Schizoaffective Research Articles

Antipsychotic prescribing practices and their association with rehospitalization in a forensic psychiatric sample

While there is extensive literature examining the effectiveness of antipsychotic prescribing to patients with schizophrenia spectrum or other psychotic disorders in general psychiatric services, there is a dearth of studies examining antipsychotic prescribing practices and their effectiveness in forensic psychiatric services. Forensic psychiatric patients have unique challenges often due to their high-profile offences, public scrutiny, and legal requirements. This longitudinal, retrospective study aimed to examine antipsychotic prescribing and rehospitalization rates in a forensic psychiatric sample, along with relevant socio-demographic, clinical, and forensic characteristics. All patients had a psychotic illness and were prescribed antipsychotic medication. The sample included 153 patients, of which the majority were male (85.6%), Caucasian (71.2%), middle aged (30s to 50s), had schizophrenia or schizoaffective disorder (76.5%), had a substance use disorder (62.1%), and had a most serious index offence against the person (80.4%). Atypical antipsychotics accounted for the majority of antipsychotic prescriptions (75.9%) and the sample had an antipsychotic polypharmacy rate of 39.9%. The sample was divided into four primary antipsychotic formulation types, which were oral (34.0%), injection (39.2%), clozapine (19.0%), and subtherapeutic (7.8%). Regarding rehospitalization, 52.9% of the sample was rehospitalized, with the average number of rehospitalizations being 1.2 (SD = 1.7) and proportion of the follow up period rehospitalized being 16.4% (SD = 27.7%). Patients prescribed clozapine had numerically lower rates of rehospitalization than those prescribed oral and injection formulation types, but it was not statistically significant. With a 19.0% prescription rate, clozapine may be underutilized in this sample. Further research is needed to demonstrate the potential benefits of clozapine regarding rehospitalization in forensic psychiatric patients, as has already been done in general psychiatry. Advancing treatment of the high-profile forensic population can reduce stigma toward people with mental illness and criminal justice involvement.

Oral and Long-acting Injectable Aripiprazole in Severe Mental Illness and Substance Use Disorder Comorbidity: An Updated Systematic Review.

Co-occurrence of substance use disorders is frequent in patients with mental health disorders is a condition known as "dual diagnosis". The use of substances worsens the prognosis and lowers the quality of life of psychiatric patients. It also increases the risk of hospitalization and suicide rate. To assess the effects of aripiprazole therapy on substance use and other psychiatric outcomes in dually diagnosed patients. We performed a systematic review conducted on 3 databases PUBMED, SCOPUS, and Web of Science, selecting original studies and analyzing the impact of aripiprazole therapy on dually diagnosed patients. Six hundred and fifty-five articles were founded and, after removing duplicates (n = 274) and applying the exclusion criteria, 12 articles were included in our systematic review. 12 studies were included, among which 6 were Randomized Controlled Trials. The Most frequent psychiatric diagnosis were schizoaffective disorders, schizophrenia, and bipolar disorders. Alcohol and cocaine use disorders were the most used substances. Eleven studies showed a clinical improvement after aripiprazole treatment. 8 studies evaluated craving and found a significant reduction after treatment with aripiprazole. No definitive conclusions can be drawn on substance usage and maintenance of abstinence. The present findings suggest aripiprazole may be associated with reducing substance craving and improving depression, psychosis, and schizoaffective disorders in dually diagnosed patients.

Prevalence of schizophrenia spectrum disorders in the Lazio region, Italy: use of an algorithm based on health administrative databases

BackgroundMental healthcare provision is undergoing substantial reconfiguration in many regions of the world. Such changes require a broad, evidence-based approach incorporating epidemiological data and information on local needs. The objective of this study was to estimate the prevalence of schizophrenia spectrum disorders (SSD) in the Lazio region and its geographical distribution using regional administrative healthcare databases.MethodsCases of SSD (15–64 years old) were identified using an algorithm based on data from the hospital discharge registry (ICD IX CM: 295, 297, 298 [excl. 298.0], 299) and the ticket exemption database [code 044], between 2006 and 2019. We calculated crude, age- and gender-specific prevalence estimates on December 31, 2019. We also calculated age- and gender-adjusted prevalence to compare prevalence in different regional areas.ResultsWe identified 18,371 cases. The overall prevalence was 5.03 per 1000 population (95% CI 4.96–5.10). Age-adjusted prevalence estimates were 4.18 (95% CI 4.09–4.27) per 1000 for women and 5.92 (95% CI 5.81–6.04) per 1000 for men. The prevalence was higher among older age groups, in both genders. There were differences in prevalence within the region, ranging from 4.25/1000 in the province of Viterbo to 5.42/1000 in Rome and 6.02/1000 in the province of Frosinone. When we analysed the subcategories of SSD, the three most frequent conditions were schizophrenia, schizoaffective disorder, and psychosis NOS. In general, the prevalence was higher in men for all the conditions but delusional disorders and brief psychosis.ConclusionsOur results show that the overall prevalence of SSD among adults in the Lazio region is similar to those published in previous reviews, but an uneven regional distribution was observed. While possible underestimation must be considered, administrative databases represent a valuable source of information for epidemiological surveillance and healthcare planning.

