Antipsychotic (AP) medication in individuals at clinical high risk for psychosis (CHR-P) is not routinely recommended by clinical guidelines but is commonly prescribed. Since little is known about the predictors of AP inception in CHR-P, we analyzed data from two observational cohorts.

To avoid baseline predictors being confounded by previous treatment, participants were selected for analysis from the 764 participants at CHR-P enrolled in NAPLS-2 and the 710 enrolled in NAPLS-3 by excluding those with lifetime histories of AP use. Baseline clinical variables available in both studies were employed as predictors of subsequent AP inception over the next 6 months in univariable and multivariable analyses.

Preliminary analyses indicated no important effects of sample. The final combined population included 79 AP inception participants and 580 participants who did not have AP inception. The AP medications most commonly prescribed were risperidone, aripiprazole, and quetiapine. Univariable analyses identified seven significant predictors of AP inception. The final logistic regression model including these variables was highly significant (χ2 = 36.53, df = 7, p = <0.001). Three variables (current major depression, fewer education years, and current benzodiazepine use) emerged as significant independent predictors of AP inception.

This study is the first to determine baseline characteristics that predict subsequent AP initiation in CHR-P. Some AP use in CHR-P appears to be intended as augmentation of antidepressant treatment for comorbid major depression. Some prescribers may not have detected the attenuated positive symptoms characteristic of CHR-P since their severity did not significantly predict AP inception.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.

This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.

Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.

The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.

This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.

Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.

Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.

Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021.

CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively.

Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles.

To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.

Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Late Life Major Depressive Disorder (LLD) and Hoarding Disorder (HD) are common in older adults with prevalence estimates up to 29% and 7%, respectively. Both LLD and HD are characterized by executive dysfunction and disability. There is evidence of overlapping neurobiological dysfunction in LLD and HD suggesting potential for compounded executive dysfunction and disability in the context of comorbid HD and LLD. Yet, prevalence of HD in primary presenting LLD has not been examined and potential compounded impact on executive functioning, disability, and treatment response remains unknown. Thus, the present study aimed to determine the prevalence of co-occurring HD in primary presenting LLD and examine hoarding symptom severity as a contributor to executive dysfunction, disability, and response to treatment for LLD.

Eighty-three adults ages 65-90 participating in a psychotherapy study for LLD completed measures of hoarding symptom severity (Savings Inventory-Revised: SI-R), executive functioning (WAIS-IV Digit Span, Letter-Number Sequencing, Coding; Stroop Interference; Trail Making Test-Part B; Letter Fluency), functional ability (World Health Organization Disability Assessment Schedule-II-Short), and depression severity (Hamilton Depression Rating Scale) at post-treatment. Pearson's Chi-squared tests evaluated group differences in cognitive and functional impairment rates and depression treatment response between participants with (HD+LLD) and without (LLD-only) clinically significant hoarding symptoms. Linear regressions were used to examine the association between hoarding symptom severity and executive function performance and functional ability and included as covariates participant age, years of education, gender, and concurrent depression severity.

At post-treatment, 24.1% (20/83) of participants with LLD met criteria for clinically significant hoarding symptoms (SI-R.41). Relative to LLD-only, the LLD+HD group demonstrated greater impairment rates in Letter-Number Sequencing (χ2(1)=4.0, p=.045) and Stroop Interference (χ2(1)=4.8, p=.028). Greater hoarding symptom severity was associated with poorer executive functioning performance on Digit Span (t(71)=-2.4, β=-0.07, p=.019), Letter-Number Sequencing (t(70)=-2.1, β=-0.05, p=.044), and Letter Fluency (t(71)=-2.8, β=-0.24, p=.006). Rates of functional impairment were significantly higher in the LLD+HD (88.0%) group compared to the LLD-only (62.3%) group, (χ2(1)=5.41, p=.020). Additionally, higher hoarding symptom severity was related to greater disability (t(72)=2.97, β=0.13, p=.004). Furthermore, depression treatment response rates were significantly lower in the LLD+HD group at 24.0% (6/25) compared to 48.3% (28/58) in the LLD-only group, χ2(1)=4.26, p=.039.

The present study is among the first to report prevalence of clinically significant hoarding symptoms in primary presenting LLD. The findings of 24.1% co-occurrence of HD in primary presenting LLD and increased burden on executive functioning, disability, and depression treatment outcomes have important implications for intervention and prevention efforts. Hoarding symptoms are likely under-evaluated, and thus may be overlooked, in clinical settings where LLD is identified as the primary diagnosis. Taken together with results indicating poorer depression treatment response in LLD+HD, these findings underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group. Future work examining the course of hoarding symptomatology in LLD (e.g., onset age of hoarding behaviors) may provide insights into the mechanisms associated with greater executive dysfunction and disability.