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.

To examine the proportion of products offered by leading food brands in Canada that are ‘unhealthy’ according to Health Canada’s (HC) nutrient profile model for proposed restrictions on food marketing to children (M2K-NPM).

Nutritional information for products offered by top brands was sourced from the University of Toronto FLIP and Menu-FLIP 2020 databases, respectively. HC’s M2K-NPM, which includes thresholds for Na, total sugars and saturated fat, was applied to products.

Canada.

Overall, 1385 products from top breakfast cereal (n 15 brands, n 222 products), beverage (n 21 brands, n 769 products) and yogurt (n 10 brands, n 394 products) brands, and 3153 menu items from seventeen chain restaurants in Canada were assessed (n 60 unique brands overall).

For 42 % of brands (n 21), 100 % of their products exceeded ≥1 nutrient threshold(s), with ≥50 % of the products offered by twenty-three brands (46 %) exceeding two thresholds. Specifically, one or more nutrient thresholds were exceeded by ≥50 % of the products offered by 14/15 breakfast cereal brands, 18/21 beverage brands, all ten yogurt brands and all seventeen restaurant brands. Notably, 100·0 % of the products offered by ten breakfast cereal, six beverage, two yogurt and three restaurant brands exceeded ≥1 threshold(s).

Most products offered by top food brands in Canada exceeded HC’s M2K-NPM thresholds. Nonetheless, these brands could still be marketed under the proposed regulations, which exclude brand marketing (i.e. promotions without an identifiable product) despite its contribution to marketing power. These findings reinforce the need for Canada and other countries to include brand marketing in M2K policies.

Childhood sexual abuse (CSA) and emotional maltreatment are salient risk factors for the development of major depressive disorder (MDD) in women. However, the type- and timing-specific effects of emotional maltreatment experienced during adolescence on future depressive symptomatology in women with CSA have not been explored. The goal of this study was to fill this gap.

In total, 203 women (ages 20–32) with current depressive symptoms and CSA (MDD/CSA), remitted depressive symptoms and CSA (rMDD/CSA), and current depressive symptoms without CSA (MDD/no CSA) were recruited from the community and completed self-report measures. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II) and a detailed maltreatment history was collected using the Maltreatment and Abuse Chronology of Exposure (MACE). Differences in maltreatment exposure characteristics, including multiplicity and severity of maltreatment, as well as the chronologies of emotional maltreatment subtypes were compared among groups. A random forest machine-learning algorithm was utilized to assess the impact of exposure to emotional maltreatment subtypes at specific ages on current depressive symptoms.

MDD/CSA women reported greater prevalence and severity of emotional maltreatment relative to rMDD/CSA and MDD/no CSA women [F(2,196) = 9.33, p < 0.001], specifically from ages 12 to 18. The strongest predictor of current depressive symptoms was parental verbal abuse at age 18 for both MDD/CSA women (variable importance [VI] = 1.08, p = 0.006) and MDD/no CSA women (VI = 0.68, p = 0.004).

Targeting emotional maltreatment during late adolescence might prove beneficial for future intervention efforts for MDD following CSA.

This study examined the relationship between reformulation and food price in Canadian packaged foods and beverages between 2017 and 2020.

Matched foods and beverages in the University of Toronto Food Label Information and Price 2017 and 2020 databases were analysed (n 5774). Price change by food category and by retailer were compared using Wilcoxon signed-rank tests. The proportion of products with changes in calories and nutrient levels were determined, and mixed-effects models were used to examine the relationship between reformulation and price changes. The Food Standards Australia New Zealand (FSANZ) nutrient profiling model was applied to calculate nutritional quality scores, and mixed-effects models were used to assess if changes in nutritional quality score were associated with price changes.

Large grocery retailers by market share in Canada.

Foods and beverages available in 2017 and 2020.

Food price changes differed by retailer and by food category (e.g. increased in Bakery, Snacks, etc; decreased in Beverages, Miscellaneous, etc.). Nutrient reformulation was minimal and bidirectional with the highest proportion of products changing in sodium (17·8 %; 8·4 % increased and 9·4 % decreased). The relationship between nutrient reformulation and price change was insignificant for all nutrients overall and was not consistent across food categories. Average FSANZ score did not change (7·5 in both years). For Legumes and Combination dishes, improvements in nutritional quality were associated with a price decrease and increase, respectively.