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome: A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome (DPHLS), also known as Grinker’s myelinopathy, is a rare but significant neurological condition that manifests days to weeks after a hypoxic event. Characterized by delayed onset of neurological and cognitive deficits, DPHLS presents substantial diagnostic and therapeutic challenges. AIM To consolidate current knowledge on pathophysiology, clinical features, diagnostic approaches, and management strategies for DPHLS, providing a comprehensive overview and highlighting gaps for future research. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines, we systematically searched PubMed, ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy. Inclusion criteria were original research articles, case reports, and case series involving human subjects with detailed clinical, neuroimaging, or pathological data on DPHLS. Data were extracted on study characteristics, participant demographics, clinical features, neuroimaging findings, pathological findings, treatment, and outcomes. The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist. RESULTS A total of 73 cases were reviewed. Common comorbidities included schizoaffective disorder, bipolar disorder, hypertension, and substance use disorder. The primary causes of hypoxia were benzodiazepine overdose, opioid overdose, polysubstance overdose, and carbon monoxide (CO) poisoning. Symptoms frequently include decreased level of consciousness, psychomotor agitation, cognitive decline, parkinsonism, and encephalopathy. Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter, sometimes involving the basal ganglia and the globus pallidus. Magnetic resonance spectroscopy often showed decreased N-acetylaspartate, elevated choline, choline-to-creatinine ratio, and normal or elevated lactate. Treatment is often supportive, including amantadine, an antioxidant cocktail, and steroids. Hyperbaric oxygen therapy may be beneficial in those with CO poisoning. Parkinsonism was often treated with levodopa. Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits. CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations. Early recognition and appropriate management are crucial to improving patient outcomes. Future research should focus on standardizing diagnostic criteria, using advanced imaging techniques, and exploring therapeutic interventions to improve understanding and treatment of DPHLS. Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

Pharmacokinetics and Safety of a Novel Extended-Release Microsphere Formulation of Risperidone in Patients with Schizophrenia or Schizoaffective Disorder.

Risperidone extended-release injectable suspension (R-ERIS; marketed as RYKINDO) is a novel immediate-release version of risperidone formulated as extended-release microspheres for biweekly intramuscular injection to treat schizophrenia in adults. The pharmacokinetics (PK) and safety of R-ERIS were evaluated in a multicenter, randomized, open-label, multiple-dose study in patients with stable schizophrenia or schizoaffective disorder. Eligible patients (N = 108) 18 to 65 years old were randomized (1:1) to receive IM injections of R-ERIS 25 mg or the comparator, a biweekly risperidone long-acting injectable (BW-RLAI; marketed as RISPERDAL CONSTA) 25 mg for a total of 5 injections. The primary objective was to evaluate the relative bioavailability of active moiety (risperidone plus 9-hydroxyrisperidone) at steady state. Blood samples were analyzed for risperidone and 9-hydroxyrisperidone using a validated, specific, and sensitive liquid chromatography with tandem mass spectrometry method. Plasma concentration-time data were analyzed using non-compartmental methods. Pharmacokinetic parameters were calculated based on individual patient PK profiles. Safety was assessed using standard measures. At steady state, mean plasma concentrations of the active moiety were similar for R-ERIS and BW-RLAI. R-ERIS rapidly released risperidone after the injection without apparent lag time. Plasma active moiety levels reached steady state after the second injection of R-ERIS. The elimination of the drug was completed approximately 2weeks earlier for R-ERIS as compared to that for BW-RLAI. R-ERIS was safe and well tolerated. Overall, R-ERIS exhibited a faster onset and offset than BW-RLAI and statistical analysis of exposure parameters demonstrated bioequivalence at steady state.

Physical health challenges faced by elders with severe mental illness: population-based retrospective cohort study.

