Minor physical anomalies (MPAs) are anatomical variations that are markers of aberrant early neurodevelopment. Schizophrenia is associated with increased MPA frequency, however, the frequency and distribution of MPAs exhibit substantial heterogeneity in schizophrenia and are not exclusive to this disorder. MPAs at different localizations might represent different developmental origins and might be related to latent genetic predisposition or vulnerability to develop full-blown psychosis. Therefore, we conducted a thorough review of minor physical anomalies (MPAs) in schizophrenia (Sch) and first-degree relatives (SchRel). Analyzing 52 studies published from January 1980 to October 2023, the meta-analysis compared MPA scores between 3780 schizophrenia patients and 3871 controls, as well as 1415 SchRel and 1569 controls. The total MPA score was significantly increased in schizophrenia compared to controls (g = 0.78 [0.63-0.93], p<0.001). In regional MPA meta-analyses, effect sizes ranged from 0.56 to 0.78. The difference between SchRel and controls was moderate (g = 0.44 [0.28-0.61], p<0.001). When individual MPA items were analyzed separately, fine electric hair, malformed ear, asymmetrical ear, curved 5th finger were anomalies that were shared between both schizophrenia and SchRel. Also, direct comparisons of the frequency of MPAs in schizophrenia and their relatives were conducted. Additionally, the early age of onset of schizophrenia was associated with mouth anomalies (Z=-2.13, p = 0.03), and ear anomalies were associated with a higher percentage of males in the schizophrenia group (Z = 2.64, p = 0.008). These findings support the notion that different MPAs might be associated with genetic susceptibility as well as vulnerability to developing full-blown psychosis. Studies investigating clinical and neurobiological correlates of MPAs in schizophrenia might be helpful in characterizing subtypes of psychoses that are associated with different developmental processes.

OBJECTIVE: Substance use is highly prevalent among people with schizophrenia (SCZ) and related disorders, however, there is no broad-spectrum pharmacotherapy that concurrently addresses both addiction and psychotic symptoms. Psychosocial (PS) interventions, which have yielded promising results in treating psychosis and substance dependence separately, demonstrate potential but have not been systematically evaluated when combined.
METHODS: Systematic review and random-effects meta-analyses of randomized controlled trials (RCTs) investigating PS interventions for individuals with comorbid substance use and psychotic disorders, encompassing SCZ and schizophrenia spectrum disorders (SSD). We included relevant studies published from MEDLINE, PsycINFO, and Google Scholar through May 2023.
RESULTS: We included 35 RCTs (5176 participants total; approximately 2840 with SSD). Intervention durations ranged from 30 min to 3 years. Meta-analysis did not identify a statistically significant pooled PS intervention effect on the main primary outcome, substance use (18 studies; 803 intervention, 733 control participants; standardized mean difference, -0.05 standard deviation [SD]; 95% CI, -0.16, 0.07 SD; I2 = 18%). PS intervention effects on other outcomes were also not statistically significant. Overall GRADE certainty of evidence was low.
CONCLUSIONS: At present, the literature lacks sufficient evidence supporting the use of PS interventions as opposed to alternative therapeutic approaches for significantly improving substance use, symptomatology, or functioning in people with SCZ and related disorders. However, firm conclusions were precluded by low certainty of evidence. Further RCTs are needed to determine the efficacy of PS treatments for people with dual-diagnoses (DD), either alone or in combination with pharmacotherapy.

BACKGROUND: Schizophrenia is heavily stigmatized among health professionals. Given that health professional students are future members of the workforce and will provide care for people with schizophrenia, it is essential to implement interventions aimed at reducing stigma among this group.
OBJECTIVE: This scoping review aimed to identify and synthesize existing literature on interventions to decrease schizophrenia stigma among health professional students, and to determine the possible gaps in the literature.
METHODS: Nine electronic databases and gray literature were searched, including PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, MEDLINE, Web of Science, Scopus, China National Knowledge Infrastructure, WanFang, and Google on 5 May 2023. Two researchers independently conducted data screening, data extraction, and assessed study risks. A most updated search was also done on 22 May 2024. The Cochrane risk of bias tool version 2 for randomized trials and Risk of Bias in Non-randomized Studies were used to assess the studies\' risk of bias. Data synthesis and analysis were conducted by two reviewers using a narrative approach. Reporting adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.
RESULTS: This review included twenty-one studies with 2520 health professional students. The majority of included studies were non-randomized controlled trials (38 %) and pre-post studies (52 %). Most of the included studies were conducted in the United States (24 %). The participants in ten (48 %) studies were medical students. The number of intervention sessions ranged from one to 13, with an average of three. Seven (33 %) studies had an intervention duration of less than four weeks and 16 (76 %) studies had no follow-up. Various scales were used to assess the outcomes of schizophrenia stigma. Only two studies (10 %) indicated the intervention\'s ineffectiveness, with the majority of interventions led by psychiatry department faculty and individuals with schizophrenia.
CONCLUSIONS: Most studies (90 %) utilized various approaches, including face-to-face or online education, direct contact with individuals with schizophrenia, or a combination thereof, to diminish stigma among health professional students. However, none addressed cultural and empathy factors in their intervention designs, and the included studies lacked theoretical guidance. The review only comprised English quantitative studies with significant heterogeneity, with 17 studies (81 %) displaying serious or high risk of bias, limiting comprehensive discussions. These findings offer valuable insights for future systematic review. Tweetable abstract Studies on reducing health professional students\' schizophrenia stigma need to address cultural and empathy factors.

