Women with schizophrenia frequently discontinue antipsychotic medications during pregnancy. However, evidence on the risk of postpartum relapse associated with antipsychotic use during pregnancy is lacking.

To investigate the within-individual association between antipsychotic continuation during pregnancy and postpartum relapse in women with schizophrenia.

This retrospective cohort study used data of women with schizophrenia who gave live birth between 2007 and 2018 identified from the National Health Information Database of South Korea. Women were classified according to antipsychotic use patterns during the 12 months before delivery as non-users, discontinuers and continuers. Relapse was defined as admission for psychosis (ICD-10, F20–29). The incidence rate ratio (IRR) for admission for psychosis in the 6-month postpartum period was estimated using conditional Poisson regression, with the reference period set between 2 and 1 years before delivery. Additionally, we calculated the relative risk ratios (RRRs) for the IRRs of different antipsychotic use patterns.

Among the 3026 women included in the analysis (median age 34 years, interquartile range 31–37), the within-individual risk of admission for psychosis in the 6-month postpartum period was 0.56 times (RRR, 95% CI 0.36–0.87) lower in continuers (IRR = 1.31, 95% CI 0.89–1.72) than in discontinuers (IRR = 2.34, 95% CI 1.87–2.91). Among discontinuers, the IRRs of admission for psychosis in the 6-month postpartum period did not change significantly with the timing of discontinuation (trend P = 0.946).

Antipsychotic continuation during pregnancy was associated with a reduced risk of postpartum relapse in women with schizophrenia. Continuing antipsychotics during pregnancy would be recommended after a risk–benefit assessment.

Psychotic-like experiences (PLEs) are subclinical phenomena that often precede the onset of psychosis and occur in various mental disorders. Social determinants of psychosis and PLEs are important and have been operationalized within the social defeat (SD) hypothesis. The SD hypothesis posits that low social status and exposure to repeated humiliation can lead to imbalanced dopamine neuron activity, and thus increased risk of psychosis. We aimed to assess the role of dynamic interactions between SD components in shaping the occurrence of PLEs using a network analysis.

A total of 2241 non-clinical, young adults were assessed at baseline and invited for reassessment after a 6-month follow-up. Self-reports recording the occurrence of PLEs, aberrant salience (AS), depressive, and anxiety symptoms as well as SD characteristics (socioeconomic status, minority status, humiliation, perceived constraints, and domain control) were administered. Two networks were analyzed (the first one covering all baseline measures and the second one with the baseline SD components and follow-up measures of AS and psychopathology).

The SD components were not directly connected to the measures of PLEs in both networks. However, in both networks, SD components were connected to PLEs through a mediating effect of AS. Among SD components, humiliation had the highest bridge centrality across three predefined communities of variables (SD; depressive and anxiety symptoms; AS, and PLEs).

The findings indicate that SD might make individuals vulnerable to develop PLEs through the mediating effects of AS. Among SD components, humiliation might play the most important role in the development of PLEs.

Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al., 2023) and examined the impact of CT on hypothesized lower free water-corrected FA (FAT) and higher extracellular free water (FW).

Thirty-seven SZ and 129 healthy controls (HC) were grouped into the ‘none/low’ or ‘high’ CT group. All participants underwent diffusion-weighted magnetic resonance imaging. We performed tract-based spatial statistics to study the main effects of diagnostic group and CT, and the interaction between CT and diagnostic group across FAT and FW.

SZ displayed lower FAT within the corpus callosum and corona radiata compared to HC (p < 0.05, Threshold-Free Cluster Enhancement (TFCE)). Independent of diagnosis, we observed lower FAT (p < 0.05, TFCE) and higher FW (p < 0.05, TFCE) in both SZ and HC with high CT levels compared to SZ and HC with none or low CT levels. Furthermore, we did not identify an interaction between CT and diagnostic group (p > 0.05, TFCE).

These novel findings suggest that the impact of CT on lower FAT may reflect cellular rather than extracellular alterations in established schizophrenia. This highlights the impact of CT on white matter microstructure, regardless of diagnostic status.

