Discriminating bipolar depression from major depressive disorder with polygenic risk scores.

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.

Sodium-Glucose Cotransporter-2 Inhibitors in Depression.

ABSTRACT: 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.

Development of An All-Payer Quality Program for the Pennsylvania Rural Health Model.

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.

Acute Necrotizing Pancreatitis following Long-Term Antipsychotic Use.

Introduction. Psychiatrists commonly use antipsychotic medications in the treatment of psychotic and mood disorders. A rare but known side effect of atypical antipsychotics is acute pancreatitis. Most cases of antipsychotic-induced pancreatitis occur within six months of initiation. The mechanism believed to cause this reaction is hypertriglyceridemia. Here, we present a unique case of antipsychotic-induced pancreatitis that deviates from previous cases in the time to onset of the pancreatitis and the mechanism of presentation. Case Presentation. We present a case of a patient with treatment-resistant schizophrenia managed for over a decade on olanzapine and haloperidol. Twelve years after stabilization on this medication regimen, the patient developed acute pancreatitis, which after extensive medical workup was attributed to his psychotropic medications. We review his medical and psychiatric history, his medical course and workup during the episode of pancreatitis, and review recommendations for patients at risk for antipsychotic-induced pancreatitis based on this case and the current literature. Discussion. This case illustrates that acute pancreatitis can occur long after the initiation of antipsychotic medications and may be mediated by mechanisms other than hypertriglyceridemia. While there are reports of antipsychotic-induced psychosis occurring within months, and in a limited set of cases, years, after medication initiation, the twelve-year time interval in the present case is by far the longest duration of an antipsychotic precipitating this adverse event recorded in the literature. This case highlights that although exceedingly rare, prescribers should be aware of the risk for drug-induced pancreatitis in patients stable on antipsychotic medications.

Polygenic Risk of Schizophrenia and Cognition in a Population-Based Survey of Older Adults.

Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatric disorders with cross-sectional cognitive performance and longitudinal cognitive decline in 8616 older adults from the Health and Retirement Study (HRS), followed for an average of 10 years. PRS were computed for SCZ, bipolar disorder (BD), Major Depressive Disorder (MDD), and Alzheimer's disease (ALZ). SCZ PRS associated with decreased cognitive function (z = -3.00, P = .001, ΔR (2) = 0.04%), which was largely driven by an association with impaired attention and orientation (z = -3.33, P = 4.3×10(-4), ΔR (2) = 0.08%). We found no effect of BD or MDD PRS on cognition, in contrast to a robust effect of the APOE4/TOMM40 locus (z = -5.05, P = 2.2×10(-7), ΔR (2) = 0.36%), which was primarily associated with impaired verbal memory (z = -5.15, P = 1.3×10(-7), ΔR (2) = 0.21%). APOE4/TOMM40 locus and the ALZ PRS, but not the PRS for SCZ, were associated with greater cognitive decline. In summary, using a large, representative sample of older adults, we found evidence for different degrees of association between polygenic risk for SCZ and genetic risk factors for ALZ on cognitive function and decline, highlighting potential differences in the pathophysiology of cognitive deficits seen in SCZ and ALZ.