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Background: The concept of recovery for people with schizophrenia (PwS) is still a matter of debate. Growing numbers of PwS living to older age calls for examination of their disease trajectories with a focus on recovery. Aim: To compare two groups of PwS (good wellbeing; poor wellbeing) on several psychosocial variables associated with social wellbeing to identify interventions that support functional recovery. Method: Data was drawn from participants from across New Zealand (NZ), who had received a formal diagnosis of Schizophrenia; were living independently in the community, and who had undergone their first International Resident Assessment Instrument (interRAI) assessment from 2012 to 2022. We compared two groups of PwS (good social wellbeing; poor social wellbeing) examining associations with demographic and psychosocial variables. Results: We compared interRAI assessments for: 'poor psychosocial wellbeing' (n = 1,378; 67%; 56% female; 70.5% 65 years and over; 36.1% never married); and 'good psychosocial wellbeing' (n = 693; 33%; 61.1% female; 78.1% 65 years and over; 29.8% never married; n = 549 did not have sufficient social wellbeing data to be included). We found significant associations between social wellbeing and depression, disruptive behaviour, decision making, self-expression, understanding verbal information, activity level, self-reported health and medication adherence. Logistical regression showed depression (β =.84, p <.001, Wald = 51.01, Exp(B) = 2.31) and mild disruptive behaviour (β =.63, p =.002, Wald = 9.26, Exp(B) = 0.53) were the only predictors of poor social wellbeing. Those who reported some degree of depressive symptoms were 2.31 (CI [1.84, 2.91]) more likely to be in the poor social wellbeing group. Conclusions: A significant minority (33.5%) of older PwS enjoy positive social wellbeing. Several psychosocial variables are associated with wellbeing. By addressing the comorbidity of depressive symptoms, we may be able to improve wellbeing for older PwS. [ABSTRACT FROM AUTHOR]

Background: Severe mental illnesses (SMIs), including schizophrenia and bipolar disorder affect patients significantly. Gender has been identified as a key factor influencing the experience of SMIs with notable disparities in prevalence, symptoms, and treatment outcomes. Additionally, the quality of life (QoL) and social support for patients with SMIs can vary based on gender. Aims: This study examined gender differences in QoL and social support of patients with SMIs. Method: Participants include 170 outpatients with schizophrenia and bipolar disorder at Shafa Hospital (2021). QoL and social support were assessed using World Health Organization QoL (WHOQOL-BREF) questionnaire and Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Group differences were analyzed using t -test or Mann–Whitney U test, and two-way multivariate analyses of variance explored the effect of gender and disease type. Results: It was indicated that females with schizophrenia reported higher QoL than males, but the opposite was observed for bipolar disorder. Gender differences in social support were not significant among schizophrenia patients, nor between the two patient groups. However, women with bipolar disorder and multiple hospitalizations experienced lower social support and QoL compared to men. Additionally, more hospitalizations were associated with decreased QoL in both genders with schizophrenia. Conclusions: Findings suggest the need for gender- specific interventions and support policies to enhance QoL and social support in patients with SMI. [ABSTRACT FROM AUTHOR]

Background: Among the multiple challenges that people experiencing mental illness in general, and schizophrenia or bipolar disorders in particular, have to face, stigma appears to be one of the most difficult to tackle. In France, the body of research about stigma regarding people experiencing schizophrenia or bipolar disorders is growing, but not as much as in other western countries. Aims: In this context, our study aims to explore and compare stigma in French people experiencing schizophrenia or bipolar disorders, along with their respective mental healthcare system experience, in order to better address them within public health policies. Methods: 20 French mental health service users experiencing schizophrenia and 20 experiencing bipolar disorders answered the Stigma Scale, which assesses three dimensions of stigma (discrimination, difficulties of divulgation and lack of positive aspects). A semi-structured interview was used to collect information about the experience of the mental healthcare system (level of information, access to diagnosis, treatment, access to psychoeducation, etc.). Results: People experiencing schizophrenia and people experiencing bipolar disorders are different populations in terms of social impairment. However, they share a comparable negative experience of the mental healthcare system and a comparable level of information about their illness, to the exception of diagnosis divulgation, as people experiencing bipolar disorders have a better access to their diagnosis. People experiencing schizophrenia perceive a higher actual discrimination than people experiencing bipolar disorders. Conclusions: Public health policies should take into account the strong perception of actual discrimination of people experiencing schizophrenia, with capitalizing on what seems beneficial for people experiencing bipolar disorders. [ABSTRACT FROM AUTHOR]