Severe mental illness (SMI), which includes schizophrenia, schizoaffective disorder and bipolar disorder, has profound health impacts, even in the elderly. To evaluate relative risk of hospital admission and length of hospital stay for physical illness in elders with SMI. To construct a population-based retrospective cohort observed from April 2007 to March 2016, data from a case registry with full but de-identified electronic health records were retrieved for patients of the South London and Maudsley NHS Foundation Trust, the single secondary mental healthcare service provider in south-east London. We compared participants with SMI aged >60 years old with the general population of the same age and residing in the same areas through data linkage by age-, sex- and fiscal-year-standardised admission ratios (SARs) for primary diagnoses at hospital discharge. Furthermore, we compared the duration of hospital stay with an age-, sex- and cause-of-admission-matched random group by linear regression for major causes of admission. In total, records for 4175 older people with SMI were obtained, relating to 10 342 admission episodes, showing an overall SAR for all physical illnesses of 5.15 (95% CI: 5.05, 5.25). Among the top causes of admission, SARs ranged from 3.87 for circulatory system disorders (ICD-10 codes: I00-I99) to 6.99 for genitourinary system or urinary conditions (N00-N39). Specifically, the diagnostic group of 'symptoms, signs and findings, not elsewhere classified' (R00-R99) had an elevated SAR of 6.56 (95% CI: 6.22, 6.90). Elders with SMI also had significantly longer hospital stays than their counterparts in the general population, especially for digestive system illnesses (K00-K93), after adjusting for confounding. Poorer overall physical health and specific patterns were identified in elders with SMI.

In brief: Erzofri - another once-monthly paliperidone formulation.

The FDA has approved Erzofri (Luye), an extended-release injectable formulation of the second-generation antipsychotic drug paliperidone palmitate, for treatment of schizophrenia and schizoaffective disorder in adults. It is the second once-monthly formulation of paliperidone palmitate to be approved in the US for these indications; Invega Sustenna was the first. Longer-acting injectable formulations of paliperidone palmitate are also available.

Impulsivity in first-degree relatives at risk of psychosis and mania: a systematic review and meta-analysis.

Impulsivity is elevated in psychosis and during mania in bipolar disorder. Studies in unaffected relatives may help establish whether impulsivity is a heritable, state independent endophenotype. The aim of this systematic review and meta-analysis was to examine whether impulsivity is elevated in unaffected relatives of those with bipolar disorder, schizophrenia, and schizoaffective disorder, compared to controls. Databases were systematically searched up until March 2023 for articles reporting data on a behavioral or self-report measure of impulsivity in first-degree relatives and controls. Nineteen studies were included. Behavioral (10 studies, d = 0.35, p < 0.001) and self-reported impulsivity was significantly elevated in bipolar disorder relatives compared to controls (5 studies, d = 0.46, p < 0.001), with small effect sizes. Relatives of those with schizophrenia did not show significantly elevated impulsivity compared to controls on behavioral measures (6 studies, d = 0.42, p = 0.102). There were not enough studies to conduct a meta-analysis on self-report data in schizophrenia relatives or schizoaffective disorder relatives (self-report or behavioral). Study quality was good, however there was moderate to high heterogeneity in behavioral meta-analyses. Results suggest elevated impulsivity may be an endophenotype for bipolar disorder, present in an attenuated state before and after the illness and in at-risk individuals. This trait, amongst other behavioral and psychological indices, could be used to identify those who are at risk of developing bipolar disorder. Future research should refine measurement across studies and establish which components of impulsivity are affected in those at risk of psychotic and bipolar disorders.

Elevated serum IL-17 A and CCL20 levels as potential biomarkers in major psychotic disorders: a case-control study

BackgroundMajor psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics.MethodWe conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS).ResultsThe mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1–15.3) pg/mL and 4.2 (3–5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20.ConclusionThe current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia.

Obsessive-compulsive symptoms relating to psychosocial functioning for people with schizophrenia, schizoaffective disorder, or bipolar disorder.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

Impact of Anticholinergic Burden on Cognitive Functions in Individuals with Bipolar Disorder, Schizoaffective Disorder, and Schizophrenia

Impact of Anticholinergic Burden on Cognitive Functions in Individuals with Bipolar Disorder, Schizoaffective Disorder, and Schizophrenia

Managing COVID-19 patients with mental illness in a specialized neuropsychiatric setting: An experience from a tertiary care hospital in India.

