support, and mental and emotional health, with differential impacts found across key demographic and clinical factors. These findings should yield consideration of pandemic impacts in clinical practice and as moderating effects of treatment outcomes in clinical trials conducted during the pandemic.

IntroductionThe ability to objectively measure chronic stress has important implications for research, prevention, and treatment. Cortisol is currently the most used biological marker in the investigation of stress and can be measured via blood, saliva, and urine; however, these methods have disadvantages. The measurement of cortisol in hair is a more recently developed method that quantifies the cumulative production of cortisol over longer periods of time. Given the potential benefits of hair as a chronic stress biometric, research with this novel method is burgeoning, yet rarely involves transgender ("trans") populations, despite high levels of reported stress among trans people due to experiences of stigma and discrimination. Since hair is a key part of gender presentation, trans people might be less likely than cisgender people to donate hair for research. To explore the feasibility and acceptability of hair collection for use as a stress biometric with trans women, we nested a study into an ongoing clinical trial in São Paulo, Brazil, "Manas por Manas" (Sisters for Sisters). Here, we describe the hair biometric substudy protocol, as well as the feasibility and acceptability of collecting hair in the study cohort.MethodsWe randomly selected a subsample (n = 180) from the Manas por Manas cohort (n = 392), all of whom are trans women, age 18 or older. We messaged participants via phone, WhatsApp, or social media for at least three attempted contacts. Study visits included four components: (1) video introduction, including a demonstration of hair sampling; (2) informed consent; (3) a brief survey with the validated Short Stress Overload Scale (translated to Portuguese) and questions on hair care that could moderate stress hormone results; and (4) hair sample collection. Hair samples were collected and stored using validated protocols. Participants were reimbursed for travel costs.ResultsBetween April and December 2022, we messaged with 143 individuals out of the 180 sampled (79%) and invited them to participate in the study. Of those invited to participate, we scheduled study visits with 102 people (71.3% of those invited to participate), of whom 100 attended their study visits and completed all activities. Two people did not attend their study visits and stopped communication. Of those who were invited to participate and declined a study visit, four individuals declined due to the hair sample collection procedures (2.8% of those invited to participate). Other reasons for declining to participate included having moved (n = 7), lack of time (n = 11), not interested in research participation (n = 8), or unknown/stopped responding to messages (n = 11). Most participants reported that they chemically treated their hair to bleach, color, or straighten it, which could impact laboratory assays.ConclusionWe found hair sampling for stress measurement to be feasible and acceptable to our participants. We successfully completed all study activities for our desired sample size, and most recruited individuals volunteered to participate. Reasons provided for declining study participation reflected general barriers to research participation, with only four people declining due to hair sample collection procedures.

BackgroundDuring the COVID-19 pandemic, many people lacked access to group fitness opportunities due to elevated risk of infection, lockdown, and closure of exercise facilities. Additionally, many people experienced higher than average rates of mental health burden (eg, anxiety and stress). To help address these needs, an existing in-person community exercise class, taught by a faculty member from an academic medical center, transitioned to an online synchronous (OS) physical fitness class via the Zoom (Zoom Video Communications) videoconferencing platform. As such, the instructor advertised the OS fitness classes through an existing email list of community members and university faculty, staff, students, or alumni email listservs. This telewellness intervention sought to create a sense of community, build social support, and promote physical and mental wellness during the COVID-19 pandemic.ObjectiveOur aim was to determine the perceived mental and physical health benefits of attending an OS fitness class for community members, including health care workers. We also assessed the use and functionality of related technologies necessary for delivering and attending the fitness classes.MethodsAn online survey questionnaire was created and tested to collect quantitative and qualitative data for an exploratory study. Data were collected to evaluate the fitness class, motivation, perceived health benefits, and related technologies. A convenience sample of people who had participated in the OS fitness classes was recruited for this study via an emailed recruitment flyer.ResultsA total of 51 participants accessed and completed the survey questionnaire. Survey participants consisted of 28 of 51 (55%) with a university affiliation, 17 of 51 (33%) with no university affiliation, and 6 of 51 (12%) who declined to state. The largest group of participants reporting full-time employment (18/51, 35%) also reported university affiliation with the academic medical center. In this group, 13 of 51 (25%) participants reported full-time employment, university affiliation, and doctoral degrees. High overall exercise class satisfaction was observed in the survey responses (mean 4.0, SD 1). Data analyses revealed significant perceived value of both mental and physical health benefits as motivating factors for participating in the OS fitness class. Challenges were identified as not being able to receive individual feedback from the instructor and the inability of some participants to see if they were in sync with the rest of the class.ConclusionsResults provide preliminary support for the use of online videoconferencing fitness platforms to promote wellness and facilitate group exercise in the community during times of high infection risk. Future studies should continue to explore perceived benefits, mental and physical wellness, best practices, and the design of related technologies.

Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2-13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.

IntroductionThe potential utility of subjective cognitive decline (SCD) as an early risk marker of Alzheimer's disease and related dementias is under consideration. We examined associations between SCD and cognitive change among middle-aged and older Hispanic/Latino adults living in the United States.MethodsThe short-form Everyday Cognition Scale (ECog-12) was assessed to generate global, executive function, and memory-related SCD scores. We used survey generalized regressions to model the change in learning, memory, verbal fluency, executive function, and global cognitive performance over 7 years as a function of SCD (at Visit 2).ResultsThe mean age was 56.37 ± 8.10 years at Visit 1 (n = 6225). Higher ECog-12 was associated with greater decline in global cognitive performance (ECog-12 global: B = -0.17, standard error [SE] = 0.02; ECog-12 executive: B = -0.15, SE = 0.02; ECog-12 memory: B = -0.14, SE = 0.02, p's

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The 'big five' personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses, including depression, anxiety and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Here, utilizing the Million Veteran Program cohort, we conducted a genome-wide association study in individuals of European and African ancestry. Adding other published data, we performed genome-wide association study meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 208, 14, 3, 2 and 7 independent genome-wide significant loci associated with neuroticism, extraversion, agreeableness, conscientiousness and openness, respectively. These findings represent 62 novel loci for neuroticism, as well as the first genome-wide significant loci discovered for agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety, while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.

IntroductionFew studies have examined the relationship between education and cognition among the oldest-old.MethodsCognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (

Despite established efficacy for oral pre-exposure prophylaxis (PrEP) in reducing HIV incidence, multi-level barriers within the health system, clinics, and the processes that shape practice have hindered service delivery and subsequent population-level effects. We applied the Consolidated Framework for Implementation Research (CFIR) to assess the context of PrEP delivery for adolescent girls and young women (AGYW) in rural South Africa and identify the factors supporting and impeding PrEP implementation to develop strategies to improve PrEP delivery. Between 2021 and 2022, we conducted in-depth interviews with five young women with PrEP use experience and 11 healthcare providers as well as four key informant stakeholder interviews. Tailored interviews organized around the CFIR domains provided multiple perspectives on the inter-connected processes, gaps, and opportunities between health systems, clinics, communities, and PrEP services. Shifts in PrEP policies, funding pressures, and inconsistent communications from the National Department of Health spurred fragmented planning, engagement, execution, and monitoring of PrEP delivery processes within clinics already struggling to address multiple population health needs. Resulting challenges included: conflicting priorities within clinics and across NGO partners, unclear goals and targets, staffing and space constraints, and insufficient community engagement. Individual clinics' implementation climate and readiness to deliver PrEP varied in terms of operational plans and delivery models. Interviewees reported complexity of initiation procedures and support for PrEP maintenance, with opportunities to improve systems communications and processes to facilitate integrated services and more user-friendly experiences. Applying CFIR identified opportunities to strengthen PrEP delivery across levels within this complex service delivery setting.

ObjectiveIndividuals with unhealthy alcohol use and comorbid depression or anxiety may be vulnerable to alcohol use escalation in times of stress such as the COVID-19 pandemic. Among a cohort of individuals with pre-pandemic unhealthy drinking, we compared changes in alcohol use by whether people had a depression or anxiety diagnosis and examined whether mental health treatment was related to these changes.MethodUsing electronic health record data from Kaiser Permanente Northern California, we analyzed drinking changes during the pandemic (3/1/2020-6/30/2022) among adults identified in primary care with unhealthy alcohol use (exceeding daily/weekly recommended limits) pre-pandemic (1/1/2019-2/29/2020). Outcomes were mean changes in number of heavy drinking days (prior 3 months), drinks/week, drinks/day, and drinking days/week. Multivariable linear regression models were fit to (a) compare outcomes of patients with depression or anxiety diagnoses to those without, and (b) among patients with depression or anxiety, estimate associations between mental health treatment and outcomes.ResultsThe sample included 62,924 adults with unhealthy alcohol use, of whom 12,281 (19.5%) had depression or anxiety. On average, alcohol use significantly decreased across all measures during the pandemic; however, patients with depression or anxiety had greater decreases in drinks/week (adjusted mean difference [aMD] [CI] = -0.34 [-0.55, -0.12]) and drinking days/week (-0.15 [-0.20, -0.10]). No associations were found between mental health treatment and changes in drinking.ConclusionsContrary to expectations, patients with unhealthy alcohol use and depression or anxiety decreased alcohol use more than those without depression or anxiety during COVID-19, regardless of whether they accessed mental health services.