OBJECTIVE: N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be determined whether the physiological changes observed following NMDA-R antagonist administration are consistent with auditory gamma-band activity in ScZ which is dependent on NMDA-R activity.
METHODS: This systematic review investigated the effects of NMDA-R antagonists on auditory gamma-band activity in preclinical (n = 15) and human (n = 3) studies and compared these data to electro/magneto-encephalographic measurements in ScZ patients (n = 37) and 9 studies in early-stage psychosis. The following gamma-band parameters were examined: (1) evoked spectral power, (2) intertrial phase coherence (ITPC), (3) induced spectral power, and (4) baseline power.
RESULTS: Animal and human pharmacological data reported a reduction, especially for evoked gamma-band power and ITPC, as well as an increase and biphasic effects of gamma-band activity following NMDA-R antagonist administration. In addition, NMDA-R antagonists increased baseline gamma-band activity in preclinical studies. Reductions in ITPC and evoked gamma-band power were broadly compatible with findings observed in ScZ and early-stage psychosis patients where the majority of studies observed decreased gamma-band spectral power and ITPC. In regard to baseline gamma-band power, there were inconsistent findings. Finally, a publication bias was observed in studies investigating auditory gamma-band activity in ScZ patients.
CONCLUSIONS: Our systematic review indicates that NMDA-R antagonists may partially recreate reductions in gamma-band spectral power and ITPC during auditory stimulation in ScZ. These findings are discussed in the context of current theories involving alteration in E/I balance and the role of NMDA hypofunction in the pathophysiology of ScZ.

Background and Objectives: Radicalization, a complex and multifaceted phenomenon, has been a subject of increasing concern in recent years, particularly due to its potential connection to acts of mass violence and terrorism. This systematic review examines the intricate link between radicalization and psychotic disorders, utilizing various sources such as observational studies, case reports, and series. It aims to highlight the prevalence of schizophrenia spectrum and other psychotic disorders among radicalized individuals and to define the role of mental health professionals in dealing with this issue, contributing to the development of prevention and treatment strategies. Materials and Methods: The methodology involved an extensive literature search across PubMed, Scopus, and APA PsycINFO up to 1 February 2024, adhering to PRISMA guidelines. The study focused on radicalization and psychotic disorders as defined by DSM-5 criteria, excluding other mental disorders. A population sample of 41 radicalized individuals diagnosed with psychotic disorders was selected, among which schizophrenia was identified as the predominant condition. Results: It was observed that 24% of these individuals passed away soon after committing their crimes, leading the researchers to rely on retrospective data for their diagnoses. The use of diverse assessment tools for psychiatric diagnosis and the lack of a standardized method for diagnosing or assessing involvement in the radicalization process were also noted. Despite limitations like reliance on observational studies and case reports, which result in low evidence quality and varied methodologies, our work provides a valuable contribution to clarifying the relationship between radicalization and psychotic disorders. However, further clinical studies are needed to delve deeper into these aspects. Conclusions: In conclusion, our review points out that individuals with psychotic disorders do not have a higher crime rate than the general population and warns against associating crimes with mental illness due to the stigma it creates. The lack of uniform psychiatric diagnostic tools and radicalization assessment highlights the need for more standardized risk assessment tools and validated scales in psychiatric diagnosis to better understand the relationship between radicalization and psychotic disorders and to develop integrated protocols.

The sense of agency is the experience of being the author of self-generated actions and their outcomes. Both clinical manifestations and experimental evidence suggest that the agency experience and the mechanisms underlying agency attribution may be dysfunctional in schizophrenia. Yet, studies investigating the sense of agency in these patients show seemingly conflicting results: some indicated under-attribution of self-agency (coherently with certain positive symptoms), while others suggested over-attribution of self-agency. In this review, we assess whether recent theoretical frameworks can reconcile these divergent results. We examine whether the identification of agency abnormalities in schizophrenia might depend on the measure of self-agency considered (depending on the specific task requirements) and the available agency-related cues. We conclude that all these aspects are relevant to predict and characterise the type of agency misattribution that schizophrenia patients might show. We argue that one particular model, based on the predictive coding theory, can reconcile the interpretation of the multifarious phenomenology of agency manifestations in schizophrenia, paving the way for testing agency disorders in novel ways.

