Nunez, Nicolas

AbstractTo date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD‐PRS in a LAT population. Using results from the largest genome‐wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD‐PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity‐related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities.

Abstract Purpose Recognizing the negative impact that antipsychotic-induced movement disorders have on the quality of life and treatment outcomes in bipolar disorder (BD), this study aimed to assess clinical correlates and antipsychotic use patterns of tardive dyskinesia (TD+) in BD. Materials and Methods Participants with and without TD were included. Clinical variables were compared using t-test and χ2 test. Antipsychotic use patterns in TD+, including number of trials, mean doses, and estimated cumulative exposure, were assessed in a case-only analysis. Results The prevalence rate of TD was 5.1%. In comparison to the TD− group (n = 1074), TD+ participants (n = 58) were older, more likely to be female and have type I bipolar illness. There were 60.3% of the TD+ group that continued using antipsychotics at study entry and had a mean cumulative exposure to antipsychotics of 18.2 ± 15.6 years. Average dose, in haloperidol equivalents, was 5.9 ± 3.5 mg and 77.7% of the trials were second-generation antipsychotics. Conclusions This study confirms previously identified TD risk factors, such as age, sex, and bipolar subtype in a large BD cohort. Limitations included a cross-sectional design and the lack of tardive illness severity assessment. As atypical antipsychotics continue to be primary mood stabilization treatment, attempting to harmonize large data sets to identify additional biomarkers of tardive risk will optimize individualized care for patients with BD.

AbstractBackgroundWomen are nearly twice as likely as men to suffer from major depressive disorder. Yet, there is a dearth of studies comparing the clinical outcomes of women and men with treatment-resistant depression (TRD) treated with similar augmentation strategies. We aimed to evaluate the effects of the augmentation strategies in women and men at the McGill University Health Center.MethodsWe reviewed health records of 76 patients (42 women, 34 men) with TRD, treated with augmentation strategies including antidepressants (AD) with mood stabilizers (AD+MS), antipsychotics (AD+AP), or in combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Åsberg Depression Rating Scale (MADRS), Quick Inventory of Depressive Symptomatology (QIDS-C16), and Clinical Global Impression rating scale (CGI-S) at the beginning and after 3 months of an unchanged treatment. Changes in individual items of the HAMD-17 were also compared between the groups.ResultsWomen and men improved from beginning to 3 months on all scales (P < .001, η p2 ≥ 0.68). There was also a significant sex × time interaction for all scales (P < .05, η p2 ≥ 0.06), reflecting a greater improvement in women compared with men. Specifically, women exhibited greater improvement in early (P = .03, η p2 = 0.08) and middle-of-the-night insomnia (P = .01, η p2 = 0.09) as well as psychomotor retardation (P < .001 η p2 = 0.16) and psychic (P = .02, η p2 = 0.07) and somatic anxiety (P = .01, η p2 = 0.10).ConclusionsThe combination of AD+AP/MS generates a significantly greater clinical response in women compared with men with TRD, supporting the existence of distinct pharmacological profiles between sexes in our sample. Moreover, they emphasize the benefit of augmentation strategies in women, underscoring the benefit of addressing symptoms such as insomnia and anxiety with AP and MS.

Background: Psychotic symptoms are common in Alzheimer’s disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective: To establish research criteria for the diagnosis of psychosis in AD. Methods: The International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.