Second Opinions for Diagnoses of Psychotic Disorders: Delivering Stage-Specific Recommendations.

OBJECTIVE: The impact of obtaining second-opinion consultations on diagnoses of schizophrenia spectrum disorders was evaluated. METHODS: A retrospective chart review was conducted for 177 patients referred to a psychosis consultation service at an academic medical center from January 1, 2017, to October 1, 2023; these consultations aimed to clarify a diagnosis of psychosis. Diagnoses made before and after consultations were compared, and treatment recommendations resulting from the consultation visit were summarized. RESULTS: Among patients without a preconsultation diagnosis of schizophrenia, 28% (N=28 of 100) received a postconsultation diagnosis of schizophrenia. Among 62 patients with a postconsultation diagnosis of treatment-resistant schizophrenia (TRS), 56% (N=35) received this diagnosis only after consultation. Nearly all of these patients were advised to begin taking clozapine, and electroconvulsive therapy was less commonly recommended. CONCLUSIONS: Expert consultation facilitates timely identification and optimal treatment of schizophrenia and its more severe subtype, TRS.

Increasing COVID-19 Vaccination Rates Among Patients With Serious Mental Illness: A Pilot Intervention Study.

OBJECTIVE: This pilot project aimed to maximize COVID-19 vaccine uptake among patients with serious mental illness. Psychiatric providers were engaged to directly address COVID-19 vaccine-related concerns with patients during outpatient visits. METHODS: A quality improvement project encouraged COVID-19 vaccinations in a cohort of outpatients treated with clozapine (N=193, ages 19-81 years, mean age=46.4 years) at a community mental health center. In-service education was provided to clinicians to identify vaccine-hesitant patients and build vaccine confidence. A vaccination-monitoring tool was created and embedded in patients' electronic medical records. Starting in February 2021, the tool guided semistructured interviews at each visit and supported population-based management. RESULTS: The full COVID-19 vaccination rate by June 30, 2021, was 84% among the outpatients, compared with the estimated state rate on the same date of between 62.1% and 77.3%. CONCLUSIONS: The active involvement of psychiatric providers in preventive health care can help increase vaccination rates among patients with serious mental illness.

Improved Glycemic Control in Adults With Serious Mental Illness and Diabetes With a Behavioral and Educational Intervention.

OBJECTIVE: The purpose of this study was to evaluate a 16-week, reverse-integrated care (bringing primary care interventions/services into the psychiatric setting) behavioral and educational group intervention for individuals with serious mental illness and diabetes. METHODS: The primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included body mass index (BMI), blood pressure, lipid levels, physical activity, diabetes knowledge, and self-care. RESULTS: Thirty-five participants attended at least one group and were included in a modified intent-to-treat analysis. From baseline to week 16, HbA1c improved, from 7.5±1.6 to 7.1±1.4, p=0.01, and BMI improved, from 33.3±3.8 to 32.9±4.1, p<0.001, as did measures of diabetes knowledge and self-care. One-year follow-up in a subset of participants showed no evidence of rebound in HbA1c. CONCLUSIONS: This 16-week behavioral and educational group intervention resulted in improvements in glycemic control, BMI, diabetes knowledge, and self-care. The results warrant larger-scale, controlled trial testing of this intervention to improve diabetes-related health outcomes in those with serious mental illness.

Hybrid FMT-CT imaging of amyloid-beta plaques in a murine Alzheimer's disease model.

The need to study molecular and functional parameters of Alzheimer's disease progression in animal models has led to the development of disease-specific fluorescent markers. However, curved optical interfaces and a highly heterogeneous internal structure make quantitative fluorescence imaging of the murine brain a particularly challenging tomographic problem. We investigated the integration of X-ray computed tomography (CT) information into a state-of-the-art fluorescence molecular tomography (FMT) scheme and establish that the dual-modality approach is essential for high fidelity reconstructions of distributed fluorescence within the murine brain, as compared to conventional fluorescence tomography. We employ this method in vivo using a fluorescent oxazine dye to quantify amyloid-beta plaque burden in transgenic APP23 mice modeling Alzheimer's disease. Multi-modal imaging allows for accurate signal localization and correlation of in vivo findings to ex vivo studies. The results point to FMT-CT as an essential tool for in vivo study of neurodegenerative disease in animal models and potentially humans.

