The combination of antidepressant and antipsychotic medication is an effective treatment for major depressive disorder with psychotic features ('psychotic depression'). The present study aims to identify sociodemographic and clinical predictors of remission of psychotic depression treated with combination pharmacotherapy and determine the accuracy of prediction models.

Two hundred and sixty-nine participants aged 18 to 85 years with psychotic depression were acutely treated with protocolized sertraline plus olanzapine for up to 12 weeks. Three cross-validated machine learning models were implemented to predict remission based on 74 sociodemographic and clinical variables measured at acute baseline. The optimal model for each method was selected by the average fold C-index. Based on the performance of each method, grouped elastic net (cox) regression was chosen to examine the association of each predictor with remission of psychotic depression.

Of the 269 participants, 145 (53.9 %) experienced full remission of the depressive episode and psychotic features. Multivariable models had 65.1 % to 67.4 % accuracy in predicting remission. In the grouped elastic net (cox) regression model, longer duration of index episode, somatic or tactile hallucinations, higher burden of comorbid physical problems, and single or divorced marital status were independent predictors of longer time to remission. A higher number of lifetime depressive episodes and peripheral vascular or cardiovascular disease were predictors of shorter time to remission.

Future research needs to determine whether the addition of biomarkers to clinical and sociodemographic variables can improve model accuracy in predicting remission of pharmacologically-treated psychotic depression.

Schizophrenia is a severe yet treatable mental disorder, and it is diagnosed using a multitude of primary and secondary symptoms. Diagnosis and treatment for each individual depends on the severity of the symptoms. Therefore, there is a need for accurate, personalised assessments. However, the process can be both time-consuming and subjective; hence, there is a motivation to explore automated methods that can offer consistent diagnosis and precise symptom assessments, thereby complementing the work of healthcare practitioners. Machine Learning has demonstrated impressive capabilities across numerous domains, including medicine; the use of Machine Learning in patient assessment holds great promise for healthcare professionals and patients alike, as it can lead to more consistent and accurate symptom estimation. This survey reviews methodologies utilising Machine Learning for diagnosing and assessing schizophrenia. Contrary to previous reviews that primarily focused on binary classification, this work recognises the complexity of the condition and, instead, offers an overview of Machine Learning methods designed for fine-grained symptom estimation. We cover multiple modalities, namely Medical Imaging, Electroencephalograms and Audio-Visual, as the illness symptoms can manifest in a patient's pathology and behaviour. Finally, we analyse the datasets and methodologies used in the studies and identify trends, gaps, as opportunities for future research.

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in blood- and brain-based materials. From the studies that had validated the preliminary findings, potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p, -30d-5p, -330-5p, -378a-5p, -21-3p, -330-3p, -345-5p in whole blood, miR-19b-3p, -1180-3p, -125a-5p, let-7e-5p in blood plasma, and miR-7-5p, -23b-5p, -142-3p, -221-5p, -370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptor-site binders (drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics (drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and -29c with miR-30e-3p and -526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p, -29a-3p, -106a-5p, -106b-5p, -107, -125a-3p, -125b-5p and of miR-107, -125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p, -107 was found for manic compared to euthymic patients. In two other studies using blood plasma, downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134, -152, -607, -633, -652, -155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a, -34b, -34c, -137, and -140-3p, -21-3p, -30d-5p, -330-5p, -378a-5p, -134, -19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.

Obsessive-compulsive disorder (OCD) and psychosis frequently co-occur, with several hypotheses proposed to explain the relationship between them, and there is limited information regarding the comorbidity of OCD and psychotic symptoms. Therefore, we aimed to detect the prevalence of psychotic symptoms in OCD patients and analyze the psychopathological and neuroimaging associations using Diffuse Tensor Imaging (DTI) between OCD with and without psychotic symptoms in a subset of these patients. Initially, 100 subjects with OCD were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) and a subset of 60 subjects underwent neuroimaging using DTI. Out of 100 subjects, 39 % were classified as OCD with psychotic features, who differed significantly from non-psychotic OCD on several Y-BOCS, BPRS and DTI (especially volume) domains. Our study suggests several clinical and neuroradiological (using DTI) differences between OCD with and without psychotic features. Clinically, the OCD group with psychotic symptoms had a shorter duration of illness, fewer previous episodes and a poorer level of insight, while on DTI, they had significant reduction in grey matter (GM) volume across several brain regions, and significant reduction in the right hippocampal tract on mean diffusivity (MD).

It is unclear if lithium and quetiapine have neuroprotective effects, especially in early stages of bipolar and schizoaffective disorders. Here, an age-related multivariate brain structural measure (i.e., brain-PAD) at baseline and changes in response to treatment after a first-episode mania (FEM) were examined. FEM participants were randomized to lithium (n=21) or quetiapine (n=18) monotherapy. T1-weighted scans were acquired at baseline, 3-months (FEM participants only) and 12-months. Brain age predictions for healthy controls (n=29) and young people with bipolar or schizoaffective disorder (15-25 years) were derived using a deep learning model trained on one of the largest datasets (N=53,542) to date. Notably, a higher brain-PAD value (predicted brain age - age) signifies an older-appearing brain. Baseline brain-PAD was higher in young people with FEM compared to controls (+1.70 year, p=0.04; Cohen's d=0.53 [SE=0.25], CI 95% [0.04 to 1.01]). However, no significant effects of time or treatment group, nor an interaction between the two, were observed throughout the course of the study. Baseline brain-PAD did not predict any change in symptomatic, quality of life or functional outcome scores over 12 months. In young individuals with FEM, baseline findings show their brains appeared older than controls. However, brain-PAD remained stable over time across treatment groups and neither baseline values nor treatment predicted 12-month outcomes. A longer follow-up with a larger sample is warranted to determine if treatment effects emerge later in bipolar and schizoaffective disorders. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.

