Medication-induced dystonia (MID) is a movement disorder (MD), characterized by involuntary sustained or intermittent muscle contractions, causing abnormal, often repetitive, movements, postures, or both. Although MID is commonly associated with the use of antipsychotics, it also occurs with many other medications widely used in clinical practice.

A systematic literature search (from inception to November 2023), using the PubMed and Embase databases, was conducted without language restriction for articles reporting on MID in people without pre-existing MDs, and this for all potentially relevant non-antipsychotic medications. A narrative synthesis of the available evidence was undertaken.

MID is common (1 to 10%) with certain antiemetics. Selective serotonin reuptake inhibitors and the antiepileptics valproate, carbamazepine, and lamotrigine are rarely (0.01 to 0.1%) or very rarely (<0.01%) associated with MID. All other medications are very rarely (<0.01%) associated with MID or have a risk that cannot be precisely estimated. The actual rate of dystonic reactions with most non-antipsychotic agents remains unknown, owing to misdiagnosis and underreporting in the scientific literature. In general, MID seems to occur more often in children and adolescents, even with a single low dose, and with polymedication. In most cases, MID is acute in onset (occurring within hours to days) and involves the head and neck.

Although MID is most common with dopamine receptor-blocking antiemetics, many other medications may also produce dystonic reactions, particularly in children and adolescents. Although such incidents remain rare, there are indications that MID is underreported for many classes of medications.

The development of guidelines is time-consuming and cost-intensive. The heterogeneity of clinical practice, evidence, and patients’ needs is an issue across Europe. An European core guidance for a specific psychiatric disorder may help to overcome this issue. Here, we present a progress report on the European Psychiatric Association (EPA) proof-of-concept approach to develop a European consensus guidance on the pharmacological treatment of schizophrenia.

All national psychiatric associations in Europe were contacted to provide their schizophrenia guidelines. Six guidelines were rated by three experts, experienced in the development of national and international guidelines, from three different countries (Italy, Hungary, and Germany), and the German schizophrenia guideline published in 2019 was found to have the highest quality. For this proof-of-concept approach, 45 recommendations on the pharmacological treatment of schizophrenia from the German guideline were evaluated in a two-step Delphi process to determine their acceptability throughout the European continent.

44 experts participated in the first round and 40 experts in the second round of the Delphi process. Agreement among the involved experts was reached for 75% of the presented recommendations from the German schizophrenia guidelines. 11 out of 45 recommendations (24.4%) did not reach this level of agreement.

This progress report highlights the possibility of developing a pan-European core guidance on the pharmacological treatment of schizophrenia by adapting national guidelines and reconciling their recommendations. However, several barriers in this adaptation process, such as non-agreement in recommendations with strong scientific evidence in the reconciling process, were identified and must be considered when developing the final guidance.

Beyond psychosis prediction, clinical high-risk (CHR-P) symptoms show clinical relevance by their association with functional impairments and psychopathology, including personality pathology. Impaired personality functioning is prioritized in recent dimensional personality disorder models (DSM-5, ICD-11), yet underexplored in CHR-P, as are associations with cognitive biases, which early studies indicate as possibly linking CHR-P-symptoms and personality pathology.

A community sample (N = 444, 17–60 years, 61.8% female) was assessed via clinical telephone interview and online questionnaires. Using zero-inflated Poisson models, we explored associations of personality functioning, cognitive biases, current psychopathology, and psychosocial functioning with likelihood and severity of overall CHR-P, as well as perceptive (per-) and non-perceptive (nonper-)CHR-P-symptoms distinctly.

Higher nonper-CHR-P-symptom likelihood was associated with more impaired personality functioning and psychosocial functioning, while more severe cognitive biases were associated with higher CHR-P- and per-CHR-P-symptom likelihood, alongside higher CHR-P- and nonper-CHR-P-symptom severity. Further, more axis-I diagnoses were linked to higher CHR-P-, per-CHR-P-, and nonper-CHR-P-symptom likelihood, and younger age to higher CHR-P- and per-CHR-P-symptom severity, with CHR-P-symptom severity appearing higher in females. In an exploratory analysis, personality functioning elements identity and self-direction, and cognitive biases dichotomous thinking, emotional reasoning, and catastrophizing, respectively, showed multifaceted associations with nonper-CHR-P-symptom likelihood and overall CHR-P-symptom expression.

Our study supports the association of CHR-P-symptoms with multiple mental health factors. Findings suggest intricate associations between personality functioning impairments and cognitive biases with CHR-P-symptom expression in non-help-seeking populations, possibly contributing to different per-CHR-P- and nonper-CHR-P-symptom expression patterns. Therefore, they should be targeted in future longitudinal studies, aiming at better understanding CHR-P-manifestations to inform preventive intervention.

Racial and ethnic experiences of discrimination (EODs) are associated with numerous psychiatric symptoms, including outcomes along the psychosis spectrum; however, less is known about mechanisms by which EODs confer risk for psychotic-like experiences (PLEs; common subthreshold psychotic symptoms). Furthermore, work on gendered racism asserts that the intersection of race and gender impacts the nature of EODs experienced and, in turn, may impact the relationship between EODs and PLEs.