To explore the management and outcome of COVID-19 infection in mental illness at a specialized neuropsychiatric setting. A retrospective review of the clinical profile of 100 COVID-19 patients with mental illness, admitted to the Psychiatric COVID unit (PCU) from June 2020 to June 2022, was done, with a subgroup analysis of chronic institutionalized patients (n = 36). Schizophrenia, bipolar affective disorder, and schizoaffective disorder comprised 64% of the study population. Most patients (87%) were on antipsychotics. 56% of the patients had an infection of mild severity and 38% were asymptomatic. Corticosteroids and anticoagulants were given to 33.3% and 25% of the patients, respectively. 16% of the patients encountered medical complications in the PCU, and 14% were referred to a COVID-designated hospital. Patients with diabetes mellitus and/or hypertension were more likely to be referred. The chronic institutionalized patients (n = 36) had either an asymptomatic or mild infection. Three among these patients were referred to a COVID-designated hospital. Most psychiatric patients with medical illnesses, including COVID-19, pose unique challenges including complexity of symptoms, ensuring patient safety, and the need for trained professional staff to provide specialized psychiatric interventions, which can be taken care of in psychiatric care settings.

Deconstructing Cognitive Impairment in Psychosis With a Machine Learning Approach

Cognitive functioning is associated with various factors, such as age, sex, education, and childhood adversity, and is impaired in people with psychosis. In addition to specific effects of the disorder, cognitive impairments may reflect a greater exposure to general risk factors for poor cognition. To determine the extent that impairments in cognition in psychosis reflect risk factor exposures. This cross-sectional study examined the relationship between exposures and cognitive function using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes studies 1 and 2 across 6 sites. Participants included healthy controls; patients with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychosis; and relatives of patients. Predictive modeling was performed using extreme gradient boosting regression to train a composite cognitive score prediction model with nested cross-validation. Shapley additive explanations values were used to examine the relationship between exposures and cognitive function. Exposures were chosen based on associations with cognition previously identified: age, sex, race and ethnicity, childhood adversity, education, parental education, parental socioeconomic status, parental age at birth, substance use, antipsychotic dose, and diagnosis. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia. A total of 3370 participants were included: 840 healthy controls, 709 patients with schizophrenia, 541 with schizoaffective disorder, 457 with bipolar I disorder with psychosis, and 823 relatives of patients. The mean (SD) age was 37.9 (13.3) years; 1887 were female (56%) and 1483 male (44%). The model predicted cognitive scores with high accuracy: out-of-sample Pearson correlation between predicted and observed cognitive composite score was r = 0.72 (SD = 0.03). Individuals with schizophrenia (z = -1.4), schizoaffective disorder (z = -1.2), and bipolar I disorder with psychosis (z = -0.5) all had significantly worse cognitive composite scores than controls. Factors other than diagnosis and medication accounted for much of this impairment (schizophrenia z = -0.73, schizoaffective disorder z = -0.64, bipolar I disorder with psychosis z = -0.13). Diagnosis accounted for a lesser proportion of this deficit (schizophrenia z = -0.29, schizoaffective disorder z = -0.15, bipolar I disorder with psychosis z = -0.13), and antipsychotic use accounted for a similar deficit across diagnostic groups (schizophrenia z = -0.37, schizoaffective disorder z = -0.33, bipolar I disorder with psychosis z = -0.26). This study found that transdiagnostic factors accounted for a meaningful share of the variance in cognitive functioning in psychosis. A significant proportion of the cognitive impairment in psychosis may reflect factors relevant to cognitive functioning in the general population. When considering interventions, a diagnosis-agnostic, symptom-targeted approach may therefore be appropriate.

The modern concept of schizoaffective disorder: a narrative review

BACKGROUND: Schizoaffective disorder (SAD) is one of the most complex and controversial diagnoses in clinical psychiatry. Despite the significant changes that have occurred in the conceptualization of SAD in modern classifications and the publications of recent years, many unresolved issues remain regarding the disease, from the point of view of clinical psychiatry and basic neuroscience. AIM: The purpose of this paper is to summarize published data on the concept of SAD, its clinical characteristics, cognitive profile, potential biomarkers, as well as the place of the disease in the following modern international classifications: the International Classification of Diseases (ICD) 9th, 10th and 11th revisions, and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). METHODS: We undertook a review of the scientific studies in the relevant bibliographic systems and databases (eLIBRARY, PubMed) of the past 15 years. The descriptive analysis method was used to summarize the collected information. A total of 70 publications were selected for review, including different versions of international classifications of diseases (ICD and DSM-5). RESULTS: There has been some improvement in the inter-rater reliability of SAD criteria in modern classifications, but this has not yet led to a clearer understanding among mental health specialists, while the various subtypes of SAD identified so far fail to account for the heterogeneity in the clinical presentation of the disorder. The dimensional approach to diagnosing SAD, according to which the intensity of psychotic and affective symptoms can fluctuate over time and they can influence one another, more accurately reflects the disease’s ability to embody different forms. Basic research does not support the identification of a distinct cognitive, neuroimaging, or immunological SAD endophenotype that differs qualitatively from schizophrenia and affective psychoses. CONCLUSION: The conceptualization of SAD remains incomplete, and new approaches rooted in neuroscience are needed to better understand the coexistence of affective and psychotic symptoms.