While circadian disruptions are common in some sub-groups of youth with mood disorders, skin temperature rhythms in these cohorts are understudied. We examined 24-h wrist skin temperature rhythms in youth with emerging mood disorders, exploring associations with clinical stage and proposed illness subtypes. Youth (n = 306, 23.42 ± 4.91 years, 65% females) accessing mental health care and 48 healthy controls (23.44 ± 3.38 years, 60% females) were examined. Skin temperature parameters including rhythm-adjusted mean temperature, inter-daily stability (day-to-day consistency), intra-daily variability (rhythm fragmentation), and peak temperature time were derived from a wearable sensor. Based on our illness trajectory-pathophysiology model, participants were classified by mood disorder subtypes ("hyperarousal-anxious" [n = 209], "neurodevelopmental-psychosis" [n = 40], or "circadian-bipolar spectrum" [n = 43]), as well as by clinical stage (subthreshold disorders classed as 1a or 1b [n = 47, 173, respectively], and full-threshold disorders as 2+ [n = 76]). Compared to controls, youth with mood disorders had delayed, less stable, and more variable skin temperature rhythms, indicated by lower rhythm-adjusted mean skin temperature (29.94 ± 0.10 °C vs 31.04 ± 0.25 °C, p < 0.001), delayed peak timing (0533 ± 0014 vs 0332 ± 0036, p = 0.002), reduced inter-daily stability (p = 0.009), and increased intra-daily variability (p = 0.020). Peak skin temperature also occurred later relative to sleep midpoint (0.31 ± 0.14 vs -0.48 ± 0.35 radians, p = 0.037). The "circadian-bipolar spectrum" subtype exhibited lower relative amplitude (0.07 ± 0.005 vs 0.08 ± 0.002 [hyperarousal-anxious] and 0.09 ± 0.005 [neurodevelopmental-psychosis], p = 0.039), with no delay in sleep midpoint. Clinical stages were not associated with differences in skin temperature parameters. These findings highlight the potential of use of 24-h skin temperature rhythms as a non-invasive biomarker of circadian disturbances in youth with emerging mood disorders. The observed disruptions in temperature patterns and rhythmicity support the notion that disrupted circadian rhythms may mediate the onset or illness course of some subgroups of youth with emerging major mood disorders.

Our previous studies showed that dexamphetamine, an indirect dopamine agonist, widens Stimulus Binding Windows (BWs) in healthy subjects. The present study aimed to investigate the effect of nabilone, a synthetic cannabinoid agonist, on the BWs in a unimodal illusion: the tactile funneling illusion (TFI). The study also aimed to study the association between tactile illusion with psychometric scores. Healthy participants (n = 32) completed the TFI at various delays and distances of separation of stimuli after receiving nabilone (2-4 mg, PO) or placebo in a randomized, double-blind, counterbalanced, crossover manner. The primary illusory measures were funneling and errors of localisation (EL). Three physiological and five psychometric measurements were also performed. The results showed that nabilone decreased funneling in a delay-dependent manner (p = 0.0016), whereby funneling was reduced at 0 ms (p = 0.01). Nabilone also significantly reduced EL in a distance-dependent manner (p = 0.038). Nabilone increased ratings on two of the five administered psychometric scales (p < 0.05), without significantly changing the overall (average) scores. However, there were associations between the overall psychometric scores and funneling under the strongest (0 ms delay) illusion condition, which is dependent on the drug condition (nabilone ρ = 0.45, p = 0.028). To conclude, unlike the effects of dexamphetamine, low activation of the cannabinoid system decreases the illusory perception of funneling, with narrowing spatial BWs.

Schizophrenia and schizophrenia-type psychosis, severe mental illnesses globally impacting millions, present a dual challenge with their characteristic positive and negative symptoms, economic burdens, and heightened susceptibility to coercive measures. These measures, including seclusion and restraint, raise ethical concerns despite their intent to ensure safety, particularly during acute stages marked by violent behaviour. Addressing this backdrop, the significance of post-incident debriefing as an intervention to curtail the use and duration of coercive measures and alleviate the negative psychological effects of using these methods in managing individuals with schizophrenia is underscored. The employment of coercive measures, such as physical restraint and seclusion, to manage aggressive behaviour in psychiatric settings necessitates a thorough examination of their ethical implications and potential psychological harm. Although post-incident debriefing is recommended, the limited evidence supporting its efficacy and concerns about its impact on psychological well-being prompt a comprehensive analysis of existing literature.

To investigate the effects of post-incident debriefing after coercive measures for people with schizophrenia or schizophrenia-type psychosis.

The Information Specialist conducted searches of the Cochrane Schizophrenia Specialised Register (compiled from searches of CENTRAL, MEDLINE, Embase, PubMed, CINAHL, PsycINFO, ClinicalTrials.gov, WHO ICTRP, ISRCTN, ProQuest Dissertations and Theses A&I) on 28 February 2023. We also inspected the references of all identified studies.

We included all randomised controlled trials (RCTs) of post-incident debriefing after coercive measures in adult psychiatric care with participants diagnosed with schizophrenia or schizophrenia-type psychosis, encompassing various clinical states and stages. We considered studies if the post-incident debriefing was the only intervention randomised.

At least two authors inspected the citations, selected studies, extracted data and conducted quality appraisal. We calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) for binary outcomes and the mean difference (MD) with 95% CI for continuous outcomes. We assessed study risk of bias and used the GRADE approach to create a summary of findings table.

We included one study; the total number of participants randomised was 422, of which 109 participated. Participants were between 18 and 65 years old with psychotic disorder, at the acute stage of their illness, and had experienced at least one coercive measure during their hospital stay. The study included a standardised post-coercion review that was conducted until the discharge of the participant. For the primary outcome, we found that there may be an increased risk of being secluded again for those receiving post-incident debriefing compared to treatment as usual, but the evidence is very uncertain (RR 1.32, 95% CI 0.74 to 2.33; 1 study, 109 participants; very low-certainty evidence). No evidence was found that post-incident debriefing had an effect in reducing peritraumatic distress (MD -1.62, 95% CI -7.47 to 4.23; 1 study, 82 participants; very low-certainty evidence) or increasing satisfaction with care (perceived coercion: MD -0.37, 95% CI -1.59 to 0.85; 1 study, 109 participants; coercion experience: MD -1.61, 95% CI -13.36 to 10.14; 1 study, 109 participants; very low-certainty evidence) compared to treatment as usual. The evidence is very uncertain about the effect of post-incident debriefing on these outcomes. No usable data were available for change in patient behaviour or adverse effects.