Early stages of Alzheimer's disease (AD) are associated with volume reductions in specific subregions of the medial temporal lobe (MTL). Using a manual segmentation method-the Olsen-Amaral-Palombo (OAP) protocol-previous work in healthy older adults showed that reductions in grey matter volumes in MTL subregions were associated with lower scores on the Montreal Cognitive Assessment (MoCA), suggesting atrophy may occur prior to diagnosis of mild cognitive impairment, a condition that often progresses to AD. However, current "gold standard" manual segmentation methods are labour intensive and time consuming. Here, we examined the utility of Automatic Segmentation of Hippocampal Subfields (ASHS) to detect volumetric differences in MTL subregions of healthy older adults who varied in cognitive status as determined by the MoCA. We trained ASHS on the OAP protocol to create the ASHS-OAP atlas and then examined how well automated segmentation replicated manual segmentation. Volumetric measures obtained from the ASHS-OAP atlas were also contrasted against those from the ASHS-PMC atlas, a widely used atlas provided by the ASHS team. The pattern of volumetric results was similar between the ASHS-OAP atlas and manual segmentation for anterolateral entorhinal cortex and perirhinal cortex, suggesting that ASHS-OAP is a viable alternative to current manual segmentation methods for detecting group differences based on cognitive status. Although ASHS-OAP and ASHS-PMC produced varying volumes for most regions of interest, they both identified early signs of neurodegeneration in CA2/CA3/DG and identified marginal differences in entorhinal cortex. Our findings highlight the utility of automated segmentation methods but still underscore the need for a unified and harmonized MTL segmentation atlas.

Study objectivesInsomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network, and central executive network (CEN).MethodsWe selected 320 participants from the ADNI database and divided them by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores.ResultsInsomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterized by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were nonsignificant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD.ConclusionsWe conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

BACKGROUND: People living with HIV experience HIV stigma alongside a spectrum of aging-related health conditions that accelerate their vulnerability to the ill effects of loneliness and social isolation. Group-singing interventions are efficacious in improving psychosocial well-being among older people in the general population; however, the social curative effects of group singing have not been explored in relation to HIV stigma. By promoting group identification, bonding, and pride, group singing may reduce loneliness, social isolation, and other negative impacts of HIV stigma among older people living with HIV. Access to group-singing programs may be enhanced by technology. OBJECTIVE: While group singing has been extensively studied in older adults, group-singing interventions have not been adapted for older people living with HIV to target loneliness and social isolation in the context of HIV stigma. The objective of this study was to describe the systematic development of a group-singing intervention to reduce loneliness and social isolation among older people living with HIV. METHODS: In the San Francisco Bay Area between February 2019 and October 2019, we engaged older people living with HIV in a rigorous, 8-stage, community-engaged intervention adaptation process using the Assessment, Decision, Adaptation, Production, Topical Experts, Integration, Training, and Testing (ADAPT-ITT) framework. On the basis of a formative assessment of the needs and preferences of older people living with HIV, we selected an evidence-based group-singing intervention for older adults and systematically adapted the intervention components by administering them to a community advisory council (n=13). RESULTS: The result was United Voices, a 12-week hybrid (web-based and in-person) group-singing intervention for older people living with HIV. United Voices comprises 12 web-based (ie, via Zoom [Zoom Video Communications]) rehearsals, web-based and in-person drop-in helpdesk sessions, and a professionally produced final concert recording. CONCLUSIONS: Through an iterative process and in consultation with stakeholders and topic experts, we refined and manualized United Voices and finalized the design of a pilot randomized controlled trial to evaluate the feasibility and acceptability of the intervention protocol and procedures. The findings provide insights into the barriers and facilitators involved in culturally tailoring interventions for older people living with HIV, implementing intervention adaptations within web-based environments, and the promise of developing hybrid music-based interventions for older adults with HIV.

