Exploring peripheral biomarkers of response to simvastatin supplementation in schizophrenia.

Schizophrenia is one of the most debilitating mental disorders, and its diagnosis and treatment present significant challenges. Several clinical trials have previously evaluated the effectiveness of simvastatin, a lipid-lowering medication, as a novel add-on treatment for schizophrenia. However, treatment effects varied highly between patients and over time. In the present study, we aimed to identify biomarkers of response to simvastatin in recent-onset schizophrenia patients. To this end, we profiled relevant immune and metabolic markers in patient blood samples collected in a previous clinical trial (ClinicalTrials.gov: NCT01999309) before simvastatin add-on treatment was initiated. Analysed sample types included serum, plasma, resting-state peripheral blood mononuclear cells (PBMCs), as well as PBMC samples treated ex vivo with immune stimulants and simvastatin. Associations between the blood readouts and clinical endpoints were evaluated using multivariable linear regression. This revealed that changes in insulin receptor (IR) levels induced in B-cells by ex vivo simvastatin treatment inversely correlated with in vivo effects on cognition at the primary endpoint of 12 months, as measured using the Brief Assessment of Cognition in Schizophrenia scale total score (standardised ß ± SE = -0.75 ± 0.16, P = 2.2 × 10-4, Q = 0.029; n = 21 patients). This correlation was not observed in the placebo group (ß ± SE = 0.62 ± 0.39, P = 0.17, Q = 0.49; n = 14 patients). The candidate biomarker explained 53.4 % of the variation in cognitive outcomes after simvastatin supplementation. Despite the small sample size, these findings suggest a possible interaction between the insulin signalling pathway and cognitive effects during simvastatin therapy. They also point to opportunities for personalized schizophrenia treatment through patient stratification.

Proof-of-Concept Support for the Development and Implementation of a Digital Assessment for Perinatal Mental Health: Mixed Methods Study.

BACKGROUND: Perinatal mental health symptoms commonly remain underdiagnosed and undertreated in maternity care settings in the United Kingdom, with outbreaks of disease, like the COVID-19 pandemic, further disrupting access to adequate mental health support. Digital technologies may offer an innovative way to support the mental health needs of women and their families throughout the perinatal period, as well as assist midwives in the recognition of perinatal mental health concerns. However, little is known about the acceptability and perceived benefits and barriers to using such technologies. OBJECTIVE: The aim of this study was to conduct a mixed methods evaluation of the current state of perinatal mental health care provision in the United Kingdom, as well as users' (women and partners) and midwives' interest in using a digital mental health assessment throughout the perinatal period. METHODS: Women, partners, and midwives were recruited to participate in the study, which entailed completing an online survey. Quantitative data were explored using descriptive statistics. Open-ended response data were first investigated using thematic analysis. Resultant themes were then mapped onto the components of the Capability, Opportunity, and Motivation Behavior model and summarized using descriptive statistics. RESULTS: A total of 829 women, 103 partners, and 90 midwives participated in the study. The provision of adequate perinatal mental health care support was limited, with experiences varying significantly across respondents. There was a strong interest in using a digital mental health assessment to screen, diagnose, and triage perinatal mental health concerns, particularly among women and midwives. The majority of respondents (n=781, 76.42%) expressed that they would feel comfortable or very comfortable using or recommending a digital mental health assessment. The majority of women and partners showed a preference for in-person consultations (n=417, 44.74%), followed by a blended care approach (ie, both in-person and online consultations) (n=362, 38.84%), with fewer participants preferring online-only consultations (n=120, 12.88%). Identified benefits and barriers mainly related to physical opportunity (eg, accessibility), psychological capability (eg, cognitive skills), and automatic motivation (eg, emotions). CONCLUSIONS: This study provides proof-of-concept support for the development and implementation of a digital mental health assessment to inform clinical decision making in the assessment of perinatal mental health concerns in the United Kingdom.