Considering the available evidence, it is not possible to arrive at definitive conclusions that post-incident debriefing after coercive measures is effective for people with schizophrenia or schizophrenia-type psychosis. Further high-quality studies are warranted to evaluate the effects of post-incident debriefing in psychiatric inpatient care.

Schizophrenia is one of the most severe and costly mental disorders in terms of human suffering and societal expenditure. About 15-30% of patients do not respond to all known antipsychotics, including clozapine, the current gold standard in these cases. Electroconvulsive therapy (ECT) is well-known to be highly effective in clozapine-treatment-resistant schizophrenia (CRS), and synergistic effects of clozapine and ECT have been demonstrated. However, relapse rates after successful courses of ECT are still very high, and evidence for maintenance ECT (mECT) in CRS is scarce at best.

Here, we present the protocol of the MECT-RESIST trial, a German multi-center, observer-blind, randomized, and actively controlled parallel-group clinical trial. The scientific aim of the study is to test the hypothesis that mECT plus treatment as usual (TAU) (intervention group) is superior to TAU alone (control group) for relapse prevention in CRS. The primary endpoint is time to relapse. Secondary endpoints include the proportion of relapse-free patients, the global level of functioning and quality of life, depressive symptoms, overall symptoms of schizophrenia, concomitant catatonic symptoms, stress and self-stigmatization and cognitive performance. We aim at randomizing 84 patients between 18 and 65 years with a clinically diagnosed CRS and brief psychotic rating scale (BPRS) > 45, who responded to a series of ECT (BPRS < 70% of initial BPRS), to either recieve mECT + TAU or TAU over a period of 28 weeks followed by a follow-up of 12 months. The study will be performed between 2025 and 2028.

In this multi-center trial, we aim to examine the effectiveness of mECT in CRS patients who improved after a course of routine ECT. If mECT will lead to a longer time to relapse and/or to a higher proportion of relapse-free patients compared to those undergoing treatment as usual, this trial would have an enormous impact on therapeutic strategies for patients with CRS and would induce a profound change of current treatment guidelines, where ECT still ranks at the level of ultima ratio, despite accumulating evidence suggesting otherwise.

ClincalTrials.gov NCT06456983, registered 7 Jun 2024. Deutsches Register Klinischer Studien DRKS00036886, registered 14 May 2025.

We investigated alterations in impulsive choice and impulsive action among individuals with methamphetamine use disorder (MUD) compared to a control group after exposure to cues associated with methamphetamine (METH).

Thirty-four participants with MUD and 31 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment and to perform the go/no-go task as well as the balloon analog risk task (BART) before (the baseline condition) and after (the cue-induced condition) watching a VR video.

There were no significant differences between groups for go/no-go task both in the baseline condition and cue-induced condition. The METH group exhibited more adjusted pumps in the cue-induced condition than in the baseline condition. The λ (loss aversion) of the METH group was significantly lower in the cue-induced condition than in the baseline condition. In the correlation analysis of behavioral data and the exponential-weight mean-variance (EWMV) parameters, λ was the only parameter related to adjusted pumps both in the baseline condition and the cue-induced condition, reflected by a strong negative correlation.

These findings suggest that METH related cues may impact impulsive choice, but not impulsive action, by decreasing loss aversion.

Cognitive impairment, a key feature of psychosis, is linked to poor functional outcomes. This study aimed to identify predictors and outcomes associated with cognitive decline in psychotic disorders.

Data were taken from the Suffolk County Mental Health Project, a first-admission longitudinal cohort study of individuals with psychotic disorders. Participants were recruited from all 12 inpatient psychiatric facilities in Suffolk County, New York. Cognitive function was assessed at 6-month, 24-month, 20-year, and 25-year follow-ups. This analysis includes 400 participants with at least 2 estimates of general cognitive ability. A mixed effects model with random slopes and random intercepts was employed to estimate individual cognitive trajectories. The estimated random slopes for each participant were then used to predict 25-year clinical outcomes.

No baseline predictors of subsequent cognitive decline were identified. Faster cognitive decline was associated with lower odds of remission, recovery, employment, financial independence, and worse social function 25 years after first admission.

Cognitive decline may be an indicator of illness severity more broadly and may therefore be a useful indicator of who might benefit from known interventions targeting clinical outcomes. Intervening in cognitive decline itself may have widespread beneficial effects on outcomes in psychotic disorders.

Clinical course after first episode psychosis (FEP) is heterogeneous. Subgrouping and predicting longitudinal symptom trajectories after FEP may help develop personalized treatment approaches. We utilized k-means clustering to identify clusters of 411 FEP patients based on longitudinal positive and negative symptoms. Three clusters were identified. Cluster 1 exhibits lower positive and negative symptoms (LS), lower antipsychotic dose, and relatively higher affective psychosis; Cluster 2 shows lower positive symptoms, persistent negative symptoms (LPPN), and intermediate antipsychotic doses; Cluster 3 presents persistently high levels of both positive and negative symptoms (PPNS), and higher antipsychotic doses. We predicted cluster membership (AUC of 0.74) using ridge logistic regression on baseline data. Key predictors included lower levels of apathy, affective flattening, and anhedonia/asociality in the LS cluster, compared to the LPPN cluster. Hallucination severity, positive thought disorder and manic hostility predicted PPNS. These results help parse the FEP trajectory heterogeneity and may facilitate the development of personalized treatments.

Psychotic major depression (PMD) differs from non-psychotic MD (NPMD) in psychopathology and is linked to changes in brain volumetry and hypothalamic-pituitary-adrenal (HPA) axis function that can be reflected by its principal output - the glucocorticoid cortisol. NPMD patients exhibit smaller hippocampi than healthy controls (HC), purportedly representing exposure to chronic stress. However, the relationship between the individual clinical phenotype, hippocampal volume and diurnal cortisol signaling remains unclear.

Since understanding the interplay among symptoms, neuroimaging and HPA function is crucial for discerning biological differences between PMD and NPMD, this study explored the link between clinical phenotype, hippocampal structural MRI and circadian plasma cortisol levels in 32 HC, 27 NPMD and 26 PMD patients.

