First episode psychoses in people over-35 years old: uncovering potential actionable targets for early intervention services.

The traditional youth-oriented design of Early Intervention Services (EIS) may lead to the exclusion of patients who have their psychotic onset later in life. A retrospective study was conducted to compare first-episode psychosis (FEP) patients who accessed treatment when aged ≤ 35 years with those ≥36+. A total of 854 patients were identified among 46,222 individuals who had access to community psychiatric services from 1991 to 2021. FEP were aged 18-65, received care between 2012 and 2021 and had a diagnosis of affective or non-affective FEP. Two groups were identified (FEP diagnosed at age ≤ 35 vs ≥ 36) and compared for sociodemographic and clinical characteristics. Most patients were diagnosed when aged ≥ 36+ (61.8%). Compared to the ≤ 35 group, older patients were more likely to be women, married and diagnosed with affective psychosis, and they were less frequently hospitalized. Long-acting injectables antipsychotics (LAI) were less frequently prescribed in the ≥ 36+ group, whereas antidepressants were more frequently prescribed compared to those aged ≤ 35. In both age groups, women were less frequently prescribed LAIs compared to men. These findings highlight the need to reorient EIS to accommodate the needs of older FEP, especially women.

Dimensions and predictors of clinical and personal recovery in first-episode psychoses: Results from a cross-sectional study.

INTRODUCTION: First episode psychosis (FEP) services ensure higher recovery rates compared to usual care. The aim of this study was to investigate the different dimensions of recovery and its predictors. METHODS: This cross-sectional study recruited within those admitted to the Ferrara FEP service since 2012 that at the time of analysis were still receiving psychiatric care. At admission, demographic, social and clinical information were collected. In September 2022, patients were assessed with the Health of the Nation Outcome Scale to evaluate clinical/functional recovery, the Recovery Assessment Scale to evaluate personal recovery, and the G12 item of the Positive and Negative Syndrome Scale to evaluate insight. Patients in recovery were compared to those not in recovery by bivariate analyses. Adjusted logistic regressions were performed to investigate predictors of recovery. RESULTS: Within 141 admitted, and 105 still receiving care, 54 patients completed the assessment. Most (51.9%) were in clinical/functional, 61.1% in personal recovery, and 38.8% both. Psychiatric hospitalization positively predicted clinical/functional recovery, whereas being prescribed oral antipsychotics was a negative predictor. Personal recovery was predicted by male sex and showed a negative association with overall severity of symptomatology. Those in personal recovery were more likely to have been prescribed long-acting antipsychotics, but this was not significant in the multivariable analysis. Poor insight negatively predicted clinical/functional recovery but had no impact on personal recovery. CONCLUSION: Our findings confirm that clinical/functional and personal recovery are semi-independent dimensions and not always overlap. Further research is needed to promote interventions targeted at all recovery dimensions.

Sex differences in schizophrenia-spectrum diagnoses: results from a 30-year health record registry.

This study investigated sociodemographic and clinical differences between the sexes in individuals affected by schizophrenia-spectrum disorders (SSD) who accessed outpatient mental health services. Within a retrospective cohort of 45,361 outpatients receiving care in Ferrara (Italy) from 1991 to 2021, those with a SSD diagnosis were compared between the sexes for sociodemographic and clinical characteristics before and after the index date (when the ICD-9: 295.*diagnosis was first recorded) to assess early trajectory, age and type of diagnosis, and severity of illness indicated by medication use, hospitalization, and duration of psychiatric care. Predictors of discharge were also investigated. Among 2439 patients, 1191 were women (48.8%). Compared to men, women were significantly older at first visit (43.7 vs. 36.8 years) and at index date (47.8 vs. 40.6) with peak frequency at age 48 (vs. 30). The most frequent last diagnosis recorded before the index date was delusional disorder (27.7%) or personality disorder (24.3%) in men and depression (24%) and delusional disorder (30.1%) in women. After the index date, long-acting antipsychotics and clozapine were more frequently prescribed to men (46.5% vs. 36.3%; 13.2% vs. 9.4%, p < 0.05) and mood stabilizers and antidepressants to women (24.3% vs. 21.1%; 50.1% vs. 35.5%; p < 0.05). Women had fewer involuntary admissions (10.1% vs. 13.6%) and were more likely to be discharged as the time under care increased (p = 0.009). After adjusting for covariates, sex was not a significant predictor of discharge. Our study confirmed that sex differences exist in clinical and sociodemographic characteristics of outpatients with SSD and that gender considerations might influence the rapidity of diagnosis and medications prescribed. These findings highlight the need to implement a women-tailored approach in specialist care programs for psychoses.

Establishment of a Public Mental Health Database for Research Purposes in the Ferrara Province: Development and Preliminary Evaluation Study.

Background: The immediate use of data exported from electronic health records (EHRs) for research is often limited by the necessity to transform data elements into an actual data set. Objective: This paper describes the methodology for establishing a data set that originated from an EHR registry that included clinical, health service, and sociodemographic information. Methods: The Extract, Transform, Load process was applied to raw data collected at the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, from 1925 to February 18, 2021, to build the new, anonymized Ferrara-Psychiatry (FEPSY) database. Information collected before the first EHR was implemented (ie, in 1991) was excluded. An unsupervised cluster analysis was performed to identify patient subgroups to support the proof of concept. Results: The FEPSY database included 3,861,432 records on 46,222 patients. Since 1991, each year, a median of 1404 (IQR 1117.5-1757.7) patients had newly accessed care, and a median of 7300 (IQR 6109.5-9397.5) patients were actively receiving care. Among 38,022 patients with a mental disorder, 2 clusters were identified; the first predominantly included male patients who were aged 25 to 34 years at first presentation and were living with their parents, and the second predominantly included female patients who were aged 35 to 44 years and were living with their own families. Conclusions: The process for building the FEPSY database proved to be robust and replicable with similar health care data, even when they were not originally conceived for research purposes. The FEPSY database will enable future in-depth analyses regarding the epidemiology and social determinants of mental disorders, access to mental health care, and resource utilization.