Aim: Oral function in patients with schizophrenia has not been well‐characterized. To address this, we performed a cross‐sectional study of oral function in Japanese inpatients with schizophrenia. Methods: We measured oral function, including occlusal force, tongue–lip motor function, tongue pressure, and masticatory function in 130 Japanese inpatients with schizophrenia. We then compared the frequency of clinical signs of oral hypofunction among 63 non‐elderly and 67 elderly inpatients with schizophrenia, as well as data from 98 elderly control participants from a previous Japanese study. Results: The frequency of reduced occlusal force was significantly higher in the elderly inpatients (76.2%) than in the non‐elderly inpatients (43.9%) and elderly controls (43.9%). The frequency of decreased tongue–lip motor function in non‐elderly inpatients (96.8%) and elderly inpatients (97.0%) was significantly higher than that in elderly controls (56.1%). The frequency of decreased tongue pressure in non‐elderly inpatients (66.1%) and elderly inpatients (80.7%) was significantly higher than that in elderly controls (43.9%). Finally, the frequency of decreased masticatory function was highest in elderly inpatients (76.5%), followed by non‐elderly inpatients (54.8%) and elderly controls (15.3%). Conclusion: Oral function was decreased in both non‐elderly and elderly Japanese inpatients with schizophrenia compared with elderly controls. [ABSTRACT FROM AUTHOR]

Multiplex immunoassays have been developed to detect multiple proteins simultaneously and are used to search for biomarkers, including those present in major psychiatric disorders. This study aimed to review multiplex immunoassay studies on cerebrospinal fluid (CSF) biomarkers in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) and examine future research directions using improved proteomic techniques. According to the results of previous multiplex immunoassay studies, increased CSF IFN‐β, IL‐8, MCP‐2, MMP‐2, PAI‐1, sICAM‐1, and sVCAM‐1 and decreased CSF ACE, APP, fibrinogen, and GDNF were observed in patients with schizophrenia, while CSF HGF and S100B were positively correlated with psychotic symptom and CSF IL‐11, IL‐29/IFN‐λ1, and TSLP were negatively correlated. Increased CSF IFN‐β and IL‐1β and decreased CSF Aβ42, APP, IL‐6, and NCAM‐1 were observed, while CSF S100B was positively correlated with manic symptom in patients with BD. Increased CSF IL‐4, MCP‐1, MIP‐1β, and MMP‐2 were observed in patients with MDD, while CSF HGF and MMP‐2 were positively correlated with depressive symptom and CSF IL‐15 and MCP‐1 were negatively correlated. However, signal cross‐talk and cross‐reactivity problems have been observed in previous studies using multiplex immunoassay. The proximity extension assay can be used to overcome cross‐reactivity and enable ultrasensitive multiplexed detection and quantification of more than 1000 target proteins. However, proteomic studies using proximity extension assay technology in patients with schizophrenia, BD, or MDD are still scarce. Therefore, future high‐quality proteomic studies are required to identify CSF biomarkers for larger sets of target proteins in patients with major psychiatric disorders. [ABSTRACT FROM AUTHOR]