The objective of the current research is to study the serum levels of ischemia modified albumin (IMA), a new oxidative stress indicator, and various peptides (galanin, alarin, and meteorin-like protein) that may affect the pathophysiology of schizophrenia, determine their relationship with clinical features and each other, and compare them to those in healthy controls.

This is a cross-sectional study consisting of 45 individuals with schizophrenia who are in remission and 45 healthy individuals. The differences and relationships between categorical variables and serum protein levels of the patient and control groups were statistically analysed. Receiver operating characteristics analysis was used for the diagnostic decision-making properties of serum protein levels to predict the presence of the disease.

In comparison with the control group, the median levels of serum proteins galanin and alarin were statistically lower in the patient group, whereas METRNL and IMA levels were higher. Considering the predictive values of serum proteins in the diagnosis of the disease, it was observed that serum galanin, alarin, and IMA levels had a sensitivity and specificity higher than 80%, followed by METRNL with 73.3% sensitivity and 66.7% specificity.

Our findings reveal galanin, alarin, meteorin-like protein, and IMA are important molecules with high sensitivity and specificity in diagnosing schizophrenia. Furthermore, we think that further studies are needed to use them as reliable parameters in terms of clinical course, classification, and prognosis in explaining the etiopathogenesis of the disease.

Cognitive behavioural therapy (CBT) is one of the best-evidenced psychosocial interventions for psychosis and is recommended by the National Institute for Health and Care Excellence and the American Psychiatric Association. CBT was developed and derived from Western cultural values, which may not be appropriate for non-Western cultures. Trials of CBT in Western countries have indicated that participants from ethnic minority groups demonstrate low rates of engagement, retention, and recruitment. This indicates that the principles underlying CBT may conflict with individual beliefs and cultural values in non-Western countries. Therefore, we interviewed 15 people diagnosed with schizophrenia and 15 with their family members to explore the beliefs and attitudes of people diagnosed with schizophrenia and their family members concerning the proposed CBT intervention for psychosis in the Saudi context. The findings revealed that most participants accepted the proposed intervention. Important factors that influenced participants’ engagement and motivation in the CBT intervention were related to the therapist’s qualities (sex, empathy, and competence), family involvement, religion, and the number and format of CBT sessions for psychosis.

1. (1) To explore the beliefs and attitudes of people diagnosed with schizophrenia concerning the proposed CBT intervention for psychosis and how to improve it to make it more appropriate for their needs and cultures.

2. (2) To explore the beliefs and attitudes of family members of people diagnosed with schizophrenia concerning the proposed CBT intervention for psychosis and how to improve it to make it more appropriate to their needs and culture.

Previous economic evidence about interventions for schizophrenia is outdated, non-transparent and/or limited to a specific clinical context.

We developed a de novo discrete event simulation (DES) model for estimating the cost-effectiveness of interventions in schizophrenia in the UK.

The DES model was developed based on the structure of previous models, populated with demographic, clinical and cost data from the UK, and antipsychotics' effects from recent network meta-analyses. We simulated treatment pathways for patients with first-episode schizophrenia including events such as relapse, remission, treatment discontinuation, cardiovascular disease and death and estimated costs (2020£) taking the National Health Service perspective and quality-adjusted life years (QALYs) over ten years. Using the model, we ranked ten first-line antipsychotics based on their QALYs and cost-effectiveness.

Amisulpride was associated with the highest QALYs, followed by risperidone long-acting injection (LAI), aripiprazole-LAI (6.121, 6.084, 6.070, respectively) and others (5.947–6.058). The most cost-effective antipsychotics were amisulpride, olanzapine and risperidone-LAI, with total probability of rankings of 1, ≤2, ≤3, that is, 95%, 89%, 80%, respectively; meanwhile, the least cost-effective were cariprazine, lurasidone and quetiapine, with total probability of rankings of 10, ≥9, ≥8, that is, 96%, 92%, 81%, respectively. Results were robust across sensitivity analyses and influenced primarily by relapse relevant parameters.

