The Hierarchical Taxonomy of Psychopathology (HiTOP) and Research Domain Criteria (RDoC) frameworks emphasize transdiagnostic and mechanistic aspects of psychopathology. We used a multi-omics approach to examine how HiTOP’s psychopathology spectra (externalizing [EXT], internalizing [INT], and shared EXT + INT) map onto RDoC’s units of analysis.

We conducted analyses across five RDoC units of analysis: genes, molecules, cells, circuits, and physiology. Using genome-wide association studies from the companion Part I article, we identified genes and tissue-specific expression patterns. We used drug repurposing analyses that integrate gene annotations to identify potential therapeutic targets and single-cell RNA sequencing data to implicate brain cell types. We then used magnetic resonance imaging data to examine brain regions and circuits associated with psychopathology. Finally, we tested causal relationships between each spectrum and physical health conditions.

Using five gene identification methods, EXT was associated with 1,759 genes, INT with 454 genes, and EXT + INT with 1,138 genes. Drug repurposing analyses identified potential therapeutic targets, including those that affect dopamine and serotonin pathways. Expression of EXT genes was enriched in GABAergic, cortical, and hippocampal neurons, while INT genes were more narrowly linked to GABAergic neurons. EXT + INT liability was associated with reduced gray matter volume in the amygdala and subcallosal cortex. INT genetic liability showed stronger causal effects on physical health – including chronic pain and cardiovascular diseases – than EXT.

Our findings revealed shared and distinct pathways underlying psychopathology. Integrating genomic insights with the RDoC and HiTOP frameworks advanced our understanding of mechanisms that underlie EXT and INT psychopathology.

There is considerable comorbidity between externalizing (EXT) and internalizing (INT) psychopathology. Understanding the shared genetic underpinnings of these spectra is crucial for advancing knowledge of their biological bases and informing empirical models like the Research Domain Criteria (RDoC) and Hierarchical Taxonomy of Psychopathology (HiTOP).

We applied genomic structural equation modeling to summary statistics from 16 EXT and INT traits in individuals genetically similar to European reference panels (EUR-like; n = 16,400 to 1,074,629). Traits included clinical (e.g. major depressive disorder, alcohol use disorder) and subclinical measures (e.g. risk tolerance, irritability). We tested five confirmatory factor models to identify the best fitting and most parsimonious genetic architecture and then conducted multivariate genome-wide association studies (GWAS) of the resulting latent factors.

A two-factor correlated model, representing EXT and INT spectra, provided the best fit to the data. There was a moderate genetic correlation between EXT and INT (r = 0.37, SE = 0.02), with bivariate causal mixture models showing extensive overlap in causal variants across the two spectra (94.64%, SE = 3.27). Multivariate GWAS identified 409 lead genetic variants for EXT, 85 for INT, and 256 for the shared traits.

The shared genetic liabilities for EXT and INT identified here help to characterize the genetic architecture underlying these frequently comorbid forms of psychopathology. The findings provide a framework for future research aimed at understanding the shared and distinct biological mechanisms underlying psychopathology, which will help to refine psychiatric classification systems and potentially inform treatment approaches.

Genetic and environmental factors, including adverse childhood experiences (ACEs), contribute to substance use disorders (SUDs). However, the interactions between these factors are poorly understood.

We examined associations between SUD polygenic scores (PGSs), ACEs, and the initiation of use and severity of alcohol (AUD), opioid use disorder (OUD), and cannabis use disorder (CanUD) in 10,275 individuals (43.5% female, 47.2% African-like ancestry [AFR], and 52.8% European-like ancestry [EUR]). ACEs and SUD severity were modeled as latent factors. We conducted logistic and linear regressions within ancestry groups to examine the associations of ACEs, PGS, and their interaction with substance use initiation and SUD severity.

All three SUD PGS were associated with ACEs in EUR individuals, indicating a gene–environment correlation. Among EUR individuals, only the CanUD PGS was associated with initiating use, whereas ACEs were associated with initiating use of all three substances in both ancestry groups. Additionally, a negative gene-by-environment interaction was identified for opioid initiation in EUR individuals. ACEs were associated with all three SUD severity latent factors in EUR individuals and with AUD and CanUD severity in AFR individuals. PGS were associated with AUD severity in both ancestry groups and with CanUD severity in AFR individuals. Gene-by-environment interactions were identified for AUD and CanUD severity among EUR individuals.

Findings highlight the roles of ACEs and polygenic risk in substance use initiation and SUD severity. Gene-by-environment interactions implicate ACEs as moderators of genetic susceptibility, reinforcing the importance of considering both genetic and environmental influences on SUD risk.

To examine the risk of perinatal mental illness, including new diagnoses and recurrent use of mental healthcare, comparing women with and without traumatic brain injury (TBI), and to identify injury-related factors associated with these outcomes among women with TBI.

We conducted a population-based cohort study in Ontario, Canada, of all obstetrical deliveries to women in 2012–2021, excluding those with mental healthcare use in the year before conception. The cohort was stratified into women with no remote mental illness history (to identify new mental illness diagnoses between conception and 365 days postpartum) and those with a remote mental illness history (to identify recurrent illnesses). Modified Poisson regression generated adjusted relative risks (aRRs) (1) comparing women with and without TBI and (2) according to injury-related variables (i.e., number, severity, timing, mechanism and intent) among women with TBI.

