Faculty Bibliography

The decisional reference point, the central mechanism underlying behavioral economics, conditions our evaluations of all reinforcers. Whether a given event is experienced as positive or negative depends on this reference point. A pathological elevation of the reference point would lead a person to experience once pleasurable activities as negative reinforcers. Thus, it has been hypothesized that a reference point pathology may play a critical role in the symptomology of major depressive disorder (MDD). Here, we test the hypothesis that the reference point is pathologically elevated and dynamically inflexible in patients suffering with MDD compared to healthy controls. We find that depression is associated with a significant elevation of the reference point, and the magnitude of this elevation correlates with disease severity. The ability of patients with MDD to dynamically adjust their reference point to the environment is also dysfunctional. Our findings link the previously demonstrated treatment of depression by deep brain stimulation to modulation of the reference point in the anterior cingulate cortex and identify pathology in the dynamics of reference point setting as a potential cognitive mechanism in the disorder. Finally, these results reveal that a three-minute video game-like task measuring the reference point strongly correlates with depression severity. After further testing for clinical validity, this rapid assay may serve as a potential tool for assessing and monitoring depression.

IMPORTANCE/UNASSIGNED:Bariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy in the treatment of obesity. However, concerns of risk of suicidality with these medicines have been raised. OBJECTIVE/UNASSIGNED:To evaluate the risk of suicidality and self-harm in randomized, placebo-controlled trials of GLP-1 RAs in adults with diabetes or obesity. DATA SOURCES/UNASSIGNED:MEDLINE, Embase, ClinicalTrials.gov, and Cochrane databases were systematically searched from inception to August 29, 2023. STUDY SELECTION/UNASSIGNED:Reports of randomized clinical trials (RCTs) lasting 6 or more months comparing GLP-1 RAs with placebo for the treatment of diabetes or obesity published in peer-reviewed journals were identified. Two independent reviewers screened all search-identified studies for inclusion. Records of outcomes were queried from primary papers, ClinicalTrials.gov entries, and corresponding authors. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Two independent researchers abstracted data and assessed data quality and validity using PRISMA guidelines. Data were pooled using random-effects models. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Pooled incidence of completed or attempted suicide, occurrences of suicidal ideation, or self-harm. RESULTS/UNASSIGNED:A total of 27 of 144 RCTs meeting inclusion criteria systematically recorded suicide and/or self-harm-related events and included 32 357 individuals receiving GLP-1 RAs and 27 046 treated with placebo, over 74 740 and 68 095 person-years of follow-up, respectively. Event incidence was very low in the GLP-1 RA (0.044 per 100 person-years) and placebo (0.040 per 100 person-years) groups, with no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; P = .24). Subgroup analyses did not suggest differences in outcomes based on diabetes status or GLP-1 RA used. Five studies were considered at risk of bias due to the loss of more than 5% of participants to follow-up. Otherwise, studies were not found to be heterogeneous nor at high risk of bias. CONCLUSIONS AND RELEVANCE/UNASSIGNED:There is unlikely to be an increase in the very low incidence of suicide-related adverse events among individuals receiving GLP-1 RAs within the context of RCTs. While these findings may further ease concerns about these adverse effects, continued monitoring is warranted to identify particular patients who may be at risk as extended use of GLP-1 RAs expands.

Novel treatment strategies that refract existing treatment algorithms for depressive disorders are being sought. Abnormal brain bioenergetic metabolism may represent an alternative, therapeutically targetable neurobiological basis for depression. A growing body of research points to endogenous ketones as candidate neuroprotective metabolites with the potential to enhance brain bioenergetics and improve mood. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally approved for the treatment of diabetes, induce ketogenesis and are associated with mood improvement in population-based studies. In this column, we highlight the rationale for the hypothesis that ketogenesis induced by SGLT2 inhibitors may be an effective treatment for depressive disorders.

In the article, the authors present a multi-agent model that simulates the development of the COVID-19 pandemic at the regional level. The developed what-if system is a multi-agent generalization of the SEIR epidemiological model, which enables predicting the pandemic's course in various regions of Poland, taking into account Poland's spatial and demographic diversity, the residents' level of mobility, and, primarily, the level of restrictions imposed and the associated compliance. The developed simulation system considers detailed topographic data and the residents' professional and private lifestyles specific to the community. A numerical agent represents each resident in the system, thus providing a highly detailed model of social interactions and the pandemic's development. The developed model, made publicly available as free software, was tested in three representative regions of Poland. As the obtained results indicate, implementing social distancing and limiting mobility is crucial for impeding a pandemic before the development of an effective vaccine. It is also essential to consider a given community's social, demographic, and topographic specificity and apply measures appropriate for a given region.

PURPOSE:Measuring rural health care quality is challenging, and payer and government reporting requirements are frequently misaligned. The Pennsylvania Rural Health Model, a multipayer global budget demonstration for rural hospitals, initially required the proposal of an All-Payer Quality (APQ) Program in which participating payers would have held participating hospitals accountable for performance on a common set of quality measures. We sought to identify quality measures appropriate for use in APQ measurement and reporting programs for globally budgeted rural hospitals. METHODS:A method was devised to identify, assess, and select quality measures from an environmental scan of core measure sets. An initial screen identified measures that were relevant, valid, and reliable. Four reviewers then independently assessed measures that passed the initial screen on a Likert scale of 1-5 for relevance, validity, reliability, responsiveness, alignment, and feasibility, and they selected a proposed measure set guided by prespecified measure set criteria. RESULTS:The 4 reviewers selected 10 quality measures from a list of 344 measures drawn from 8 core measure sets. One hundred twenty-five measures satisfied screening criteria and were assessed. The mean total score was 21.5/30 (95% CI: 17.0-26.0). Inter-rater reliability was moderate (intraclass correlation coefficient range 0.544-0.656). CONCLUSION:A formal performance measure selection methodology can generate a set of rural-appropriate health care quality measures for a multipayer rural hospital global budget program. This methodology could be replicated to select quality measures for inclusion in rural multipayer quality measurement and reporting programs.

BACKGROUND:Although accurate differentiation between bipolar disorder (BD) and unipolar major depressive disorder (MDD) has important prognostic and therapeutic implications, the distinction is often challenging based on clinical grounds alone. In this study, we tested whether psychiatric polygenic risk scores (PRSs) improve clinically based classification models of BD v. MDD diagnosis. METHODS:Our sample included 843 BD and 930 MDD subjects similarly genotyped and phenotyped using the same standardized interview. We performed multivariate modeling and receiver operating characteristic analysis, testing the incremental effect of PRSs on a baseline model with clinical symptoms and features known to associate with BD compared with MDD status. RESULTS:We found a strong association between a BD diagnosis and PRSs drawn from BD (R2 = 3.5%, p = 4.94 × 10-12) and schizophrenia (R2 = 3.2%, p = 5.71 × 10-11) genome-wide association meta-analyses. Individuals with top decile BD PRS had a significantly increased risk for BD v. MDD compared with those in the lowest decile (odds ratio 3.39, confidence interval 2.19-5.25). PRSs discriminated BD v. MDD to a degree comparable with many individual symptoms and clinical features previously shown to associate with BD. When compared with the full composite model with all symptoms and clinical features PRSs provided modestly improved discriminatory ability (ΔC = 0.011, p = 6.48 × 10-4). CONCLUSIONS:Our study demonstrates that psychiatric PRSs provide modest independent discrimination between BD and MDD cases, suggesting that PRSs could ultimately have utility in subjects at the extremes of the distribution and/or subjects for whom clinical symptoms are poorly measured or yet to manifest.