Faculty Bibliography

INTRODUCTION/BACKGROUND:High tobacco smoking prevalence in people with low SES or serious psychological distress (SPD) in the U.S. may increase cardiovascular disease (CVD) risk among these marginalized subpopulations. We estimate how smoking disparities contribute to CVD disparities. METHODS:Using the Simulation of Tobacco and Nicotine Outcomes and Policy model, a validated microsimulation model of tobacco use and clinical outcomes, we used 2004-2019 data from the National Health Interview Survey to first compare 20-year cumulative CVD incidence for 40-year-olds by sex, smoking status, and marginalized subpopulation membership. Second, we simulated the marginalized subpopulations with representative age, sex, and smoking status distributions to estimate 20-year cumulative CVD incidence under status quo and counterfactual scenarios. In the counterfactual scenario, smoking prevalence and trends in the low SES and SPD subpopulations match those in the higher SES and non-SPD subpopulations, respectively. RESULTS:The model-projected impact of smoking on 20-year cumulative CVD incidence is considerably larger than the impact of low SES or SPD; for example, among 40-year-old males, cumulative CVD incidence is 28.3% for low SES people who currently smoke, 13.0% for low SES people who never smoke, and 26.2% for higher SES people who currently smoke. In the second analysis, in the status quo scenario, model-projected 20-year cumulative CVD incidence is 19.3% for low SES and 22.1% for SPD; in the counterfactual scenario, it is 18.1% for low SES and 19.6% for SPD. CONCLUSIONS:Interventions focused on reducing smoking disparities could substantially reduce CVD in marginalized subpopulations.

Individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit varied responses to pharmacological treatments (e.g. stimulants and non-stimulants). Accurately and promptly detecting treatment-related improvements, response failure, or deterioration poses significant challenges, as current monitoring primarily relies on subjective ratings. In this commentary, we critically evaluate the evidence supporting the use of QbTest for objectively monitoring ADHD treatment response in clinical practice. We also offer recommendations for future research, advocating for rigorous clinical trials and longitudinal studies to further explore the potential utilisation of QbTest and other tools for monitoring treatment responses in individuals with ADHD.

INTRODUCTION/BACKGROUND: High-functioning depression (HFD) is described as experiencing depressive symptoms such as fatigue, anhedonia, poor concentration, guilt, restlessness, sleep disturbances, and appetite changes without experiencing a lack of functioning or significant distress. The purpose of this study is to characterize the clinical correlates of HFD. METHODS:This study entailed a descriptive, cross-sectional design based on interviews administered to120 English-speaking participants with HFD (aged 18-75). The interview involved administering a semi-structured HFD Analysis Questionnaire, the Joseph HFD Inventory, the HFD Trauma Inventory, and the Joseph HFD Anhedonia Scale in a single, 30-minute session for each participant. Big traumas, defined as extremely traumatic events, were analyzed by the trauma inventory. RESULTS:Out of the 120 participants, 72 (60%) demonstrated HFD, and 17 (14%) demonstrated very HFD. A correlation was observed between symptoms of HFD, such as anhedonia and marital status, as post hoc tests showed that the average Anhedonia Scale score was higher for married or partnered participants than those who were single (p=0.038). As anticipated, the participants with higher Anhedonia Scale scores had higher HFD scores (p=0.003). These participants also experienced higher trauma inventory scores and big traumas. Furthermore, as participant education level increased, the number of big traumas reported decreased (p<0.001). Participants who were parents/caregivers of children also had the highest Anhedonia Scale and HFD scores (p=0.0126 and p=0.0210, respectively). CONCLUSION/CONCLUSIONS:The results supported the hypothesis that individuals with HFD have increased levels of anhedonia and trauma. However, trauma scores were inversely associated with education level in HFD.