PMD patients showed significantly elevated evening (6 p.m. - 1 a.m.) cortisol levels compared to NPMD and HC, while NPMD and HC did not differ. No group differences in hippocampal volume were observed, but a significant interaction effect emerged between overnight (1 a.m. - 9 a.m.) cortisol levels, hippocampal volume, and clinical phenotype. NPMD patients displayed a negative correlation between overnight cortisol levels and hippocampal volume, which was specific to the ascending cortisol curve (2 a.m. - 5 a.m.) and absent in PMD and HC. The hippocampus-cortisol interaction was associated with depressive symptom severity in NPMD but not PMD, where cortisol alone predicted greater severity.

These findings imply a time-dependent relationship between hippocampal volume and overnight cortisol in NPMD, which is absent in PMD and HC. In contrast, PMD patients exhibited increased evening cortisol levels. In an exploratory analysis, these effects were also related to symptom severity at similar timepoints. While correlational, these results point to distinct neurobiological mechanisms underlying NPMD and PMD, which are potentially related to the heterogeneous clinical manifestations.

Depression is often accompanied by high levels of smoking behavior, and smoking can act as a risk factor for depression. However, there is limited neuroimaging evidence regarding the association between depression and smoking, especially the impact of this association on the brain stability remains unclear. Therefore, this study aimed to assess the interaction effect between smoking and depression from a neurodynamic perspective.

We assessed the resting-state functional magnetic resonance imaging from 193 participants (55 depressed smokers; 51 depressed non-smokers; 25 healthy smokers; 62 healthy non-smokers) and calculated 3 regional activity dynamic indicators, including dynamic regional homogeneity (dReHo), dynamic amplitude of low-frequency fluctuations (dALFF), and dynamic fractional ALFF (dfALFF). Principal component analysis was conducted on these 3 dynamic indicators, and the first component was extracted for the subsequent 2 × 2 factor designs statistical analysis.

We observed the interaction between smoking and depression increases the instability of regional activity in the precentral gyrus and precuneus. Compared with HCs, patients with depression showed increased instability of regional activity across widespread regions such as the precentral gyrus, thalamus, and medial frontal gyrus. No main effects of smoking were observed. In depressed smokers, the instability of regional activity in left precuneus is positively correlated with anxiety symptoms.

Our findings indicate that smoking potentially exacerbates brain abnormal instability in depression, implying a clinical need to require patients with depression to abstain from smoking.

Electronic health records (EHR) passively generate large datasets on real-world patient populations in easily retrievable form, allowing the cost-efficient and timely execution of epidemiological cohorts on a broad array of topics. However, EHR-based cohorts specialising in mental disorders have not yet been reported. Ningbo has made significant achievements in healthcare data management in China. This study, relying on the Ningbo Mental Health Information System and the Ningbo Regional Health Information Platform, has established the Ningbo Schizophrenia Cohort (NSC), providing an exemplary study for cohort studies on schizophrenia.

This population-based ambispective cohort study included patients with schizophrenia aged 18-65 years at the time of diagnosis who were eligible for healthcare services in Ningbo, China. Participants were identified using the Ningbo Mental Health Information System between 1 January 2010, and 31 December 2023. Once an individual enters the NSC, they are followed up continuously until death or relocation. A total of 26 899 patients with schizophrenia are included in the NSC.

Among 26 899 patients, 55.4% were female and 53.1% had less than 7 years of education. Until 31 December 2023, 4505 deaths occurred, and 97.83% of patients had at least one electronic medical record. The median age at diagnosis for non-survivors (median (IQR): 40 (29-51) years) was higher than that of survivors (median (IQR): 34 (26-45) years).

The NSC will continue to collect longitudinal data to capture the full life cycle of schizophrenia, including pre-onset, diagnosis, follow-up, recovery or death. This will result in a continuous, complete and multidimensional EHR for patients with schizophrenia. Planned future research aims to generate new real-world evidence on the aetiology of schizophrenia, investigate comorbidities to facilitate co-management and develop predictive models for schizophrenia and related cardiovascular diseases.

NCT06370793.

Type 2 diabetes mellitus (T2DM) and impaired glucose metabolism are more prevalent among patients with schizophrenia than in the general population. The incidence of T2DM is associated with lifestyle factors that are often influenced by the negative symptoms of schizophrenia; comorbid T2DM may contribute to the reduced life expectancy observed in patients with schizophrenia. The existing literature reveals a scarcity of data regarding the potential causal relationship between T2DM and negative symptoms.

A scoping review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria, utilizing the PubMed database to identify clinical studies investigating the association between T2DM and the negative (but not cognitive) symptom domain of schizophrenia. Subsequently, the reference lists of these identified publications were searched.

Seventeen publications were included. There is evidence supporting the association between impaired glucose tolerance and increased negative symptoms in patients with first-episode psychosis, and several studies indicate that poorer glucose metabolic status correlates with more severe negative symptoms. Patients with T2DM and chronic schizophrenia, however, had milder negative symptom scores compared to those without diabetes, although this association was less pronounced than in early disease stages.

There is insufficient confirmatory evidence regarding the potential causality of T2DM on the negative symptoms of schizophrenia. Further, preferably prospective studies are needed to explore the complex and potentially causal relationship between T2DM and negative symptoms of schizophrenia. If T2DM were found to have a causal relationship with negative symptoms or to exacerbate pre-existing symptoms, it could lead to significant changes in therapeutic approaches for schizophrenia.

Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations, calculations weighing the costs vs. the benefits of actions. Several reports have shown that people with schizophrenia display a reduced willingness to exert effort for monetary rewards when compared to controls. The primary goal of the current study was to further characterize reduced willingness to exert effort in schizophrenia by determining whether reduced willingness reflects (1) reduced sensitivity to reward, (2) increased sensitivity to effort, or (3) a combination of both.

We assessed effort-cost decision-making in 30 controls and 30 people with schizophrenia, using 2 separate experimental tasks. Critically, one paradigm allowed for independent estimation of effects of reward and effort sensitivity on choice behavior. The other task isolated effort sensitivity by measuring effort in the absence of reward. Clinical interviews and self-report questionnaires were administered to people with schizophrenia to determine negative symptom severity.