Real-world healthcare resource utilization, costs, and predictors of relapse among US patients with incident schizophrenia or schizoaffective disorder

Schizophrenia and schizoaffective disorder present burdens to patients and health systems through elevated healthcare resource utilization (HCRU) and costs. However, there is a paucity of evidence describing these burdens across payor types. To identify unmet needs, this study characterized patients with schizophrenia or schizoaffective disorder by payor type. We identified patients aged 12–94 years with newly diagnosed schizophrenia or schizoaffective disorder (index date) between 01/01/2014 and 08/31/2020 with continuous enrollment for 12 months before and after index date from the Healthcare Integrated Research Database. After stratifying by post-index relapse frequency (0, 1, or ≥2) and payor type (commercial, Medicare Advantage/Supplemental (Medigap)/Part D, or managed Medicaid), we examined patient characteristics, treatment patterns, HCRU, costs, and relapse patterns and predictors. During follow-up, 25% of commercial patients, 29% of Medicare patients, and 37% of Medicaid patients experienced relapse. Atypical antipsychotic discontinuation was most common among Medicaid patients, with 65% of these patients discontinuing during follow-up. Compared to commercial patients, Medicare and Medicaid patients had approximately half as many psychotherapy visits during follow-up (12 vs. 5 vs. 7 visits, respectively). Relative to baseline, average unadjusted all-cause costs during follow-up increased by 105% for commercial patients, 66% for Medicare patients, and 77% for Medicaid patients. Patients with schizophrenia or schizoaffective disorder had high HCRU and costs but consistently low psychotherapy utilization, and they often discontinued pharmacologic therapy and experienced relapse. These findings illustrate the high burden and unmet need for managing these conditions and opportunities to improve care for underserved patients.

Protocol for Cancloz: multicentre randomised, placebo-controlled, double-blind, parallel-group adaptive trial of cannabidiol for clozapine-resistant schizophrenia.

Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia. To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia. This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability. Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.

Association Between Antipsychotic Medication Use and Dementia Risk in Patients With Schizophrenia or Schizoaffective Disorder.

To determine the association between antipsychotic prescriptions and incident dementia in patients with schizophrenia or schizoaffective disorder. In this retrospective cohort study, Cox Proportional hazard models estimated the association between antipsychotic prescriptions and incident dementia in participants ≥50 years of age with a schizophrenia/schizoaffective disorder diagnosis over 12years. Confounding was controlled by E-balance. Cumulative dementia incidence was significantly greater among those with an antipsychotic prescription compared to those without (7.9% vs 5.5%, P < 0.0001). After controlling for confounding, antipsychotic prescriptions were associated with a 92% increased risk for dementia (HR = 1.92; 95% CI:1.13-3.27). This association was not significant among those aged ≥65 years. Antipsychotic prescription type (eg, first generation, yes or no) did not affect dementia risk but prescription number did. Antipsychotic prescriptions were associated with almost twice the incidence of dementia compared to patients without in those with schizophrenia/schizoaffective disorder.

Polyconnectomic scoring of functional connectivity patterns across eight neuropsychiatric and three neurodegenerative disorders