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample size. These efforts unveil new questions about how to integrate data across distinct sources and instruments. The goal of this study was to link scores across common auditory verbal learning tasks (AVLTs). This international secondary analysis aggregated multisite raw data for AVLTs across 53 studies totaling 10,505 individuals. Using the ComBat-GAM algorithm, we isolated and removed the component of memory scores associated with site effects while preserving instrumental effects. After adjustment, a continuous item response theory model used multiple memory items of varying difficulty to estimate each individual's latent verbal learning ability on a single scale. Equivalent raw scores across AVLTs were then found by linking individuals through the ability scale. Harmonization reduced total cross-site score variance by 37% while preserving meaningful memory effects. Age had the largest impact on scores overall (- 11.4%), while race/ethnicity variable was not significant (p > 0.05). The resulting tools were validated on dually administered tests. The conversion tool is available online so researchers and clinicians can convert memory scores across instruments. This work demonstrates that global harmonization initiatives can address reproducibility challenges across the behavioral sciences.

PurposeWe aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature.MethodsData obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms.ResultsThere were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively.ConclusionWe observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition.

Memory for temporal structure enables both planning of future events and retrospection of past events. We investigated how the brain flexibly represents extended temporal sequences into the past and future during anticipation. Participants learned sequences of environments in immersive virtual reality. Pairs of sequences had the same environments in a different order, enabling context-specific learning. During fMRI, participants anticipated upcoming environments multiple steps into the future in a given sequence. Temporal structure was represented in the hippocampus and across higher-order visual regions (1) bidirectionally, with graded representations into the past and future and (2) hierarchically, with further events into the past and future represented in successively more anterior brain regions. In hippocampus, these bidirectional representations were context-specific, and suppression of far-away environments predicted response time costs in anticipation. Together, this work sheds light on how we flexibly represent sequential structure to enable planning over multiple timescales.

BackgroundDespite elevated rates of trauma exposure, substance misuse, mental health problems, and suicide, systems-impacted teens and their caregivers have limited access to empirically supported behavioral health services. Family-based interventions are the most effective for improving mental health, education, substance use, and delinquency outcomes, yet the familial and placement disruption that occurs during child welfare involvement can interfere with the delivery of family-based interventions.ObjectiveTo address this gap in access to services, we adapted an in-person, empirically supported, family-based affect management intervention using a trauma-informed lens to be delivered via telehealth to families impacted by the child welfare system (Family Telehealth Project). We describe the intervention adaptation process and an open trial to evaluate its feasibility, acceptability, and impact.MethodsAdaptations to the in-person, family-based affect management intervention were conducted iteratively with input from youth, caregivers, and systems partners. Through focus groups and collaborative meetings with systems partners, a caregiver-only version of the intervention was also developed. An open trial of the intervention was conducted to assess family perspectives of its acceptability and feasibility and inform further refinements prior to a larger-scale evaluation. Participants included English-speaking families involved in the child welfare system in the past 12 months with teens (aged 12-18 years). Caregivers were eligible to participate either individually (caregivers of origin, kinship caregivers, or foster parents; n=7) or with their teen (caregiver of origin only; n=6 dyads). Participants completed session feedback forms and surveys at pretreatment, posttreatment, and 3-month posttreatment time points. Qualitative exit interviews were conducted with a subset of participants (12/19, 63%) to further understand their experiences with the intervention.ResultsSession attendance was high, and both caregivers and teens reported high acceptability of clinicians and sessions on feedback forms. Families were comfortable with video technology, with very few (

Youth Mental Health First Aid (YMHFA) trains individuals who regularly interact with youth to identify youth experiencing mental health challenges. Several studies demonstrate positive training impacts, but few assess whether the training equally impacts participants of different demographic and professional backgrounds or those who participate in different training modalities. Using a pre-post follow-up design with a comparison group, this study examined changes in participants confidence in their ability to recognize and support youth mental health needs 1 to 2 months after training. Data were collected over two years (2021-2023) from training participants (n = 480) and comparable non-participants (n = 51). The authors examined whether changes in confidence varied by participant race/ethnicity, professional role in the education or mental health fields, and training modality (online versus hybrid). Training participants confidence in supporting youth mental health increased significantly compared to non-participants. Although the training was effective for all participants, those with less mental health experience benefited more, consistent with previous research. While both in-person and hybrid training were effective, in-person training participants reported slightly higher confidence scores than virtual at follow-up. Study findings suggest that educational and social service organizations should offer this training to their staff and community members who interact with youth, prioritizing participants with less prior mental health training and delivering training through an in-person training modality when possible. However, additional research is needed to explore how aspects of in-person training, such as trainer characteristics and group dynamics, impact outcomes.