Across both tasks, we found evidence for reduced willingness to exert effort in people with schizophrenia compared to controls. Further, in both paradigms reduced willingness to exert effort was driven by increased sensitivity to effort in people with schizophrenia compared to controls. In contrast, measures of reward sensitivity did not significantly differ between groups. Surprisingly, we did not find correlations between task variables and measures of negative symptom severity.

These findings further specify prior work by identifying a specific contributory role for increased effort sensitivity in effort-cost decision-making deficits in schizophrenia.

Discharge from early psychosis intervention is a critical stage of treatment that may occur for a variety of reasons. This study characterizes reasons for discharge among participants in early psychosis intervention programs participating in the Early Psychosis Intervention Network (EPINET) which comprises >100 programs in the United States organized under 8 academic hubs.

We analyzed 1787 discharges, focusing on program completion, unilateral termination by the client/family, and lost contact with the client/family. We performed exploratory analyses of demographic, clinical, and functional predictors of discharge reason. Variables predictive of discharge type were included in multilevel logistic regressions, allowing for the estimation of predictors of discharge reason and variability in rates by program and hub.

An estimated 20%-30% of enrolled patients completed the program. Program completion rates were higher among participants who were older on admission, had lower negative symptoms severity, spent more time in education, employment, or training, and who were covered by private insurance (a close proxy for socioeconomic status). Programs were more likely to lose contact with male participants, Black participants, and participants who were never covered by private insurance. After accounting for patient-level factors, there was substantial program-level variation in all 3 discharge outcomes, and hub-level variability in the proportion of participants who completed the program. The impact of race on program completion varied substantially by program.

Participants were discharged from early psychosis intervention services for diverse reasons, some of which were associated with sociocultural factors. Disengagement is a widespread problem affecting all hubs.

The Psychodynamic Intervention Rating Scale (PIRS) stands out as one of the most widely utilised coding systems aimed at categorising micro-process from psychotherapeutic dialogue due to its feasibility and adherence to the expressive-supportive continuum. Despite this, no comprehensive analysis of its application in the literature has been published. This systematic review aims to examine the state of the art, strengths, limitations and future perspectives of such a coding tool for verbatim transcripts.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search in databases (PsycINFO, Scopus, PubMed and Web of Science) covering publications from the PIRS's first occurrence in the scientific literature in 1992 to 2024 yielded 22 publications eligible for review. Three independent reviewers screened the studies and extracted data regarding PIRS applications and key findings.

The studies examined revealed that PIRS can reliably classify interventions across various therapeutic approaches, surpassing its psychodynamic origins. It demonstrated peculiar efficacy in understanding therapeutic alliance mechanisms and patients' responses according to their typical defensive patterns. However, the findings also indicated some limitations concerning the breadth of PIRS categories, which may overlook the essential nuances of micro-processes.

While the PIRS has proven its value for understanding clinical micro-process, its categories may be slightly refined. A proposal for a more granular classification of PIRS categories has finally been provided via a literature analysis.

In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM).

An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery-Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM.

The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21-1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66-25.32).

This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Treatment engagement for individuals with psychotic disorders is often low, and engagement is considered critical to improving outcomes and reducing chronicity of the illness. Lack of insight in psychosis has been associated with poor treatment engagement and is considered a core feature of psychotic disorders. One factor that may improve treatment engagement in psychosis, perhaps for individuals with low insight, is social support. Social support may improve treatment engagement by promoting insight or overriding the challenges of engagement related to insight, however, the relationships between insight, social support, and treatment engagement are not clear. The current study hypothesized that greater insight and social support would result in better treatment engagement, and that greater social support would enhance treatment engagement for individuals with low insight. Sixty-eight (N = 68) participants with a psychotic disorder completed clinical interview and self-report measures. A relationship between insight and treatment engagement was not found, thus, social support did not moderate a relationship between the two. Participants reported on multiple treatment barriers impacting treatment engagement. As such, the impact of barriers to treatment may require consideration before accurately measuring the above constructs.

Background and Objectives: The Oppel-Kundt (O-K) geometric optical illusion has been studied among people with mental disorders to understand the differences in their visual perception. Earlier studies were mainly focused on patients with schizophrenia, while less is known about patients with depression and the influence of medication use. The objectives were to compare illusion manifestation for schizophrenia, depression, and to evaluate possible differences depending on drug use. Materials and Methods: The stimuli consisted of three horizontally arranged dots, which were considered as terminators specifying the ends of the reference and the test stimulus intervals. The reference interval was filled with a set of distracting dots and changed, at random, from 0 to 19. The participants were asked to place the central terminator in the middle, between the outer ones. The trial consisted of 10 different figures, and each trial was repeated 10 times. This study involved 35 patients with depression and schizophrenia spectrum disorders and a comparison group of 35 persons. Information about drug use by patients was retrieved from their medical records. Results: OK illusion manifested stronger in patients with depression compared to the other subjects. The patients who were taking benzodiazepines made greater errors evaluating OK figures than those who were not. No differences were found regarding other drug use. The limitations include a limited sample and possible interfering effects of other drugs, especially antidepressants, which have been shown to affect illusion perception. Conclusions: The OK illusion was more prominent in the patients with depression and in those who were taking benzodiazepines.

Previous studies have implicated hippocampal abnormalities in the neuropathology of psychosis spectrum disorders. Reduced hippocampal volume has been reported across all illness stages, and this atrophy has been hypothesized to be the result of glutamatergic excess. To test this hypothesis, we measured hippocampal subfield volumes and hippocampal glutamate levels in antipsychotic naïve first episode psychosis patients (FEP) and the progression of volume decline and changes in glutamate levels over a 16-week antipsychotic drug (APD) trial. We aimed to determine if subfield volumes at baseline were associated with glutamate levels, and if baseline glutamate levels were predictive of change in subfield volumes over time.

We enrolled ninety-three medication-naïve FEP participants and 80 matched healthy controls (HC). T1 and T2 weighted images and magnetic resonance spectroscopy (MRS) data from a voxel prescribed in the left hippocampus were collected from participants at baseline and after 6 and 16 weeks of APD treatment. Hippocampal subfield volumes were assessed using FreeSurfer 7.1.1., while glutamate levels were quantified using jMRUI version 6.0. Data were analyzed using linear mixed models.