Aims: To investigate the negative attitudes of Japanese psychiatrists toward atypical long‐acting injectable (LAI) antipsychotics, which are the current mainstream LAIs in Japan. Methods: We surveyed 69 Japanese psychiatrists using a 5‐point Likert scale to assess their attitudes toward atypical LAI antipsychotics. Our assessment referenced concerns identified in a study conducted in Japan a decade ago, which found significant differences when compared with a survey of German psychiatrists. We also identified the factors influencing these negative attitudes. Additionally, the results were compared with those of previous Japanese and German studies. Results: More than 50% of Japanese psychiatrists expressed negative attitudes toward atypical LAI antipsychotics in various areas. These concerns included apprehensions about cost, reluctance to recommend them initially, pain from injections, complexity of switching to LAI, usage in first‐episode cases, and sufficient medication adherence with oral drugs. In all three studies, cost and adequate adherence to oral medication were concerns that exceeded the average of the three negative comments. Age and experience in psychiatry influenced the psychiatrists' attitudes toward using these drugs in first‐episode cases. Conclusions: These findings shed light on the reasons for the underutilization of atypical LAI antipsychotics and suggest opportunities to enhance their appropriate use in clinical settings. [ABSTRACT FROM AUTHOR]

Aim: Manipulation of the intestinal microbiome and supplying vitamin D can attenuate psychiatric symptoms in schizophrenic patients. The current study tried to evaluate the effects of probiotic/vitamin D supplementation on the cognitive function and disease severity of schizophrenic patients. Methods: In the present study, 70 patients (aged 18–65) with schizophrenia were recruited. Participants were randomly allocated to the placebo (n = 35) and intervention (probiotic supplements+400 IU vitamin D, n = 35) groups. Severity of disease and cognitive function (primary outcomes) were evaluated by Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MoCA) tests, respectively. Moreover, lipid profile, body mass index (BMI), gastrointestinal (GI) problems, serum C‐reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated as secondary outcomes. Results: A total of 69 patients completed the study. The MoCA score was increased by 1.96 units in the probiotic‐containing supplement group compared to the placebo (p = 0.004). Also, the percentage of subjects with MoCA score ≥ 26 rose significantly in the intervention group (p = 0.031). Moreover, TC (p = 0.011), FBS (p = 0.009), and CRP (p < 0.001) significantly decreased in the supplement group compared to the placebo. Although the probiotic supplement reduced PANSS score by 2.82 units, the difference between the study groups was not statistically significant (p = 0.247). Conclusion: Co‐administration of probiotics and vitamin D has beneficial effects on the improvement of cognitive function in schizophrenic patients. [ABSTRACT FROM AUTHOR]

Aim: Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities. Methods: We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain. Results: We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions. Conclusions: When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions. [ABSTRACT FROM AUTHOR]

Mismatch negativity (MMN) is an event‐related potential component automatically elicited by events that violate predictions based on prior events. To elicit this component, researchers use stimulus repetition to induce predictions, and the MMN is obtained by subtracting the brain response to rare or unpredicted stimuli from that of frequent stimuli. Under the Predictive Processing framework, one increasingly popular interpretation of the mismatch response postulates that MMN represents a prediction error. In this context, the reduced MMN amplitude to auditory stimuli has been considered a potential biomarker of Schizophrenia, representing a reduced prediction error and the inability to update the mental model of the world based on the sensory signals. It is unclear, however, whether this amplitude reduction is specific for auditory events or if the visual MMN reveals a similar pattern in schizophrenia spectrum disorder. This review and meta‐analysis aimed to summarise the available literature on the vMMN in schizophrenia. A systematic literature search resulted in 10 eligible studies that resulted in a combined effect size of g = −.63, CI [−.86, −.41], reflecting lower vMMN amplitudes in patients. These results are in line with the findings in the auditory domain. This component offers certain advantages, such as less susceptibility to overlap with components generated by attentional demands. Future studies should use vMMN to explore abnormalities in the Predictive Processing framework in different stages and groups of the SSD and increase the knowledge in the search for biomarkers in schizophrenia. [ABSTRACT FROM AUTHOR]