To utilize an intersectional lens (race and gender) to examine whether psychological correlates of EODs (post-traumatic stress, anxiety, depression, and dissociation) mediate the EOD–PLE relationship.

Undergraduates at a diverse, semipublic university (N = 1,759) completed self-report questionnaires (Experiences of Discrimination Scale, Prodromal Questionnaire, Center for Epidemiologic Studies Depression Scale, State–Trait Anxiety Inventory, Dissociative Experiences Scale, and Post-Traumatic Stress Disorder Checklist – Civilian Version). Analyses stratified the sample by race (non-Hispanic White, Black, and Asian) and examined three multiple mediation models, moderated by gender, examining the pathway from EODs to PLEs, through other psychiatric symptoms.

In the full sample, all psychiatric symptoms significantly mediated the relationship between EODs and PLEs. Only depression varied by gender, such that the indirect effect was only significant in female participants (β = 0.09; 95% CI [0.02, 0.16]). Across race-stratified groups, significant mediators varied by both race and gender.

These findings underscore the importance of accounting for intersectionality and multiple psychological symptoms in understanding the EOD–PLE associations, which differ by race and ethnicity as well as gender, and should be considered in clinical treatment of individuals with PLEs and history of EODs.

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.

Cognitive impairment is a core feature of psychosis, which adversely affects global functioning and quality of life and has been consistently reported from the early stages of illness. Patients with first-episode psychosis (FEP) exhibit deficits in processing speed, short-term memory, attention, working memory, and executive functioning, which respond poorly to psychotropic drugs. Among non-pharmacological approaches, physical activity has shown promise in improving cognitive functioning in schizophrenia spectrum disorders. However, current evidence lacks specific data on individuals with FEP. In this review, we aim to explore the potential role of physical activity-based interventions in ameliorating the cognitive functions of people with FEP.

The literature search was conducted on PubMed, PsycINFO, and Web of Science in March 2024, identifying 127 de-duplicated records. One additional article was identified by screening the reference lists of the included studies. A total of six studies fulfilled the inclusion criteria and were reviewed. They all analyzed the effect of structured physical activity interventions on the cognitive functioning of patients with FEP.

Preliminary findings suggest that physical activity interventions enhance memory, attention, and executive functions of patients with FEP but not social cognition and motor function.

Study differences in sample characteristics, design, and intervention protocols prevent firm conclusions about the cognitive-boosting effects of the interventions in FEP. Further studies using more rigorous methodologies are needed to understand the durability of these effects and the underlying mechanisms.

While several risk factors for schizophrenia have been identified, their individual impacts are rather small. The relative independent and cumulative impacts of multiple risk factors on disease risk and age of onset warrant further investigation.

We conducted a register-based case–control study including all individuals receiving a schizophrenia spectrum disorder in Denmark from 1973 to 2018 (N = 29,142), and a healthy control sample matched 5:1 on age, sex, and parental socioeconomic status (N = 136,387). Register data included parental history of psychiatric illness, birth weight, gestational age, season of birth, population density of birthplace, immigration, paternal age, and Apgar scores. Data were analysed using logistic regression and machine learning.

Parental history of psychiatric illness (OR = 2.32 [95%CI 2.21–2.43]), high paternal age (OR = 1.30 [1.16–1.45]), and low birth weight (OR = 1.28 [1.16–1.41]) increased the odds of belonging to the patient group. In contrast, being a second-generation immigrant (OR = 0.65 [0.61–0.69]) and high population density of the birthplace (OR = 0.92 [0.89–0.96]) decreased the odds. The findings were supported by a decision tree analysis where parental history, paternal age, and birth weight contributed most to diagnostic classification (ACCtest = 0.69, AUCtest = 0.59, p < 0.001). Twenty percent of patients were child-onset cases. Here, female sex (OR = 1.82 [1.69–1.97]) and parental psychiatric illness (OR = 1.62 [1.49–1.77]) increased the odds of receiving the diagnosis <18 years.

Multiple early factors contribute independently to a higher psychosis risk, suggesting cumulative effects leading to symptom onset. Routine assessments of the most influential risk factors could be incorporated into clinical practise. Being female increased the risk of diagnosis during childhood, suggesting sex differences in the developmental trajectories of the disorder.

We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia.

We recruited 92 participants with first-episode psychosis (FEP, n = 92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors.

Most people started treatment with risperidone (n = 57), followed by olanzapine (n = 29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications.

Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

High rates of psychiatric comorbidities have been found in people with problem gambling (PBG), including substance use, anxiety, and mood disorders. Psychotic disorders have received less attention, although this comorbidity is expected to have a significant impact on the course, consequences, and treatment of PBG. This review aimed to estimate the prevalence of psychotic disorders in PBG.

Medline (Ovid), EMBASE, PsycINFO (Ovid), CINAHL, CENTRAL, Web of Science, and ProQuest were searched on November 1, 2023, without language restrictions. Studies involving people with PBG and reporting the prevalence of schizophrenia spectrum and other psychotic disorders were included. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist for systematic reviews of prevalence data. The pooled prevalence of psychotic disorders was calculated using a random effects generalized linear mixed model and presented with forest plots.