Our findings suggest amisulpride (or risperidone-LAI where oral treatment is inappropriate) as the best overall first-line option based on QALYs and cost-effectiveness. Our ranking may be used to guide decision-making between antipsychotics. Our model is open source and could be applied to the other settings.

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

While omega-3 polyunsaturated fatty acids (PUFAs) have shown promise as an adjunctive treatment for schizophrenia and other psychotic disorders, the overall consensus about their efficacy across studies is still lacking and findings to date are inconclusive. No clinical trials or systematic reviews have yet examined if omega-3 PUFAs are associated with differential levels of efficacy at various stages of psychosis.

A systematic bibliographic search of randomized double-blind placebo-controlled trials (RCTs) examining the effect of omega-3 PUFAs as a monotherapy or adjunctive therapy versus a control group in adults and children at ultra-high risk (UHR) for psychosis, experiencing a first-episode psychosis (FEP), or diagnosed with an established psychotic disorder was conducted. Participants’ clinical symptoms were evaluated using total and subscale scores on validated psychometric scales.

No beneficial effect of omega-3 PUFAs treatment was found in comparison with that of placebo (G = −0.26, 95% CI −0.55 to 0.03, p = 0.08). Treatment of omega-3 PUFAs did not prove any significant improvement in psychopathology in UHR (G = −0.09, 95% CI −0.45 to 0.27, p = 0.63), FEP (G = −1.20, 95% CI −5.63 to 3.22, p = 0.59), or schizophrenia patients (G = −0.17, 95% CI −0.38 to −0.03, p = 0.10).

These findings confirm previous evidence that disputes the original reported findings of the beneficial effect of omega-3 PUFAs in schizophrenia. Furthermore, accumulative evidence of the use of omega-3 as a preventive treatment option in UHR is not supported, suggesting that the need for future studies in this line of research should not be promoted.

Emerging evidence suggests a potential association between “leaky gut syndrome” and low-grade systemic inflammation in individuals with psychiatric disorders, such as schizophrenia. Gut dysbiosis could increase intestinal permeability, allowing the passage of toxins and bacteria into the systemic circulation, subsequently triggering immune-reactive responses. This study delves into understanding the relationship between plasma markers of intestinal permeability and symptom severity in schizophrenia. Furthermore, the influence of lifestyle habits on these intestinal permeability markers was determined.

Biomarkers of intestinal permeability, namely lipopolysaccharide-binding protein (LBP), lipopolysaccharides (LPS), and intestinal fatty acid binding protein (I-FABP), were analyzed in 242 adult schizophrenia patients enrolled in an observational, cross-sectional, multicenter study from four centers in Spain (PI17/00246). Sociodemographic and clinical data were collected, including psychoactive drug use, lifestyle habits, the Positive and Negative Syndrome Scale to evaluate schizophrenia symptom severity, and the Screen for Cognitive Impairment in Psychiatry to assess cognitive performance.

Results revealed elevated levels of LBP and LPS in a significant proportion of patients with schizophrenia (62% and 25.6%, respectively). However, no statistically significant correlation was observed between these biomarkers and the overall clinical severity of psychotic symptoms or cognitive performance, once confounding variables were controlled for. Interestingly, adherence to a Mediterranean diet was negatively correlated with I-FABP levels (beta = −0.186, t = −2.325, p = 0.021), suggesting a potential positive influence on intestinal barrier function.

These findings underscore the importance of addressing dietary habits and promoting a healthy lifestyle in individuals with schizophrenia, with potential implications for both physical and psychopathological aspects of the disorder.

Neuroimaging studies have documented brain structural changes in schizophrenia at different stages of the illness, including clinical high-risk (cHR), genetic high-risk (gHR), first-episode schizophrenia (FES), and chronic schizophrenia (ChS). There is growing awareness that neuropathological processes associated with a disease fail to map to a specific brain region but do map to a specific brain network. We sought to investigate brain structural damage networks across different stages of schizophrenia.