Abnormal reward processing and psychomotor slowing are well‐known in schizophrenia (SZ). As a slow frontocentral potential, contingent negative variation (CNV) is associated with anticipatory attention, motivation and motor planning. The present study aims to evaluate the early and late amplitude and latencies of CNV in patients with SZ compared to healthy controls during a reward processing task and to show its association with clinical symptoms. We recruited 21 patients with SZ and 22 healthy controls to compare early and late CNV amplitude and latency values during a Monetary Incentive Delay (MID) Task between groups. Patients' symptom severity, levels of negative symptoms and depressive symptoms were assessed. Clinical features of the patients were further examined for their relation with CNV components. In conclusion, we found decreased early CNV amplitudes in SZ during the reward condition. They also displayed diminished and shortened late CNV responses for incentive cues, specifically at the central location. Furthermore, early CNV amplitudes exhibited a significant correlation with positive symptoms. Both CNV latencies were linked with medication dosage and the behavioural outcomes of the MID task. We revealed that early and late CNV exhibit different functions in neurophysiology and correspond to various facets of the deficits observed in patients. Our findings also emphasized that slow cortical potentials are indicative of deficient motivational processes as well as impaired reaction preparation in SZ. To gain a deeper understanding of the cognitive and motor impairments associated with psychosis, future studies must compare the effects of CNV in the early and late phases. [ABSTRACT FROM AUTHOR]

Most medical researchers and social scientists concur that mental illness is caused by "nature" and "nurture," yet efforts to reduce stigma tend to focus on biomedical causes. This study analyzed original survey data collected from 1,849 respondents in 2021–2022 who were randomly assigned to 16 experimental vignette conditions. Each vignette portrayed a man and varied according to which psychiatric diagnosis his situation resembled (alcohol dependence, depression, or schizophrenia) and what caused it: genetics (nature), environmental stress (nurture), or both. Control conditions included subclinical distress and no explanation. Exposure to the environmental explanation (vs. no explanation) predicted identifying mental illness, reduced expectation of violence toward others, increased willingness to socially interact, and optimism for recovery with treatment. Exposure to the nature and nurture explanation (vs. no explanation) predicted reduced desire for social distance. Implications of these findings for future research and for contact-based anti-stigma efforts are presented. [ABSTRACT FROM AUTHOR]

Aim: To develop a typology of care trajectories (CTs) 1 year before and after a first dementia diagnosis in individuals aged ≥65 years, with prevalent schizophrenia or bipolar disorder. Methods: This was a longitudinal, retrospective cohort study using health administrative data (1996–2016) from Quebec (Canada). We selected patients aged ≥65 years with an incident diagnosis of dementia between 1 January 2014 and 31 December 2016, and a diagnosis of schizophrenia and/or or bipolar disorder. A CT typology was generated by a multidimensional state sequence analysis based on the "6 W" model of CTs. Three dimensions were considered: the care setting ("where"), the reason for consultation ("why") and the specialty of care providers ("which"). Results: In total, 3868 patients were categorized into seven distinct types of CTs, with varying patterns of healthcare use and comorbidities. Healthcare use differed in terms of intensity, but also in its distribution around the diagnosis. For instance, whereas one group showed low healthcare use, healthcare use abruptly increased or decreased after the diagnosis in other groups, or was equally distributed. Other significant differences between CTs included mortality rates and use of long‐term care after the diagnosis. Most patients (67%) received their first dementia diagnosis during hospitalization. Conclusions: Our innovative approach provides a unique insight into the complex healthcare patterns of people living with serious mental illness and dementia, and provides an avenue to support data‐driven decision‐making by highlighting fragility areas in allocating care resources. Geriatr Gerontol Int 2024; 24: 577–586. [ABSTRACT FROM AUTHOR]

Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem brain studies, and analyses from cellular models that recapitulate neurodevelopment. Emerging insights into schizophrenia genetic risk continue to converge on brain development, particularly stages of early brain development, that may be perturbed to deviate from a typical, normative course, resulting in schizophrenia clinical symptomatology. As the authors explicate, schizophrenia genetic risk is likely dynamic and context dependent, with effects of genetic risk varying spatiotemporally, across the neurodevelopmental continuum. Optimizing therapeutic strategies for the heterogeneous collective of individuals with schizophrenia may likely be guided by leveraging markers of genetic risk and derivative functional insights, well before the emergence of psychosis. Ultimately, rather than a focus on therapeutic intervention during adolescence or adulthood, principles of prediction and prophylaxis in the pre- and perinatal and neonatal stages may best comport with the biology of schizophrenia to address the early-stage perturbations that alter the normative neurodevelopmental trajectory. [ABSTRACT FROM AUTHOR]