Of 1,271 records screened, 22 studies (n = 19,131) were included. The overall prevalence of psychotic disorders was 4.9% (95% CI, 3.6–6.5%, I2 = 88%). A lower prevalence was found in surveyed/recruited populations, compared with treatment-seeking individuals and register-based studies. No differences were found for factors such as treatment setting (inpatient/outpatient), diagnoses of psychotic disorders (schizophrenia only/other psychotic disorders), and assessment time frame (current/lifetime). The majority of included studies had a moderate risk of bias.

These findings highlight the relevance of screening problem gamblers for schizophrenia spectrum and other psychotic disorders, as well as any other comorbid mental health conditions, given the significant impact such comorbidities can have on the recovery process.

Predominant negative symptoms (PNSs) in schizophrenia can affect the patients’ psychosocial functioning immensely and are less responsive to treatment than positive symptoms.

The aim of the study was to observe negative symptoms and psychosocial functioning in PNS schizophrenia patients and to understand whether PNS can be improved and with what treatment strategies.

This was a 1-year, prospective, multicentric cohort study conducted in Slovakia. Adult outpatients with diagnosis of schizophrenia according to ICD-10 and PNS evaluated using the criteria by the European Psychiatric Association’s (EPA) guidance were included. Change in negative symptoms, functionality, and treatment patterns were observed. Treatment effectiveness was evaluated using the modified Short Assessment of Negative Domain (m-SAND), the Self-evaluation of Negative Symptoms (SNS) scale, the Personal and Social Performance (PSP) scale, and the Clinical Global Impression – Severity (CGI-S) and the Clinical Global Impression – Improvement (CGI-I) scales. Least-squares (LS) means were calculated for the change from baseline to final visit for the outcomes.

The study included 188 patients. Functionality improved as, by the end of the study, fewer patients were unemployed (53%) and more worked occasionally (21%). PNS improved significantly according to both physicians and patients (LS mean change from baseline in m-SAND total score: -10.0 (p-value <0.0001)). Most patients received polytherapy throughout the study. Cariprazine was utilized most (20% monotherapy and 76% polytherapy). Only a few patients discontinued treatment due to adverse drug reactions.

With the right treatment strategy, it is possible to achieve improvement in PNS and everyday functioning in schizophrenia outpatients.

Although obsessive–compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients’ real-life functioning is still controversial.

The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables.

A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild–moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive–compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive–compulsive symptoms (OCS) were not associated with functioning, whereas in the mild–moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild–moderate OCS and more preserved levels of functioning.

These findings hint at a positive association between mild–moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.

One of the challenges of psychiatry is the staging of patients, especially those with severe mental disorders. Therefore, we aim to develop an empirical staging model for schizophrenia.

Data were obtained from 212 stable outpatients with schizophrenia: demographic, clinical, psychometric (PANSS, CAINS, CDSS, OSQ, CGI-S, PSP, MATRICS), inflammatory peripheral blood markers (C-reactive protein, interleukins-1RA and 6, and platelet/lymphocyte [PLR], neutrophil/lymphocyte [NLR], and monocyte/lymphocyte [MLR] ratios). We used machine learning techniques to develop the model (genetic algorithms, support vector machines) and applied a fitness function to measure the model’s accuracy (% agreement between patient classification of our model and the CGI-S).

Our model includes 12 variables from 5 dimensions: 1) psychopathology: positive, negative, depressive, general psychopathology symptoms; 2) clinical features: number of hospitalizations; 3) cognition: processing speed, visual learning, social cognition; 4) biomarkers: PLR, NLR, MLR; and 5) functioning: PSP total score. Accuracy was 62% (SD = 5.3), and sensitivity values were appropriate for mild, moderate, and marked severity (from 0.62106 to 0.6728).

We present a multidimensional, accessible, and easy-to-apply model that goes beyond simply categorizing patients according to CGI-S score. It provides clinicians with a multifaceted patient profile that facilitates the design of personalized intervention plans.

The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question.

To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample.

The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components.

FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ.

PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients’ lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

Paliperidone palmitate 3-monthly (PP3M) has been tested in 1-year controlled studies. The aim of this study was to examine the relapse outcomes with PP3M monotherapy at 3 years in patients with schizophrenia.

This was an observational, non-interventional study of patients started on PP3M according to their clinical need. All patients had a diagnosis of schizophrenia (ICD-10 F20) and were between 18 and 65 years of age. The study took place in a mental health facility in South East London, UK.

Among the 166 patients who started PP3M, 97 (58%) met inclusion criteria and were observed for 36 months. In total, five patients (5%) experienced a relapse (defined as step-up in clinical care) while on PP3M. There were no relapses between months 18 and 36. Of the original 97 patients, 56 (58%) remained on PP3M monotherapy at 3 years, and 71 (73%) remained on either PP3M or paliperidone palmitate one-monthly. Reasons for discontinuation of PP3M included patient refusal (n = 11, 33% of discontinuations) and adverse effects in (n = 8, 24%).

PP3M is a highly effective monotherapy treatment for reducing relapse in people with schizophrenia.