We initially identified gray matter alterations in 523 cHR, 855 gHR, 2162 FES, and 2640 ChS individuals relative to 6963 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to four specific networks.

Brain structural damage networks of cHR and gHR had limited and non-overlapping spatial distributions, with the former mainly involving the frontoparietal network and the latter principally implicating the subcortical network, indicative of distinct neuropathological mechanisms underlying cHR and gHR. By contrast, brain structural damage networks of FES and ChS manifested as similar patterns of widespread brain areas predominantly involving the somatomotor, ventral attention, and subcortical networks, suggesting an emergence of more prominent brain structural abnormalities with illness onset that have trait-like stability over time.

Our findings may not only provide a refined picture of schizophrenia neuropathology from a network perspective, but also potentially contribute to more targeted and effective intervention strategies for individuals at different schizophrenia stages.

The lifetime prevalence of suicide is around 5% in patients with schizophrenia. Non-adherence to antipsychotic medication is an important risk factor, but prospective studies investigating joint effects of antipsychotic drugs, antidepressants, and benzodiazepines on suicidality are scarce. We aimed to investigate how use and non-use of psychotropic medications are associated with suicidality in schizophrenia.

An open cohort study followed all patients consecutively admitted to a psychiatric acute unit during a 10-year period with a diagnosis of schizophrenia (n = 696). Cox multiple regression analyses were conducted with use of antipsychotics, antidepressants, and benzodiazepines as time-dependent variables. Adjustments were made for age, gender, depressive mood, agitated behavior, and use of alcohol and illicit substances.

A total of 32 (4.6%) suicide events were registered during follow-up. Of these, 9 (28%) were completed suicides and 23 (72%) were attempted suicides. A total of 59 (8.5%) patients were readmitted with suicidal plans during the follow-up. Compared to non-use, use of antipsychotics was associated with 70% lower risk of attempted or completed suicide (adjusted hazard ratio [AHR] = 0.30, p < 0.01, CI 0.14–0.65) and 69% reduced risk of readmission with suicidal plans (AHR = 0.31, p < 0.01, CI 0.18–0.55). Use of prescribed benzodiazepines was associated with 126% increased risk of readmission with suicidal plans (AHR = 2.26, p = 0.01, CI 1.24–4.13).

Adherence to antipsychotic medication is strongly associated with reduced suicidal risk in schizophrenia. The use of prescribed benzodiazepines was identified as a significant risk factor for being readmitted with suicidal plans.

Suicide accounts for a proportion of the early mortality in people affected by psychotic disorders. The early phase of illness can represent a particularly high-risk time for suicide. Therefore, in a cohort of young people presenting with first-episode psychosis, this study aimed to determine: (i) the prevalence of suicidal ideation, intent with plan and self-harm and any associated demographic or clinical factors and (ii) the prevalence of depressive symptoms and any associated demographic or clinical factors.

Young people with a first episode of psychosis attending the Early Psychosis Prevention and Intervention Centre in Melbourne were included. Suicidal behaviours were recorded using a structured risk assessment – ‘Clinical Risk Assessment and Management in the Community’, and depressive symptoms were measured using the PHQ-9.

A total of 355 young people were included in the study. 57.2% were male, 95.4% were single and over one quarter were migrants. At the time of presentation, 34.6% had suicidal ideation, 6.2% had suicidal intent with a plan, and 21.4% had engaged in self-harm before their presentation. Combined, 39.7% (n = 141) presented with suicidal ideation, intent with plan or self-harm. A total of 71.5% (n = 118) had moderately severe or severe depressive symptoms, which was strongly associated with suicidal ideation or behaviours at the time of presentation (OR = 4.21, 95% C.I. 2.10–8.44).

Depressive symptoms, self-harm and suicidal behaviours are commonly present in the early phases of a psychotic disorder, which has important clinical implications for assessment and management.