We found regional subfield volume deficits in the CA1, and presubiculum in FEP at baseline, that further expanded to include the molecular and granule cell layer of the dentate gyrus (GC/ML/DG) and CA4 by week 16. Baseline hippocampal glutamate levels in FEP were not significantly different than those of HC, and there was no effect of treatment on glutamate. Glutamate levels were not related to initial subfield volumes or volume changes over 16 weeks.

We report a progressive loss of hippocampal subfield volumes over a period of 16 weeks after initiation of treatment, suggestive of early progression in neuropathology. Our results do not suggest a role for glutamate as a driving factor. This study underscores the need to further research the mechanism(s) underlying this phenomenon as it has implications for early intervention to preserve cognitive decline in FEP participants.

Antipsychotic (AP) medications are the primary treatment for severe mental illnesses, including schizophrenia and severe mood disorders. APs are currently categorized into typical or first-generation APs and atypical or second-generation APs. Although both first-generation and second-generation APs are considered effective in treating psychotic symptoms in severe mental disorders, they differ in their mechanisms, treatment strategies, and side effect profiles. Because of their potential motor and metabolic side effects, which often compromise patient adherence and clinical outcomes, whether and how to use APs remains controversial. The use of dietary interventions in combination with APs is emerging as a viable strategy to reduce AP adverse effects while maintaining their efficacy and enhance patient adherence to treatment. In contrast to drugs that possess a well defined molecular mechanism of action, dietary interventions act in pleiotropic ways by nature. While providing a holistic approach to patient care this pleiotropy needs to be analyzed and systematized to enhance the efficacy and safety of the combination of them with APs. Guidelines for this type of treatment are still needed. In this review, we explore the pharmacological properties, therapeutic applications, and limitations of APs, and discuss the potential benefits and limitations of those dietary interventions that are employed to improve the efficacy and counteract side effects of APs discussing also their mechanisms of action. Finally, we critically discuss the main results of clinical studies combining APs and dietary interventions and provide a view on future directions in terms of research and clinical use of these combinations. SIGNIFICANCE STATEMENT: Antipsychotic drugs are useful in a variety of psychiatric conditions, yet their use is hampered by issues of efficacy and safety. An important step toward therapy optimization is their use in combination with dietary interventions (ie, dietary supplements and nutraceuticals) that have shown promising results in clinical trials.

Reality monitoring allows the evaluation and monitoring of reality through the assignment of information to internal or external sources, which is crucial to differentiate real events from imaginary ones. In schizophrenics, monitoring seems to be related to an error in the allocation processes, giving rise to false perceptions such as visual hallucinations, which are associated with a poor prognosis. This error can appear almost imperceptibly at an early age in life, making carrying out predictive or evaluation tests with paper and pencil unattractive. The computerization of technical resources that allow the monitoring of reality offers a new tool to evaluate the attribution process, in an effective and agile way and with easy understanding of cognitive deficits in a friendly environment.

Computerize the Memory Monitoring and Recognition Test (MMRT) evaluate reality monitoring through verbal memory tasks, improving its implementation, optimizing interaction with the user and perfecting the recording of memory errors that could indicate psychotic symptoms.

The MMRT was developed using Python and Kivy, facilitating the creation of cross-platform user interfaces. The test is structured in stages, allows voice accessibility for people with visual disabilities and provides comprehensive user management. The test data is stored in the cloud using MongoDB as the database system. Additionally, the software incorporates speech recognition using the gTTS library and generates a performance report in PDF format, documenting external, internal and global attribution errors.

The computerized version of the MMRT allowed the detection of specific errors in memory monitoring, as well as the performance of repeated measurements to evaluate long-term memory and working memory.

Preliminary applications suggest its usefulness in identifying early cognitive markers of schizophrenia, facilitating the measurement of reality monitoring through attribution errors. Developed with open-source technology and an interface adaptable to various platforms, the MMRT represents an accessible and efficient tool for psychological evaluation, with innovative potential in the study of reality monitoring.

Fractional amplitude of low-frequency fluctuation (fALFF) is a validated measure of resting-state spontaneous brain activity. Previous fALFF findings in autism and schizophrenia spectrum disorders (SSDs) have been highly heterogeneous. We aimed to use fALFF in a large sample of typically developing control (TDC), autistic, and SSD participants to explore group differences and relationships with inter-individual variability of fALFF maps and social cognition.

FALFF from 495 participants (185 TDC, 68 autism, and 242 SSD) was computed using functional magnetic resonance imaging as signal power within two frequency bands (i.e., slow-4 and slow-5), normalized by the power in the remaining frequency spectrum. Permutation analysis of linear models was employed to investigate the relationship of fALFF with diagnostic groups, higher-level social cognition, and lower-level social cognition. Each participant's average distance of fALFF map to all others was defined as a variability score, with higher scores indicating less typical maps.

Lower fALFF in the visual and higher fALFF in the frontal regions were found in both SSD and autistic participants compared with TDCs. Limited differences were observed between autistic and SSD participants in the cuneus regions only. Associations between slow-4 fALFF and higher-level social cognitive scores across the whole sample were observed in the lateral occipitotemporal and temporoparietal junction. Individual variability within the autism and SSD groups was also significantly higher compared with TDC.

Similar patterns of fALFF and individual variability in autism and SSD suggest some common neurobiological features across these related heterogeneous conditions.

Schizophrenia is characterized by language-related symptoms stemming from semantic memory disorganization, which often leads to poor social functioning. Although numerous studies have attempted to elucidate the association between these symptoms and social functioning, it remains unclear how individual differences in the degree of semantic memory disorganization are linked to variations in social functioning scores. Here, we investigated this association by utilizing advanced automated scoring techniques to quantify individual-specific semantic memory parameters from the category fluency test (CFT). Specifically, the similarity between consecutive responses from the CFT was calculated using distributional representations, forming the basis for the semantic memory organization parameters. Results showed that schizophrenia patients (n = 139) exhibited semantic memory disorganization compared to healthy controls (n = 98). Generalized linear models analyzing social functioning within the schizophrenia group, as measured by the Specific Levels of Functioning Scale, revealed that higher semantic memory parameters were associated with better social functioning scores (β = 0.07, z = 4.90, p < 0.01). These findings suggest that social functioning is related to semantic memory organization, thus providing a framework for the exploration of social functioning by assessing semantic memory organization in patients with schizophrenia.