BACKGROUND:Randomised controlled trials (RCTs) evaluating ADHD medications often use strict eligibility criteria, potentially limiting generalisability to patients in real-world clinical settings. We aimed to identify the proportion of individuals with ADHD who would be ineligible for medication RCTs and evaluate differences in treatment patterns and clinical and functional outcomes between RCT-eligible and RCT-ineligible individuals. METHODS:We used multiple Swedish national registries to identify individuals with ADHD, aged at least 4 years at the age of diagnosis, initiating pharmacological treatment between Jan 1, 2007, and Dec 31, 2019, with follow-up up to Dec 31, 2020. Hypothetical RCT ineligibility was established using exclusion criteria from the international MED-ADHD dataset, including 164 RCTs of ADHD medications. Cox models evaluated differences in medication switching and discontinuation within 1 year between eligible and ineligible individuals. Quasi-Poisson models compared eligible and ineligible individuals on rates of psychiatric hospitalisations, injuries or accidents, and substance use disorder within 1 year of initiating ADHD medications. People with lived experience of ADHD were not involved in the research and writing process. FINDINGS/RESULTS:Of 189 699 individuals included in the study cohort (112 153 men and boys [59%] and 77 546 women and girls [41%]; mean age 21·52 years [SD 12·83; range 4-68]) initiating ADHD medication, 53% (76 477 [74%] of 103 023 adults [aged >17 years], 12 658 [35%] of 35 681 adolescents [aged 13-17 years], and 10 643 [21%] of 50 995 children [aged <13 years]) would have been ineligible for RCT participation. Ethnicity data were not available. Ineligible individuals had a higher likelihood of treatment switching (hazard ratio 1·14, 95% CI 1·12-1·16) and a decreased likelihood of medication discontinuation (0·96, 0·94-0·98) compared with eligible individuals. Individuals ineligible for RCTs had significantly higher rates of psychiatric hospitalisations (ncidence rate ratio 9·68, 95% CI 9·57-9·78) and specialist care visits related to substance use disorder (14·78, 14·64-14·91), depression (6·00, 5·94-6·06), and anxiety (11·63, 11·56-11·69). INTERPRETATION/CONCLUSIONS:Individuals ineligible for ADHD medication trials face higher risks of adverse outcomes. This study provides the first empirical evidence for the limited generalisability of ADHD RCTs to real-world clinical populations, by applying eligibility criteria extracted from a comprehensive dataset of RCTs to a large real-world cohort. Triangulating evidence from RCTs and real-world studies is crucial to inform rigorous evidence-based treatment guidelines. FUNDING/BACKGROUND:National Institute of Healthcare and Research, European Union's Horizon 2020, and Swedish Research Council.

Although parenting interventions are recommended by major clinical guidelines for managing children's behavioral challenges, including ADHD, their uptake in clinical practice remains limited. Building on the contributions of Hodson et al. and Nijboer et al. in the current issue of this journal, we here explore solutions to enhance this uptake. We first summarize the usual suspects: solutions that could be implemented in our current mental healthcare systems. Digital and brief interventions could remove obstacles that are often experienced with traditional parenting interventions, and nudges inspired by behavioral economic theories can help remove dynamic, time-varying barriers experienced by parents that may arise during the course of the intervention. We then zoom out and present a paradigmatic challenge. The current narrative surrounding behavioral problems like ADHD is predominantly biomedical, which tends to elevate expectations for treatments such as medication while simultaneously diminishing confidence in parenting interventions. From this perspective, it is unsurprising that engagement issues arise when a context-focused intervention such as parent training is proposed as a solution to a decontextualized problem like ADHD. Adopting a truly balanced biopsychosocial-societal perspective on behavioral problems like ADHD would better reflect their complex and heterogeneous etiology, and would broaden the scope for interventions, such as parenting programs, that focus on optimizing children's contextual environments.

We aimed to examine the role of shared decision-making (SDM) in family participation in the treatment of adolescents and young adults with first-episode psychosis (FEP). Based on responses of 144 family members of OnTrackNY (OTNY) participants, we divided the sample into low participators and high participators. We calculated the total SDM score for each participant by summing the ratings across items inquiring about SDM and assessed the extent to which loved ones encouraged family participation in their care. Our results indicated that the level of loved ones' encouragement was significantly related to family participation. When controlling for loved ones' encouragement, we found that the total SDM score was significantly higher in the high participator group. These findings suggest that SDM may be influenced by loved ones' attitudes towards family involvement in treatment and SDM may play a role in promoting family participation in care for individuals with FEP.