Objectives: Working Alliance (WA) is important in the care of patients with Schizophrenia Spectrum Disorders (SSD). This study aims to determine which sociodemographic and clinical factors are associated with WA, as assessed by patients and staff members in Residential Facilities (RFs), and may predict WA dyads' discrepancies. Methods: Three hundred and three SSD patients and 165 healthcare workers were recruited from 98 RFs and characterized for sociodemographic features. WA was rated by the Working Alliance Inventory (WAI) for patients (WAIP) and staff members (WAI- T). SSD patients were assessed for the severity of psychopathology and psychosocial functioning. Results: Pearson's correlation revealed a positive correlation (ρ = .314; p < .001) between WAI- P and WAI- T ratings. Linear regression showed that patients with higher education reported lower WAI- P ratings (β = -.50, p = .044), while not being engaged in work or study was associated with lower WAI- T scores (β = -4.17, p = .015). A shorter lifetime hospitalization was associated with higher WAI- P ratings (β = 5.90, p = .008), while higher psychopathology severity negatively predicted WAI- T (β = -.10, p = .002) and WAI- P ratings (β = -.19, p < .001). Better functioning level positively foresaw WAI- T (β = .14, p < .001) and WAI- P ratings (β = .12, p < .001). Regarding discrepancies, staff members' age was associated with higher dyads discrepancy in Total scale and Agreement subscale scores, which were also associated with more severe negative symptoms, while patients' age was negatively correlated to Relationship subscale discrepancy. Conclusions: This study provides insight into the factors that influence WA in SSD patients and health workers in RFs. The findings address interventions to improve WA and ultimately patient outcomes. [ABSTRACT FROM AUTHOR]

The objective of the present systematic review is to answer the following question: is there enough scientific evidence to conclude that virtual reality is an effective tool to evaluate and treat the symptoms of people diagnosed with with schizophrenia? Eight systematic literature reviews and one meta-analysis focused on this question have recently been published. However, while they tend toward the conclusion that VR is of value in the evaluation and treatment of people diagnosed with schizophrenic disorders, they have important limitations. We used the PRISMA method. Using the keywords "virtual reality", "video game", "schizophrenia", "therapy" to search in four databases. 31 articles met our selection criteria (with independent double screening). We analyzed the objectives, methods, tools and results of each article. Twenty of the selected articles provide scientific evidence of the effectiveness of VR for evaluating different domains in schizophrenia. The other eleven articles focus on evidence of therapeutic effectiveness of interventions with VR tools. However, because of the diversity of the dimensions evaluated or treated, and of the VR tools used, replication studies are lacking. There is some scientific evidence that VR tools can be effective in the evaluation and treatment of dimensions of schizophrenia, in particular cognitive dimensions. However, additional studies are needed to confirm these results, replicating measures of the same dimensions using the same VR tools. [ABSTRACT FROM AUTHOR]

Research has shown that psychotic illness is more prevalent in frequent cannabis users, even though many people enjoy cannabis recreationally without major concerns. Therefore, understanding what creates vulnerability for dangerous cannabis use patterns and psychosis is of major importance. Psychological risk factors such as exposure to trauma/adversity and attachment style have been shown to create risk for both harmful patterns of cannabis use and psychosis. However, evidence regarding the individual and cumulative effects of these factors on psychosis onset and severity is lacking. Understanding the role of trauma and attachment in creating vulnerability for cannabis overuse might lead to incorporation of trauma and attachment-oriented therapies in the treatment of suitable individuals with early psychosis and cannabis misuse, and the development of more effective prevention. [ABSTRACT FROM AUTHOR]