Many people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to switch to a different antipsychotic drug.

To examine the effects of switching antipsychotic drugs in treating people with schizophrenia who have not responded to initial antipsychotic treatment.

We searched the Cochrane Schizophrenia Group Trials Register (to December 2022). We inspected the references of all included studies for further relevant trials.

We included all relevant randomised controlled trials (RCTs) comparing switching to a different antipsychotic drug rather than continuing treatment with the same antipsychotic drug for people with schizophrenia who did not respond to their initial antipsychotic treatment.

At least two review authors independently extracted data. The primary outcomes were: clinically relevant response as defined by study authors; tolerability (participants leaving the study early due to adverse effects); and quality of life assessed by the change score in the 36-Item Short Form survey. We analysed dichotomous data using the risk ratio (RR) and its 95% confidence interval (CI). We analysed continuous data using mean differences (MD) and corresponding 95% CI. We assessed the risk of bias of the included studies and used GRADE to evaluate the certainty of evidence for the following outcomes: clinically relevant response, tolerability (leaving the study early due to adverse effects), quality of life score change, acceptability (leaving the study early for any reason), general mental state (average change in general mental state scores), duration of hospitalisation, and number of participants experiencing at least one adverse effect.

We included 10 RCTs with 997 participants in the review. Nine studies used a parallel design, and one used a cross-over design. Seven studies were double-blind, two were single-blind and one did not provide any detail regarding blinding. All studies included people who were non-responsive to ongoing antipsychotic treatment. The minimum duration of the ongoing antipsychotic treatment ranged from three days to two years. The length of the comparison phase varied from two weeks to six months. The studies were published between 1993 and 2022. In about half of the studies, the methods of randomisation, allocation and blinding were poorly reported. The evidence is very uncertain regarding the effect of switching antipsychotics on clinically relevant response (RR 1.25, 95% CI 0.77 to 2.03; I² = 43%; 7 studies, 693 participants), quality of life (MD -1.30, 95% CI -3.44 to 0.84; 1 study, 188 participants), Positive and Negative Syndrome Scale (PANSS) score change (MD -0.92, 95% CI -4.69 to 2.86; I² = 47%; 6 studies, 777 participants), duration of hospitalisation (in days) (MD 9.19, 95% CI -8.93 to 27.31; I² = 0%; 2 studies, 34 participants) and the number of people experiencing at least one adverse effect (RR 1.29, 95% CI 0.81 to 2.05; I² = 36%; 3 studies, 412 participants). Compared to continuing current treatment, switching antipsychotics may result in little to no difference in tolerability, defined as the number of participants leaving the study early due to adverse effects (RR 0.73, 95% CI 0.24 to 2.26; I² = 31%; 6 studies, 672 participants; low-certainty evidence) and leaving the study early for any reason (RR 0.91, 95% CI 0.71 to 1.17; I² = 0%; 6 studies, 672 participants; low-certainty evidence).

This review synthesises currently available RCT evidence on switching antipsychotics versus continuing the same antipsychotic in individuals with schizophrenia who did not respond to their initial treatment. Overall, the evidence remains highly uncertain regarding the effects of either strategy on efficacy and safety outcomes, and no definitive recommendations can currently be made. There is an urgent need for larger, well-designed trials to identify the optimal treatment strategy for these cases.

Use of antipsychotic medication is related to thinning of the cerebral cortex, but the underlying mechanisms of this effect remain largely unknown. Here, we investigated potential mechanisms across multiple levels of description by comparing antipsychotic medication related cortical thinning to atlases of normative neurotransmitter distributions, structural and functional organization of the brain, and meta-analyses of functional activation from the Neurosynth database. We first analyzed a single-site discovery sample of patients (N = 131) with early psychosis for whom antipsychotic related cortical thinning was estimated based on lifetime exposure to antipsychotics. Findings were replicated using data from a large (N ≥ 2168) ENIGMA meta-analysis on schizophrenia patients. We discovered that antipsychotic related cortical thinning is associated with a number of neurotransmitter systems, most notably the serotonin system, as well as physiological measures, functional networks and neural oscillatory power distributions typical for regions subserving higher cognition. At the functional level, antipsychotic related cortical thinning affects regions involved in executive function and motivation, but not perception. These results show how molecular, physiological, and large-scale functional patterns may underlie antipsychotic related cortical thinning.

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and to define ascertainment criteria and primary and secondary endpoints. In addition to developing the assessment protocol, the goals of this aspect of the AMP SCZ project were: (1) to implement and monitor clinical training, ascertainment of participants, and clinical assessments; (2) to provide expert clinical input to the Psychosis Risk Evaluation, Data Integration and Computational Technologies: Data Processing, Analysis, and Coordination Center (PREDICT-DPACC) for data collection, quality control, and preparation of data for the analysis of the clinical measures; and (3) to provide ongoing support to the collection, analysis, and reporting of clinical data. This paper describes the (1) protocol clinical endpoints and outcomes, (2) rationale for the selection of the clinical measures, (3) extensive training of clinical staff, (4) preparation of clinical measures for a multisite study which includes several sites where English is not the native language; and (5) the assessment of measure stability over time in the AMP SCZ observational study comparing clinical ratings at baseline and at the 2-month follow up. Watch Dr. Jean Addington discuss her work and this article: https://vimeo.com/1040425281 .

Schizophrenia patients with auditory verbal hallucinations (AVH) frequently exhibit brain structural alterations, particularly reductions in gray matter volume (GMV).Understanding the neurobiological mechanisms underlying the changes is essential for advancing treatment strategies. To address this, a meta-analysis was conducted to identify GMV changes in schizophrenia patients with AVH and their associations with gene expression and neurotransmitter receptor profiles. The results indicated significant GMV reductions in the left and the right insula, as well as the left anterior cingulate cortex. Ontology analysis of genes associated with GMV alternations revealed enrichment in biological processes related to ion transport and synaptic transmission. Hub genes from the KCN, SCN, GN, and PRK families, along with neurotransmitter receptors such as D2, VAChT, and mGluR5, showed significant correlations with GMV changes. Furthermore, multivariate linear regression analysis demonstrated that GNB2, GNB4, PRKCG, D2, and mGluR5 significantly predicted GMV alternations. These findings suggest that GMV reductions in schizophrenia with AVH are linked to disruptions in neurobiological processes involving specific genes and neurotransmitter systems, highlighting the potential targets for therapeutic intervention.