Among the pathophysiological correlates of schizophrenia, recent research suggests a potential role for the Hedgehog (Hh) signalling pathway, which has been traditionally studied in embryonic development and oncology. Its dysregulation may impact brain homeostasis, neuroplasticity, and potential involvement in neural processes. This systematic review provides an overview of the involvement of Hh signalling in the pathophysiology of schizophrenia and antipsychotic responses. We searched the PubMed and Scopus databases to identify peer-reviewed scientific studies focusing on Hh and schizophrenia, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, finally including eight studies, including three articles focused on patients with schizophrenia, two animal models of schizophrenia, two animal embryo studies, and one cellular differentiation study. The Hh pathway is crucial in the development of midbrain dopaminergic neurons, neuroplasticity mechanisms, regulating astrocyte phenotype and function, brain-derived neurotrophic factor expression, brain glutamatergic neural transmission, and responses to antipsychotics. Overall, results indicate an involvement of Hh in the pathophysiology of schizophrenia and antipsychotic responses, although an exiguity of studies characterises the literature. The heterogeneity between animal and human studies is another main limitation. Further research can lead to better comprehension and the development of novel personalised drug treatments and therapeutic interventions.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
CONCLUSIONS: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
BACKGROUND: PROSPERO-ID CRD42023410645.

UNASSIGNED: Negative symptoms of schizophrenia (NSS) have been linked with poor functional outcomes. A literature review was performed to identify instruments used to assess functional outcomes and quality of life in clinical trials and observational studies conducted in groups of people with NSS.
UNASSIGNED: Literature search strings were designed using Medical Subject Headings combined with free-text terms and searches were performed using the PubMed, Embase and the Cochrane Library databases. For inclusion, articles were required to be published as full-text articles, in English, over the period 2011-2021, include at least one group or treatment arm of people with NSS and report either functional outcomes or quality of life (QoL).
UNASSIGNED: Literature searches identified a total of 3,268 unique hits. After two rounds of screening, 37 publications (covering 35 individual studies) were included in the review. A total of fourteen different instruments were used to assess functional outcomes and eleven different instruments were used to assess QoL. In studies in people with NSS, the most frequently used functional outcome measures were the Personal and Social Performance scale and the Global Assessment of Functioning. The most frequently used QoL instruments included the Manchester Short Assessment of Quality of Life, the Heinrich Carpenter Quality of Life Scale, the Schizophrenia Quality of Life Scale and the EQ-5D.
UNASSIGNED: A large number of measures have been used to assess functional outcomes and QoL in people with NSS, these include both generic and condition-specific as well as both interviewer-administered and self-reported instruments.

UNASSIGNED: Schizophrenia is most times a chronic and often debilitating illness associated with poor mental health outcomes. Early and effective treatment of schizophrenia in the most appropriate setting can make a significant difference in the long-term recovery. The aim of this narrative review was to provide suggestions and recommendations for effectively managing patients with schizophrenia during acute exacerbations and to enhance awareness and skills related to personalized medicine.
UNASSIGNED: A panel of academics and clinicians with experience in the field of psychosis met virtually on July 13th 2023 to narratively review and discuss the research evidence and their clinical experience about the most appropriate acute treatments for patients with schizophrenia. This manuscript represents a synthesis of the panel analysis and discussion.
UNASSIGNED: First contact is very important for service users, as is finding the most adequate treatment setting. If patients present to the emergency department, which may be a traumatic setting for service users, a dedicated environment with adequate space and specialized mental health support, including personnel trained in de-escalation techniques, is recommended. A well-connected continuum of care is strongly recommended, possibly with seamless links between inpatient units, day hospital services, outpatient facilities and rehabilitation services. Ideally, this should be structured as part of a coordinated step-down service line. Treatment challenges include suboptimal response, side effects, and nonadherence, which is reduced by the use of long-acting injectable antipsychotics.
UNASSIGNED: Individual circumstances, including age, gender, and presence of hostility/aggression or self-harm, cognitive impairment and negative symptoms, comorbidities (depression, substance use disorders) or associated symptoms (anxiety, insomnia), should be considered when selecting the most appropriate treatment for the acute phase of schizophrenia. Efficacy and feasibility, as well as acceptability and tolerability of treatments, require joint consideration from the early stages of schizophrenia, thereby enhancing the possibility of improved short- and long-term outcomes.