Stronger policies are required to incentivise reformulation in Canada. Results do not provide evidence of reformulation impacting food prices.

The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed.

Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted.

Six thematic challenges including infection control considerations, the interplay between provision of clinical care and research, competing clinical trials, arduous consenting procedures, onerous procedural requirements, and participant recruitment including achieving representation of diverse populations were identified and are discussed here.

Consideration of the lessons learned and recommendation outlined here may allow for more efficient conduct of inpatient clinical trials in future pandemics.

The concept of digital psychiatry, encompassing technologies such as mental health apps, Virtual Reality (VR), Artificial Intelligence (AI), and telepsychiatry, emerges as a potential solution to bridge the existing gaps in the mental health system of Pakistan. However, one of the major barriers to the implementation of these technologies is hesitancy to adopt digital tools by psychiatrists.

This study aims to explore the current understanding of digital psychiatry, the barriers faced by psychiatrists in its’ widespread implementation, and their willingness to adopt these services in clinical practice.

This cross-sectional study surveyed psychiatrists’ knowledge, attitudes, and practices on digital psychiatry from 39 public hospitals across Pakistan using an online validated questionnaire from January to July 2023. Participants included psychiatry residents, fellows, and consultants practicing in Pakistan. Responses were analyzed with Raosoft software, Quirkos, and SPSS 26 using thematic analysis and correlation.

A total of 200 participants responded to the questionnaire, primarily in the age range of 20-30 years (56%). The gender distribution was 55% male (N = 111) and 45% female (N = 89). Among the professional roles, 23% were consultants, 7% were registrars, 54% were psychiatry residents, and 17% were medical officers. Respondents came from both rural (N = 148, 74%) and urban (N = 52, 26%) practice settings. Regarding telepsychiatry, 46% strongly agreed that they are familiar with telepsychiatry, while 58% agreed that telepsychiatry can save time and money. Additionally, 22% strongly agreed that it’s a viable approach for patient care. Concerning perspectives on Artificial Intelligence (AI) in digital psychiatry readiness, only 40% of participants had received AI training. However, 55% expressed interest in collaborating with international centers on AI-related projects. In terms of mental health apps, 62% of respondents reported limited familiarity with them. Nevertheless, 65% believed that these apps could potentially save time and money for psychiatric health systems. Lastly, concerning Virtual Reality (VR) in psychiatric care, 57% of participants were familiar with VR technology, but only 43% were acquainted with its applications in psychiatry. Notably, 71% did not view VR as a viable replacement for in-person psychiatric management.

This is the first study conducted on understanding digital psychiatry in Pakistan’s healthcare system, which revealed multiple challenges to digital health competency among psychiatrists. This emphasizes on the need for formal training and funding towards resources to overcome obstacles in utilizing mental health technologies.

None Declared

The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist.

This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants.

Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013).

The study results suggest that exposure to the subcutaneous route influences a physician’s perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Victims of electrical injury (EI) often experience injuries to the peripheral nervous system and neuromuscular damage that may diminish motor function, such as flexibility/dexterity. These difficulties may continue after rehabilitation due to the reorganization of muscle afferent projections during peripheral nerve regeneration. Therefore, understanding how patients with a history of thermal burn injuries perform on motoric measures is necessary to explain the impact neuromuscular damage has on both motor and non-motor tests of cognition. However, no studies have examined the impact of motor functioning on cognition in patients who experienced thermal and electrical injuries compared to an electrical shock injury. This study explored the impact of motor dysfunction and psychiatric distress measured by depression severity on psychomotor speed and executive test performances among EI patients with and without thermal burn injuries.

This cross-sectional study consisted of EI patients undergoing an outpatient neuropsychological evaluation, including tests of motor dexterity (Grooved Pegboard [GP]), psychomotor speed (Wechsler Adult Intelligence Scale-IV Coding, Trail Making Test [TMT] Part A), and executive functioning (Stroop Color and Word Test [SCWT] Color-Word trial, TMT Part B). The sample was 83% male and 17% female, 88% White, 3% Black, 5% Hispanic, and 2% other race/ethnicity, with a mean age of 43.9 years (SD=11.36), mean education of 12.9 years (SD=2.05), and mean depression severity of 20.05 (SD=12.59) on the Beck Depression Inventory-II (BDI-II). Exclusion criteria were: 1) injury history of moderate-to-severe head trauma, 2) >2 performance validity test failures, and 3) any amputation of the upper extremity. Regression analyses included GP T-Scores for dominant hand and BDI-II total score as independent variables and neuropsychological normative test data as dependent variables.