There were n = 12,724 women with a history of TBI (mean age: 27.6 years [SD, 5.5]) and n = 786,317 without a history of TBI (mean age: 30.6 years [SD, 5.0]). Women with TBI were at elevated risk of a new mental illness diagnosis in the perinatal period compared to women without TBI (18.5% vs. 12.7%; aRR: 1.31, 95% confidence interval [CI]: 1.24–1.39), including mood and anxiety disorders. Women with a TBI were also at elevated risk for recurrent use of mental healthcare perinatally (35.5% vs. 27.8%; aRR: 1.18, 95% CI: 1.14–1.22), including mood and anxiety, psychotic, substance use and other mental health disorders. Among women with a history of TBI, the number of TBI-related healthcare encounters was positively associated with an elevated risk of new-onset mental illness.

These findings demonstrate the need for providers to be attentive to the risk for perinatal mental illness in women with a TBI. This population may benefit from screening and tailored mental health supports and treatment options.

Although typically serving higher income and younger demographic groups, meal-kit subscription services have the potential to improve food availability and dietary quality in communities experiencing low food access due to systemic discrimination. This study describes the development and characteristics of a pilot community-led meal-kit service (SouthEats) and evaluates key implementation outcomes of adoption, acceptability, and feasibility among households experiencing less income.

We utilised a mixed methods study design, including data from administrative records, customer surveys and worker interviews. Thematic qualitative analyses and descriptive quantitative analyses were conducted to illuminate the characteristics and extent the pilot meal-kit service was adopted, acceptable, and financially feasible among the target populations.

The study took place in Washington DC, USA.

Study participants included SouthEats consumers (n 35) and workers (n 3).

During the pilot period, sixty-seven community members signed up for the meal-kit service, with 52 % making recurring purchases. Our results suggest that the meal-kit service is acceptable among people living in low food access areas. Our feasibility analysis indicates that, although not without challenges, the SouthEats model could be financially feasible.

These preliminary insights can inform the scalability and potential replication of this service and provide foundational evidence for an approach that may be used to improve food access.

Previous research has explored the performance of working memory in children with ADHD and individual co-occurring disorders, finding that internalizing disorders such as depression and anxiety, both independently negatively impact working memory performance (Saarinen, Fontell, Vuontela, Carlson, & Aronen, 2015; Kofler, Rapport, Bolden, Sarver, Raiker, & Alderson, 2011; Skogan, Zeiner, Egeland, Rohrer-Baumgartner, Urnes, Reichborn-Kjennerud & Aase, 2013). However, there is limited research on the impact of co-occurring depression and anxiety on working memory, which are common in children with ADHD. When depression is present, parts of the prefrontal cortex regions are hypoactive and therefore lead to impairment in executive functioning abilities (Snyder, 2013). In regard to anxiety, previous literature (Moran, 2016) has found that anxious arousal competes with processes located in the prefrontal cortex leaving limited neural resources for executive functioning skills (Moran, 2016). The current study will evaluate the influences of depression and anxiety on working memory in children with ADHD.

Participants were from an archived data set, which included 849 individual children ages 7-15 years old and their biological parents, recruited between 2009 and 2015. The 849 children included 76 sibling pairs. Families were part of an ongoing longitudinal study. The children completed a computerized version of a spatial working memory task identical to the spatial span task from CANTAB (De Luca et al., 2003). In regard to verbal working memory, children completed Digit Span from the WISC-IV, including both forward and backward conditions. Depression was measured by the Children’s Depression Inventory, 2nd edition (Kovac, 2004) and anxiety was measured by the Multidimensional Anxiety Scale for Children, 2nd edition (MASC-2) (March, 2012). ADHD was measured by having the parents and teachers complete two questionnaires: the ADHD rating scale (ADHD-RS; DuPaul et al. 1998), the Connor’s Rating Scale, 3rd edition (CRS-R, Connors 2003), and an in person semi-structured diagnostic interview (Kiddie Schedule for Affective Disorders and Schizophrenia -KSADS, Kaufman et al. 1997). A best estimate DSM-IV ADHD (American Psychiatric Association [APA], 1994) diagnosis was established by a multidisciplinary diagnostic team (ADHD diagnosis agreement kappa = .88). On cases where consensus was not achieved, they were excluded from the participant pool, and this became the clinical referred control group for the study.

The results indicated that children with ADHD and a co-occurring diagnosis of depression experience more difficulties with working memory abilities than those who do not have a co-occurring diagnosis of depression. Additionally, depression has a greater impact on verbal working memory in children with ADHD than anxiety does alone. This study also found that there were no significant gender differences between children with ADHD who identify as males and females on verbal or visual working memory tasks.

The findings of this study indicate the importance of addressing depressive symptoms in children with ADHD. With a holistic understanding of working memory deficits in children with ADHD as well as potential gender differences, caretakers and providers can integrate more effective intervention plans to help mitigate significant working memory deficits.