Fear of relapse into psychosis is an independent risk factor for future relapse events, indicating its importance as a novel intervention target. Twenty-five participants responded to daily ecological momentary assessment prompts assessing common early warning signs of relapse and self-reported positive experiences like feeling supported by others. We conducted multilevel vector auto-regression using common symptoms assessed in early warning signs monitoring relapse prevention while controlling for positive self-reported experiences like feeling supported by others to estimate three networks (to explore concurrent, temporal and overall relationships). Reporting fear of relapse was positively associated (within the same cross-sectional time window) with hearing voices, alongside anxiety, negative affect and sleep change. Fear of relapse appeared to predict anxiety, negative affect and greater fear of relapse on the next consecutive day. However, none of the typical early warning signs predicted fear of relapse within the temporal window, and the observed relationships were small. Early warning signs appeared to be poor predictors of experiencing fear of relapse in this study. Fear of relapse predicts later anxiety and negative affect and may be a valuable intervention target within the daily life of people diagnosed with schizophrenia. [ABSTRACT FROM AUTHOR]

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder's clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation. [ABSTRACT FROM AUTHOR]

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions–Severity of Illness scale (CGI-SI) and Clinical Global Impressions–Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96–11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders. In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that clinical high risk for psychosis (CHR-P) is highly specific for psychotic disorders other than pluripotential to various serious mental illnesses. However, not all CHR-P develop psychotic disorder only, and psychosis can occur in non-psychotic disorders as well. Our prospective cohort study aims to investigate the characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders. The SPRIM study is a prospective naturalistic cohort program that focuses on the early detection of those at risk of developing serious mental illness, including psychosis (CHR-P), bipolar (CHR-B), and depressive disorder (CHR-D), as well as undifferentiated risk participants (UCHR). Our study has a longitudinal design with a baseline assessment and eight follow-up evaluations at 6, 12, 18, 24, 30, 36, 42, and 48 months to determine whether participants have transitioned to psychosis or mood disorders. The SPRIM sample consisted of 90 CHR participants. The total cumulative incidence rate of transition was 53.3% (95% CI 32.5–77.2). CHR-P, CHR-B, CHR-D, and UCHR had cumulative incidence rates of 13.7% (95% CI 3.4–46.4), 52.4% (95% CI 28.1–81.1), 66.7% (95% CI 24.6–98.6) and 54.3% (95% CI 20.5–93.1), respectively. The cumulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3% (95% CI 0.8–11.5), 45.7% (95% CI 24.4–73.6), and 11.2% (95% CI 3.1–36.2), respectively. Our study suggests that the concept of pluripotent high-risk for a diverse range of psychiatric disorders is an integrative approach to examining transdiagnostic interactions between illnesses with a high transition rate and minimizing stigma. • Characteristics and clinical outcomes of pluripotent high-risk group; potential for diverse psychiatric disorders. • The total cumulative incidence rate of transition was 53.3% (95% CI 32.5–77.2). • The cummulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3%, 45.7%, and 11.2%. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) represents a set of enduring mental illnesses whose underlying etiology remains elusive, posing a significant challenge to public health. Previous studies have shown that the neurodevelopmental process involving small molecules such as miRNA and mRNA is one of the etiological hypotheses of SCZ. We identified and verified that miR-30e-3p and ABI1 can be used as biomarkers in peripheral blood transcriptome sequencing data of patients with SCZ, and confirmed the regulatory relationship between them. To further explore their involvement, we employed retinoic acid (RA)-treated SH-SY5Y differentiated cells as a model system. Our findings indicate that in RA-induced SH-SY5Y cells, ABI1 expression is up-regulated, while miR-30e-3p expression is down-regulated. Functionally, both miR-30e-3p down-regulation and ABI1 up-regulation promote apoptosis and inhibit the proliferation of SH-SY5Y cells. Subsequently, the immunofluorescence assay detected the expression location and abundance of the neuron-specific protein β-tubulinIII. The expression levels of neuronal marker genes MAPT, TUBB3 and SYP were detected by RT-qPCR. We observed that these changes of miR-30e-3p and ABI1 inhibit the neurite growth of SH-SY5Y cells. Rescue experiments further support that ABI1 silencing can correct miR-30e-3p down-regulation-induced SH-SY5Y neurodevelopmental defects. Collectively, our results establish that miR-30e-3p′s regulation of neurite development in SH-SY5Y cells is mediated through ABI1, highlighting a potential mechanism in SCZ pathogenesis. [ABSTRACT FROM AUTHOR]