BackgroundNeuropsychiatric and neurodegenerative disorders involve diverse changes in brain functional connectivity. As an alternative to approaches searching for specific mosaic patterns of affected connections and networks, we used polyconnectomic scoring to quantify disorder-related whole-brain connectivity signatures into interpretable, personalized scores. MethodsThe polyconnectomic score (PCS) measures the extent to which an individual's functional connectivity (FC) mirrors the whole-brain circuitry characteristics of a trait. We computed PCS for eight neuropsychiatric conditions (attention-deficit/hyperactivity disorder, anxiety-related disorders, autism spectrum disorder, obsessive-compulsive disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) and three neurodegenerative conditions (Alzheimer's disease, frontotemporal dementia, and Parkinson’s disease) across 22 datasets with resting-state functional MRI of 10,667 individuals (5,325 patients, 5,342 controls). We further examined PCS in 26,673 individuals from the population-based UK Biobank cohort. ResultsPCS was consistently higher in out-of-sample patients across six of the eight neuropsychiatric and across all three investigated neurodegenerative disorders ([min, max]: AUC = [0.55, 0.73], pFDR = [1.8 x 10-16, 4.5 x 10-2]). Individuals with elevated PCS levels for neuropsychiatric conditions exhibited higher neuroticism (pFDR < 9.7 x 10-5), lower cognitive performance (pFDR < 5.3 x 10-5), and lower general wellbeing (pFDR < 9.7 x 10-4). ConclusionsOur findings reveal generalizable whole-brain connectivity alterations in brain disorders. PCS effectively aggregates disorder-related signatures across the entire brain into an interpretable, subject-specific metric. A toolbox is provided for PCS computation.

Real-World Effectiveness of Menopausal Hormone Therapy in Preventing Relapse in Women With Schizophrenia or Schizoaffective Disorder.

Antipsychotic effectiveness in preventing relapse declines around menopausal age in women with schizophrenia or schizoaffective disorder (SSD). It is not known whether systemic menopausal hormone therapy (MHT) can help to prevent psychosis relapse. A within-subject study design was used to study the effectiveness of MHT in preventing relapse in a Finnish nationwide cohort of women with SSD between 40 and 62 years of age who used MHT during follow-up (1994-2017). Hazard ratios adjusted for age and psychotropic drug use were calculated for psychosis relapse as main outcome and any psychiatric hospitalization as secondary outcome. The study population comprised 3,488 women using MHT. Use of MHT was associated with a 16% lower relapse risk (adjusted hazard ratio [aHR]=0.84, 95% CI=0.78-0.90) when compared to non-use. Stratified by age, MHT was associated with decreased relapse risks when used between ages 40-49 (aHR=0.86, 95% CI=0.78-0.95) and ages 50-55 (aHR=0.74, 95% CI=0.66-0.83), but not between ages 56-62 (aHR=1.11, 95% CI=0.91-1.37). Similar effectiveness was found for estrogen alone or combined with fixed or sequential progestogens (aHRs between 0.79 and 0.86), transdermal and oral formulations (aHRs 0.75-0.87), and for most specific formulations (aHRs 0.75-0.85), except tibolone (aHR=1.04, 95% CI=0.75-1.44) and formulations with dydrogesterone (aHR=1.05, 95% CI=0.85-1.30). Similar results were observed with any psychiatric hospitalization as outcome measure. The findings underscore the potential value of MHT in preventing psychosis relapse among women with SSD of menopausal age. These findings translate clinical evidence on the neuroprotective effects of estrogens to real-world settings, encompassing a group of women for whom current antipsychotic treatment options may be insufficient.

Neurobiological correlates of comorbidity in disorders across the affective disorders-psychosis spectrum

Disorders across the affective disorders-psychosis spectrum such as major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SCA), and schizophrenia (SCZ), have overlapping symptomatology and high comorbidity rates with other mental disorders. So far, however, it is largely unclear why some of the patients develop comorbidities. In particular, the specific genetic architecture of comorbidity and its relationship with brain structure remain poorly understood. Therefore, we performed systematic analyses of clinical, genetics and brain structural measures to gain further insights into the neurobiological correlates of mental disorder’s comorbidity. We investigated a sub-sample of the Marburg/Münster Cohort Study (MACS), comprising DSM-IV-TR diagnosed patients with a single disorder in the affective disorders-psychosis spectrum (SD, n=470, MDD; BD; SCA; SCZ), with additional mental disorder’s comorbidities (COM, n=310), and healthy controls (HC, n=649). We investigated group differences regarding a) the global severity index (based on SCL90-R), b) a cross-disorder polygenic risk score (PRS) calculated with PRS-continuous shrinkage (PRS-CS) using the summary statistics of a large genome-wide association study across mental disorders, and c) whole brain grey matter volume (GMV). The SCL90-R score significantly differed between groups (COM>SD>HC). While SD and COM did not differ in cross-disorder PRS and GMV, SD and COM versus HC displayed increased cross-disorder PRS and decreased GMV in the bilateral insula, the left middle temporal, the left inferior parietal, and several frontal gyri. Our results thus suggest that disorders in the affective disorders-psychosis spectrum with or without additional comorbidities differ in self-reported clinical data, but not on genetic or brain structural levels.