A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy.

Dramatic improvements in cancer survival have occurred in the last decade, but the quality of life for many survivors is compromised due to severe, long-lasting, and often irreversible side effects of chemotherapy. The neurological side effects, chemotherapy induced peripheral neuropathy (CIPN) and cancer related/induced cognitive impairment (CRCI/CICI), are under-recognized and can occur after chemotherapy, immunotherapy, or radiation. The cellular mechanisms underlying these neurological side effects are poorly understood and there are no effective treatments or preventions, other than reduction or termination of cancer therapy. In our preliminary prospective, non-interventional study to examine the side effects of chemotherapy in patients with breast cancer (NCT03872141), patients with breast cancer who received standard of care single agent weekly taxane-based chemotherapy were assessed at baseline, midpoint, and end of treatment for neurological and cognitive changes and for blood levels of potential protein biomarkers (n = 13). CIPN and CRCI both showed an increase in severity with accumulating taxane and these changes were compared to protein alternations over the course of treatment. Using peripheral blood collected from patients (n = 10) during chemotherapy and tested with an antibody array curated by the MD Anderson RPPA Core), we found that 19 proteins were increased, and 12 proteins decreased over 12 weeks of treatment. Among those downregulate were proteins known to be critical for neuronal viability and function including GRB2 (growth factor receptor-bound protein 2) and NCS1 (neuronal calcium sensor 1). Concurrently, proteins associated with apoptosis, including BAK1 (Bcl-1 homologous antagonist/killer), were upregulated. These results support the proposal that CIPN and CRCI increase with increasing taxane exposure, and identified several proteins that are altered with taxane exposure that could be implicated in their pathogenesis. In conclusion, our study provides evidence for progressive neurological changes and the rationale to investigate the molecular basis for these changes with the goal of target identification for mitigation of these neurological side effects.

The Impact of Mutations in Wolframin on Psychiatric Disorders.

Wolfram Syndrome is a rare autosomal recessive disease characterized by early-onset diabetes mellitus, neurodegeneration, and psychological disorders. Mutations in the gene WFS1, coding for the protein wolframin, cause Wolfram Syndrome and are associated with bipolar disorder and schizophrenia. This report aims to connect WFS1 mutations to their impact on protein expression and structure, which ultimately translates to altered cell function and behavioral alterations of an individual. Methods: Published data were used to compile WFS1 mutations associated with psychiatric symptoms, both in homozygous patients and heterozygous carriers of WFS1 mutations. These mutations were evaluated in silico using SNAP2, PolyPhen-2, and PROVEAN to predict the effects of sequence variants. Statistical analysis was performed to assess the correlation between the locations of the mutations and the damage prediction scores. Results: Several mutations, clustering in the center and C-terminus of the WFS1 polypeptide, such as A559T and R558C, are found in individuals with psychiatric diseases and appear particularly impactful on protein structure. Our analysis showed that mutations in all regions of wolframin were present in patients with schizophrenia whereas only cytoplasmic and ER luminal mutations were reported in patients with manic episodes and bipolar disorders. According to Poly-Phen-2 predictions, 82.4% of the ER lumen mutations and 85.7% of the membrane mutations are damaging. Conclusion: We propose mood disorders in Wolfram Syndrome and heterozygous carriers of WFS1 mutations are the consequence of specific mutations in WFS1 that alter the structure of wolframin, resulting in intracellular calcium dysregulations and impaired cell signaling, Understanding the effect of WFS1 mutations on bipolar disorder and schizoprenia is integral to designing clinically targeted treatments for both diseases, which need more specialized treatments.

Cognitive Effects and Depression Associated With Taxane-Based Chemotherapy in Breast Cancer Survivors: A Meta-Analysis.

Purpose: This meta-analysis provides a longitudinal assessment of depression and cognitive impairment induced by taxane-based chemotherapy in women with breast cancer after 6 months of treatment. We highlighted the incidence and prevalence, the cognitive pattern in neuropsychological studies, and the relationship between chemotherapy-induced cognitive impairment and different risk factors. We estimated the effect sizes on each cognitive domain and differentiated effect sizes by each method of comparison of effects (i.e., baseline data, or control groups). Methods: The databases MEDLINE and Embase were searched for publications about taxane-related cognitive changes in patients with breast cancer published from 1980 to 2019. Cross-sectional and self-reported outcomes studies were excluded except for the depression item. Included studies were assessed for risk of bias with the Newcastle-Ottawa Scale. We estimated effect sizes for each cognitive domain and differentiated effect sizes by each method of comparison of effects. The review is reported in compliance with the PRISMA Statement; it was registered prospectively in PROSPERO as CRD42020163255. Results: Eleven studies meeting the criteria were analyzed, which resulted in a sample of 1,057 patients with breast cancer who received chemotherapy including 820 patients (77%) who received taxane-based chemotherapy. Attention and concentration, depression, and executive function domains had significant chemotherapy-induced impairment across all comparison types. Statistically significant improvement was found in language and verbal memory when comparing chemotherapy patients' test scores with baseline or matched controls. Taxane-based chemotherapy had a non-significant effect on processing speed, visual memory, visuospatial, and motor function domains. Conclusions: The occurrence of chemotherapy-induced cognitive impairment 6 months or more after the course of treatment in people with breast cancer is frequent in the domains of attention, executive function, and depression. Other domains appear stable or improve with time after treatment cessation.