The fundamental organization of the human brain is established before birth, with rapid growth continuing over the first postnatal years. Children exposed before or after birth to various biological (e.g., substance exposure) or psychosocial hazards (e.g., maltreatment) are at elevated likelihood of deviating from a typical developmental trajectory, which in turn can be associated with psychological, behavioral, and physical health sequelae. In the HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, brain, physical, biological, cognitive, behavioral, social, and emotional development is being examined starting in pregnancy and planned through age 10 (data are sampled at varying degrees of granularity depending on age, with more dense sampling earlier in life). HBCD aims to determine the short- and long-term impacts of a variety of both harmful and protective factors, including prenatal substance use, on developmental trajectories through early childhood. Organized as a nationwide consortium across 27 sites, the HBCD Study will collect multimodal data that will be made publicly available on a yearly basis, through a data use application and approval process. Here we provide an overview of the HBCD Study design, sampling, protocol development, and data management. Data collected through HBCD will be fundamental to informing future prenatal and early childhood interventions and policies to promote wellbeing and resilience in all children.

Child abuse has intergenerational consequences for psychopathology, however, there remains a paucity of research regarding how these experiences affect Latinx families, particularly those at risk for additional negative life events, such as racial discrimination. This study aims to contribute to this gap in the literature by examining the impact maternal child abuse exposure has on youth and maternal psychopathology, as well as whether these associations are moderated by racial discrimination, in a sample of 224 Latinx mother-youth dyads. Hierarchical regressions revealed small but significant maternal child abuse exposure x racial discrimination interactions for youth depression and anxiety, but not maternal depression or anxiety, which were solely positively associated with maternal child abuse exposure. Findings highlight the multifarious, and at times convergent, nature of trauma and oppression among Latinx families, as well as the impact across generations. Future work is needed to further elucidate developmental pathways of intergenerational trauma in understudied populations.

PurposeTraumatic brain injury (TBI) and potentially traumatic events (PTEs) contribute to increased substance use, mental health issues, and cognitive impairments. However, there's not enough research on how TBI and PTEs combined impact mental heath, substance use, and neurocognition.MethodsThis study leverages a subset of The National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) multi-site dataset with 551 adolescents to assess the combined and distinctive impacts of TBI, PTEs, and TBI+PTEs (prior to age 18) on substance use, mental health, and neurocognitive outcomes at age 18.ResultsTBI, PTEs, and TBI+PTEs predicted greater lifetime substance use and past-year alcohol and cannabis use. PTEs predicted greater internalizing symptoms, while TBI+PTEs predicted greater externalizing symptoms. Varying effects on neurocognitive outcomes included PTEs influencing attention accuracy and TBI+PTEs predicting faster speed in emotion tasks. PTEs predicted greater accuracy in abstraction-related tasks. Associations with working memory were not detected.ConclusionThis exploratory study contributes to the growing literature on the complex interplay between TBI, PTEs, and adolescent mental health, substance use, and neurocognition. The developmental implications of trauma via TBIs and/or PTEs during adolescence are considerable and worthy of further investigation.

Although stress is often related to substance use, it remains unclear whether substance use is related to individual differences in how adolescents respond to stress. Therefore the present study examined associations between substance use and daily emotional reactivity to stress within a year across adolescence. Adolescents (N = 330; Mage = 16.40, SD = 0.74 at study entry; n = 186 female; n = 138 Latine; n = 101 European American; n = 72 Asian American; n = 19 identifying as another ethnicity including African American and Middle Eastern) completed a longitudinal study, including three assessments between the 10th grade and 3-years post-high school. At each assessment, participants reported frequency of alcohol and cannabis use and the number of substances they had ever used. They also completed 15 daily checklists, in which they reported the number of daily arguments and their daily emotion. Multilevel models suggested that more frequent alcohol and cannabis use were related to attenuated positive emotional reactivity to daily stress (i.e., smaller declines in positive emotion on days when they experienced more arguments) for both male and female adolescents. Associations for negative emotional reactivity to stress varied by sex; more frequent alcohol use and use of more substances in one's lifetime were related to greater anxious emotional reactivity to stress among female adolescents, whereas more frequent alcohol and cannabis use and higher lifetime substance use were related to attenuated depressive emotional reactivity to stress among male adolescents. Taken together, substance use was related to emotional reactivity to daily stress within the same year during adolescence, although associations differed by valence and adolescent sex.