Capacity is a dynamic, task-specific, time-specific clinical construct that may be impaired either temporarily or permanently due to the medical or psychiatric illness, necessitating varying degrees of support from caregivers. There is paucity of Indian prospective studies focusing on the mental capacity, insight, and severity of illness (SOI) in psychiatric in-patients.

The current study aimed to prospectively examine the capacity, insight, and SOI in psychiatric in-patients in a tertiary level psychiatric center.

A prospective observational study design was used to assess patient's capacity for making mental healthcare and treatment decisions, insight and SOI using the guidance document, clinical grading of insight and brief psychiatric rating scale (BPRS), respectively. In-patients aged 18 years and above, any gender and any psychiatric diagnosis as per ICD-11 diagnostic criteria were included, and intellectual developmental disorder was excluded. All assessments were conducted at the time of admission (baseline) and repeated every week until discharge.

Of 233 in-patients studied, 75% (n = 175) had incapacity and 80% (n = 187) had absent insight at the baseline. Incapacity at baseline was noted in those with delirium, catatonia, BPRS >31 (88%), absent insight (92.6%), and psychotic symptoms (94%). Only 6.42% (n = 12) of cases with the absent insight at baseline had preserved capacity. On repeated measures analysis, those with substance use disorders (SUDs; ≤1 week) and mood disorders regained capacity earlier (1-3 weeks) than psychotic disorders (>3 weeks; P < 0.001).

Insight appears to be the best discriminator for capacity status for psychotic disorders, bipolar disorders, and SUDs. Presence of delirium, catatonia, and intoxication reflect obvious lack of capacity; while absent insight, BPRS >31, psychotic and bipolar disorders suggest significant association with incapacity. Effective treatment improves capacity and insight earlier in persons with SUDs and bipolar disorders than psychotic disorders.

Stigma is prevalent among patients with schizophrenia, and its impact can be profound. Improving insight is a critical aspect of treating schizophrenia, but it is often accompanied by increased stigma. This study aims to explore how trait mindfulness and perceived social support moderate the relationship between insight and stigma in patients with stable schizophrenia. A cross-sectional study was conducted in Shanghai's Changning and Huangpu Districts from August to December 2023, recruiting patients through convenience sampling from local mental health centers. A total of 350 patients were included in the study, with their demographic information, insight, trait mindfulness, perceived social support, and stigma being measured. The study found that patients with higher BMI, unemployment or retirement status, and lower income levels experienced significantly higher stigma. The correlation analysis revealed that insight was positively correlated with stigma, while trait mindfulness and perceived social support were negatively correlated with stigma. Regression analysis showed that insight increased stigma, whereas trait mindfulness and perceived social support reduced it. Moderation analysis indicated that higher levels of both trait mindfulness and perceived social support significantly reduced the negative impact of increased insight on stigma in patients with schizophrenia. These findings highlight the importance of enhancing patients' trait mindfulness and perceived social support while improving insight in the treatment of schizophrenia.

The Positive and Negative Syndrome Scale (PANSS) is the most widely used tool for assessing the symptoms of schizophrenia. Despite its widespread use, the psychometric properties of the PANSS have not been systematically reviewed. This study fills that gap in the scientific literature.

We utilized the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews and meta-analytical procedures to assess the psychometric properties of the PANSS in its original three-subscale form as well as the quality level of the evidence available. On this basis we formulated recommendations for future research and use. A study protocol was registered under 10.17605/OSF.IO/5EGMD. The search period was until February 21, 2024.

We included 119 publications. According to COSMIN, the PANSS demonstrated sufficient reliability, construct validity, and responsiveness; but had significant shortcomings in content validity and structural validity. The original three-factor model showed poor structural validity, leading to its COSMIN classification as "not recommendable". The subscales showed overall acceptable measurement properties. However, the lack of structural validity of the three-subscale model renders its subscales less useful. Moreover, the PANSS negative subscale does not cover all domains of the National Institute of Mental Health consensus. Due to the length of the instrument (30-50 min), it is barely useable in clinical practice.

Although the PANSS is the standard scale for schizophrenia symptom severity, its shortcomings regarding fundamental psychometric domains and practical applicability warrant the development of new scales for which appropriate methods should be applied from the start.

There was no specific funding source for this research.

The field of Clinical High-Risk for Psychosis (CHR-P) is a dynamic area within contemporary psychiatry and serves as a crucial testing ground for precision prognostic models. Nonetheless, some foundational aspects remain inadequately conceptualized and consequently not transparently reported, such as baseline pharmacotherapy. A systematic review and meta-analysis were conducted by searching the MEDLINE and Cochrane Library databases for studies published up to August 31, 2024. Eligible studies included CHR-P samples, reported numeric data on outcomes at follow-up, and examined the transition to psychosis as an outcome. Data extraction adhered to PRISMA guidelines, focusing on baseline pharmacological exposure to antipsychotics, antidepressants, benzodiazepines, and mood stabilizers. A total of 95 studies were analyzed. The majority of studies (96.8 %) explicitly stated whether baseline exposure to antipsychotics was allowed as part of the inclusion criteria. However, actual baseline exposure to antipsychotics was quantified in only 60 % of these studies. Exposure to non-antipsychotic psychoactive therapies was reported in only a fraction of the studies (36.8 % for antidepressants, 16.8 % for benzodiazepines, and 14.7 % for mood stabilizers). In CHR-P longitudinal studies, the meta-analytic proportions of self-disclosed baseline pharmacological exposure ranged from 23.5 % to 24.5 % for antipsychotics, 28.5 % to 30.6 % for antidepressants, 11.2 % to 14.6 % for benzodiazepines, and 5.6 % to 5.9 % for mood stabilizers. Overall, a non negligible fraction of CHR-P participants is already under psychoactive pharmacological treatment at enrollment. The lack of consistent transparency in this respect may limit the effectiveness of prognostic models. Improved reporting practices are necessary to enhance precision in preventive psychiatry.