The purpose of this scoping review is two-fold: to assess the literature that quantitatively measures outcomes of mentorship programs designed to support research-focused junior faculty and to identify mentoring strategies that promote diversity within academic medicine mentoring programs.

Studies were identified by searching Medline using MESH terms for mentoring and academic medicine. Eligibility criteria included studies focused on junior faculty in research-focused positions, receiving mentorship, in an academic medical center in the USA, with outcomes collected to measure career success (career trajectory, career satisfaction, quality of life, research productivity, leadership positions). Data were abstracted using a standardized data collection form, and best practices were summarized.

Search terms resulted in 1,842 articles for title and abstract review, with 27 manuscripts meeting inclusion criteria. Two studies focused specifically on women, and four studies focused on junior faculty from racial/ethnic backgrounds underrepresented in medicine. From the initial search, few studies were designed to specifically increase diversity or capture outcomes relevant to promotion within academic medicine. Of those which did, most studies captured the impact on research productivity and career satisfaction. Traditional one-on-one mentorship, structured peer mentorship facilitated by a senior mentor, and peer mentorship in combination with one-on-one mentorship were found to be effective strategies to facilitate research productivity.

Efforts are needed at the mentee, mentor, and institutional level to provide mentorship to diverse junior faculty on research competencies and career trajectory, create a sense of belonging, and connect junior faculty with institutional resources to support career success.

Diversity, equity, and inclusion (DEI) in clinical and translational science (CTS) are paramount to driving innovation and increasing health equity. One important area for improving diversity is among trainees in CTS programs. This paper reports on findings from a special session at the November 2020 Clinical and Translational Science Award (CTSA) national program meeting that focused on advancing diversity and inclusion within CTS training programs.

Using qualitative content analysis, we identified approaches brought forth to increase DEI in KL2 career development and other training programs aimed at early-stage CTS investigators, beyond the six strategies put forth to guide the breakout session (prioritizing representation, building partnerships, making it personal, designing program structure, improving through feedback, and winning endorsement). We used an inductive qualitative content analysis approach to identify themes from a transcript of the panel of KL2 program leaders centered on DEI in training programs.

We identified four themes for advancing DEI within CTS training programs: 1) institutional buy-in; 2) proactive recruitment efforts; 3) an equitable application process; and 4) high-quality, diverse mentorship.

Implementing these strategies in CTS and other training programs will be an important step for advancing DEI. However, processes need to be established to evaluate the implementation and effectiveness of these strategies through continuous quality improvement, a key component of the CTSA program. Training programs within the CTSA are well-positioned to be leaders in this critical effort to increase the diversity of the scientific workforce.

To design a meditation protocol and test its feasibility, acceptability and efficacy in conjunction with yoga training (YT) for persons with schizophrenia (SZ).

The meditation protocol consisted of Anapana (observing normal respiration) and Yoga Nidra (supine, restful awareness). In a single-blind randomised controlled trial, medicated and clinically stable outpatients diagnosed with SZ were randomised to receive treatment as usual (TAU), TAU augmented with YT or TAU augmented with meditation and yoga training (MYT) for 3 weeks (N = 145). Acceptability, clinical, social and cognitive functions were assessed after 3-week and 3-month post-randomisation using within-group and between-group analyses with repeated measures multivariate tests.

No group-wise differences in compliance, study discontinuation, major/serious side effects or adverse events were noted. For six assessed clinical variables, the direction of changes were in the desired direction and the effect sizes were greater in the MYT group compared with the TAU group at both time points. Changes in social function variables were greater at 3 months than at 3 weeks. Nominally significant improvement in individual cognitive domains were noted in all groups at both time points. All effect sizes were in the small to medium range.

MYT is feasible and acceptable and shows modest benefits for persons with SZ. MYT can also improve quality of life and clinical symptoms. Larger studies of longer duration are warranted.

In March 2020, New York City became the epicenter of the coronavirus disease 2019 (COVID-19) pandemic in the United States. Because healthcare facilities were overwhelmed with patients, the Jacob K. Javits Convention Center was transformed into the nation’s largest alternate care site: Javits New York Medical Station (hereafter termed Javits). Protecting healthcare workers (HCWs) during a global shortage of personal protective equipment (PPE) in a nontraditional healthcare setting posed unique challenges. We describe components of the HCW safety program implemented at Javits.

Javits, a large convention center transformed into a field hospital, with clinical staff from the US Public Health Service Commissioned Corps and the US Department of Defense.

Key strategies to ensure HCW safety included ensuring 1-way flow of traffic on and off the patient floor, developing a matrix detailing PPE required for each work activity and location, PPE extended use and reuse protocols, personnel training, and monitoring adherence to PPE donning/doffing protocols when entering or exiting the patient floor. Javits staff who reported COVID-19 symptoms were immediately isolated, monitored, and offered a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) test.

A well-designed and implemented HCW safety plan can minimize the risk of SARS-CoV-2 infection for HCWs. The lessons learned from operating the nation’s largest COVID-19 alternate care site can be adapted to other environments during public health emergencies.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.