Among validly performing patients with EI (n=86), regression analyses revealed GP performance accounted for significant variance (R2 =.153-.169) on all neuropsychological measures. Among EI patients with burn injuries (n=50), regression analyses revealed GP performance accounted for significant variance (R2 =.197-.266) on all neuropsychological measures. Among EI patients without burn injuries (n=36), analyses revealed that neither GP performance nor BDI-II severity accounted for significant variance across the neurocognitive tests (R2=.056-.142). Furthermore, among EI patients with burn injuries and the total sample, regression analyses revealed depression severity negatively predicted GP performance (R2 =.099-.13), however, in patients without burn injuries, depression did not predict GP performance (R2 =.052).

Overall, results showed that GP performance is a significant predictor of neurocognitive performance on both motor and non-motor measures in EI patients with burn injuries. Therefore, among EI patients with burn injuries, GP performance may have potential utility as an early indicator of injury severity, considering that it predicts neuropsychological test performance on measures of psychomotor speed and executive functioning. Lastly, depression predicted GP performance within the burn injury sample illustrating that psychological distress may negatively impact motor functionality.

Few to no studies have directly compared the relative classification accuracies of the memory-based (Brief Visuospatial Memory Test-Revised Recognition Discrimination [BVMT-R RD] and Rey Auditory Verbal Learning Test Forced Choice [RAVLT FC]) and non-memory based (Reliable Digit Span [RDS] and Stroop Color and Word Test Word Reading trial [SCWT WR]) embedded performance validity tests (PVTs). This study’s main objective was to evaluate their relative classification accuracies head-to-head, as well as examine how their psychometric properties may vary among subgroups with and without genuine memory impairment.

This cross-sectional study included 293 adult patients who were administered the BVMT-R, WAIS-IV Digit Span, RAVLT and SCWT during outpatient neuropsychological evaluation at a Midwestern academic medical center. The overall sample was 58.0% female, 36.2% non-Hispanic White, 41.3% non-Hispanic Black, 15.7% Hispanic, 4.8% Asian/Pacific Islander, and 2.0% other, with a mean age of 45.7 (SD=15.8) and a mean education of 13.9 years (SD=2.8). Three patients had missing data, resulting in a final sample size of 290. Two hundred thirty-three patients (80%) were classified as having valid neurocognitive performance and 57 (20%) as having invalid neurocognitive performance based on performance across four independent, criterion PVTs (i.e., Test of Malingering Memory Trial 1, Word Choice Test, Dot Counting Test, Medical Symptom Validity Test). Of those with valid neurocognitive performance, 76 (48%) patients were considered as having genuine memory impairment through a memory composite band score (T<37 for (RAVLT Delayed Recall T-score + BVMT-R Delay Recall T-score/2).

The average memory composite band score for valid neurocognitive scores was T = 49.63 as compared to T = 27.57 for genuine memory impairment individuals. Receiver operating characteristic [ROC] curve analyses yielded significant areas under the curve (AUCs=.79-.87) for all four validity indices (p’s < .001). When maintaining acceptable specificity (91%-95%), all validity indices demonstrated acceptable yet varied sensitivities (35%-65%). Among the subgroup with genuine memory impairment, ROC curve analyses yielded significantly lower AUCs (.64-.69) for three validity indices (p’s < .001), except RDS (AUC=.644). At acceptable specificity (88%-93%), they yielded significantly lower sensitivities across indices (19%-39%). In the current sample, RAVLT FC and BVMT-R RD had the largest changes in sensitivities, with 19% and 26% sensitivity/90%-92% specificity at optimal cut-scores of <10 and <2, respectively, for individuals with memory impairment, compared to 65% and 61% sensitivity/94% specificity at optimal cut-scores of <13 and <4, respectively, for those without memory impairment.

Of the four validity scales, memory-based embedded PVTs yielded higher sensitivities while maintaining acceptable specificity compared to non-memory based embedded PVTs. However, they were also susceptible to the greatest declines in sensitivity among the subgroup with genuine memory impairment. As a result, careful consideration should be given to using memory-based embedded PVTs among individuals with clinically significant memory impairment based on other sources of information (e.g., clinical history, behavioral observation).