The differential influence of sex on premature mortality in schizophrenia is unclear. This study assessed the differences in all-cause and specific cause mortality risks in people with schizophrenia compared to several control groups stratified by sex. We conducted a PRISMA 2020-compliant systematic review and random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) for people with schizophrenia, comparing by sex. We measured publication bias and conducted a quality assessment through the Newcastle-Ottawa scale. We meta-analyzed 43 studies reporting on 2,700,825 people with schizophrenia. Both males and females with schizophrenia had increased all-cause mortality vs. comparison groups (males, RR=2.62, 95%CI 2.35-2.92; females, RR=2.56, 95%CI 2.27-2.87), suicide (males, RR=9.02, 95%CI 5.96-13.67; females, RR=12.09, 95%CI 9.00-16.25), and natural cause mortality (males, RR=2.11, 95%CI 1.88-2.38; females, RR=2.14, 95%CI 1.93-2.38). No statistically significant differences in sex-dependent mortality risk emerged. There was an age-group-dependent increased mortality risk in females < 40 years vs. >/=40 years old (RR=4.23/2.17), and significantly higher risk of death due to neurological disorders (dementia) in males vs. females (RR=5.19/2.40). Increased mortality risks were often associated with specific modifiable risk factors. The increased mortality risk did not improve over time, calling for more studies to identify modifiable factors, and for better physical healthcare for males and females with schizophrenia.

Methionine aminopeptidase 2 (MetAP2) plays an important role in the regulation of protein synthesis and post-translational processing. Preclinical/clinical applications of MetAP2 inhibitors for the treatment of various diseases have been explored because of their antiangiogenic, anticancer, antiobesity, antidiabetic, and immunosuppressive properties. However, the effects of MetAP2 inhibitors on CNS diseases are rarely examined despite the abundant presence of MetAP2 in the brain. Previously, we synthesized a novel boron-containing MetAP2 inhibitor, BL6, and found that it suppressed angiogenesis and adipogenesis yet improved glucose uptake. Here, we studied the anti-inflammatory effects of BL6 in SIM-A9 microglia and in a mouse model of Alzheimer's disease generated by the intracerebroventricular (icv) injection of streptozotocin (STZ). We found that BL6 reduced proinflammatory molecules, such as nitric oxide, iNOS, IL-1β, and IL-6, together with phospho-Akt and phospho-NF-κB p65, which were elevated in lipopolysaccharide (LPS)-activated microglial SIM-A9 cells. However, the LPS-induced reduction in Arg-1 and CD206 was attenuated by BL6, suggesting that BL6 promotes microglial M1 to M2 polarization. BL6 also decreased glial activation along with a reduction in phospho-tau and an elevation in synaptophysin in the icv-STZ mouse model. Thus, our experiments demonstrate an anti-neuroinflammatory action of BL6, suggesting possible clinical applications of MetAP2 inhibitors for brain disorders in which neuroinflammation is involved.

OBJECTIVE/UNASSIGNED:This study assessed the utility and effectiveness of the new general health integration (GHI) framework among community behavioral health organizations designated as certified community behavioral health clinics (CCBHCs) or in the process of applying to become a CCBHC. METHODS/UNASSIGNED:Nineteen licensed community behavioral health clinics, 18 of which had CCBHC status, participated in a 12-month learning collaborative. They used the GHI framework to assess their integration stage for 15 subdomains within eight domains of evidence-based practice. The clinics worked to improve their GHI practices with the support of monthly learning collaborative webinars, individual consultation calls, and technical assistance sessions. Clinics reported on performance quality metrics aligned with national CCBHC standards. Outcome measures included GHI framework scores at baseline and 1-year follow-up, capacity to report quality metrics at baseline and at the end of the collaborative, and average performance on the quality metrics at baseline versus at the end of the collaborative. RESULTS/UNASSIGNED:Clinics showed overall improvement in integration stage over the study period. Of note, higher baseline GHI framework scores demonstrated a significant association with greater-quality performance at baseline (r=0.577, p=0.024) and follow-up (r=0.782, p=0.001). Capacity to track and report quality metrics increased significantly during the learning collaborative, as did average performance on quality metrics. CONCLUSIONS/UNASSIGNED:Community behavioral health clinics using the GHI framework were able to advance their GHI practices with a 12-month learning collaborative project. The framework has the potential to serve as a useful tool for clinics aiming to enhance GHI practices.