Technical considerations in longitudinal multispectral small animal molecular imaging.

In a previous study, we investigated physical methods to reduce whole-body, diet-related autofluorescence interference in several mouse strains through changes in animal diet. Measurements of mice with an in vivo multispectral imaging system over a 21-day period allowed for the quantification of concentration changes in multiple in vivo fluorophores. To be an effective instrument, a multispectral imaging system requires a priori spectral knowledge, the form and importance of which is not necessarily intuitive, particularly when noninvasive in vivo longitudinal imaging studies are performed. Using an optimized spectral library from a previous autofluorescence-reduction study as a model, we investigated two additional spectral definition techniques to illustrate the results of poor spectral definition in a longitudinal fluorescence imaging study. Here we systematically evaluate these results and show how poor spectral definition can lead to physiologically irrelevant results. This study concludes that the proper selection of robust spectra corresponding to each specific fluorescent molecular label of interest is of integral importance to enable effective use of multispectral imaging techniques in longitudinal fluorescence studies.

Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze.

The apolipoprotein E receptor 2 (ApoER2), expressed predominantly in forebrain regions including the hippocampus, is 1 of 2 receptors for the extracellular matrix protein reelin, which is critical for cortical development. Previous studies of ApoER2 mutant mice have indicated deficits in synaptic plasticity and learning. The current authors assessed learning and memory of ApoER2 knockout and wild-type mice on the Barnes circular maze. Mice were trained in this task for 22 days, followed by memory recall and reversal tests. ApoER2 knockout mice were initially slower to complete the task, but by Day 22 they were more accurate than wild-type mice on several indices. There were no differences in memory assessed by the recall task, but ApoER2 knockout mice performed significantly worse on the memory reversal task. ApoER2 knockout mice also displayed altered use of specific search strategies and relationship of these strategies to errors made on the maze.

Hippocampal dendritic arbor growth in vitro: regulation by Reelin-Disabled-1 signaling.

The cytoplasmic adaptor protein Disabled-1 (Dab1), which is a key component of the Reelin-signaling pathway, has been suggested to be required for neuronal dendritic development. However, only data from studies on immature cultures [< or = 6 days in vitro (DIV)] and cytoarchitectural analyses of mutant mice have been used to formulate this hypothesis. Therefore, to determine if Reelin-Dab1 signaling is specifically required for neurons to develop mature dendrites in respect to length and complexity, we analyzed dendritic development in mature cultures derived from Dab1 knockout (ko) embryos. No significant differences in dendritic length or complexity between Dab1 ko and wt cultures were found at 20 DIV. An examination of dendritic development in maturing cultures found significant differences in dendritic length between mutant and wt cultures at 4 DIV, but detected no differences in complexity. In addition, by 7 DIV, all measures were statistically the same between cultures. Therefore, although Reelin-Dab1 signaling promotes hippocampal dendrite development, Dab1 is not required for neurons to reach maturity with respect to dendritic length and complexity. Furthermore, analyses of 4 DIV cultures derived from Dab1 heterozygotes or mice that express only the natural splice form of Dab1 (p45) found that Dab1(p45/-) hemizygote, but not Dab1(p45/p45) and Dab1 heterozygote cultures had significantly shorter dendrites than those in wt cultures. Thus, a substantial attenuation of the Reelin-Dab1 signal is required before dendrite elongation is significantly decreased at 4 DIV. Moreover, experiments that incorporated a Reelin-neutralizing antibody support the hypothesis that the role(s) Reelin-signaling plays in dendritic maturation is different than the one it has in neuronal positioning.