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients. • The dimensions of cognitive impairment were different in female DNS patients. • There are sex differences in NGAL and cognition in DNS patients. • Higher NGAL levels were a protective factor for cognition in female DNS patients. [ABSTRACT FROM AUTHOR]

Increased risk for somatic comorbidity in individuals with schizophrenia has been well established. In addition, psychiatric patients with somatic illnesses are more likely to have more psychiatric readmissions. Increased burden of treatment related to chronic somatic comorbidities may be associated with lower adherence to psychiatric medication. Cross-sectional study of 275 patients with schizophrenia spectrum disorder. A general practitioner performed a complete physical health checkup for all participants, including a complete medical examination and laboratory tests. Patients' adherence, attitudes, insight, and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment Scale. Overall symptomatology was measured using the Brief Psychiatric Rating Scale. Regression analysis was used to investigate interactions and associations among health beliefs, disease burden, and treatment adherence. Separate regression models were utilized to account for the complexity of health behavior and treatment adherence pathways. Patients' somatic comorbidity and health behavior were not associated with adherence or attitudes toward antipsychotic treatment. High dose of antipsychotics and obesity were related to the need for medical interventions, while a healthy diet reduced the risk. Higher BPRS score and older age were associated with having somatic symptoms. Somatic comorbidities had no negative effects on treatment adherence or attitudes. This study focuses on exploring possible associations between health beliefs and treatment adherence pathways in patients with psychotic disorders. Contrary to our hypotheses, we found no evidence to support our health belief and diseases burden models and their associations. [ABSTRACT FROM AUTHOR]

• Alpha oscillations propagate anterior-to-posterior in healthy controls in a behavioral task. • The propagation of alpha oscillations is disrupted in patients with schizophrenia. • Our results support the disconnection syndrome hypothesis regarding schizophrenia. Propagation of electroencephalogram (EEG) oscillations, often referred to as traveling waves, reflects the role of brain oscillations in neural information transmission. This propagation can be distorted by brain disorders such as schizophrenia that features disconnection of neural information transmission (i.e., disconnection syndrome). However, this possibility of the disruption of EEG oscillation propagation in patients with schizophrenia remains largely unexplored. Using a publicly shared dataset (N = 19 and 24; patients with schizophrenia and healthy controls, respectively), we investigated EEG oscillation propagation by analyzing the local phase gradients (LPG) of alpha (8–12 Hz) oscillations in both healthy participants and patients with schizophrenia. Our results showed significant directionality in the propagation of alpha oscillations in healthy participants. Specifically, alpha oscillations propagated in an anterior-to-posterior direction along mid-line and a posterior-to-anterior direction laterally. In patients with schizophrenia, some of alpha oscillation propagation were notably disrupted, particularly in the central midline area where alpha oscillations propagated from anterior to posterior areas. Our finding lends support to the hypothesis of a disconnection syndrome in schizophrenia, underscoring a disruption in the anterior-to-posterior propagation of alpha oscillations. This study identified disruption of alpha oscillation propagation observed in scalp EEG as a biomarker for schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: Among nursing home (NH) residents with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), racial/ethnic disparities in quality of care exist. However, little is known about quality of life (QoL). This study examines racial/ethnic differences in self-reported QoL among NH residents with AD/ADRD. Methods: Validated, in-person QoL surveys from 12,562 long-stay NH residents with AD/ADRD in Minnesota (2012–2015) were linked to Minimum Data Set assessments and facility characteristics. Hierarchical linear models assessed disparities in resident-reported mean QoL score (range, 0–100 points), adjusting for case-mix and facility factors. Results: Compared to White residents, racially/ethnically minoritized residents reported significantly lower total mean QoL scores (75.53 points vs. 80.34 points, p <.001). After adjustment for resident- and facility-level characteristics, significant racial/ethnic differences remained, with large disparities in food enjoyment, attention from staff, and engagement domains. Discussion: Policy changes and practice guidelines are needed to address racial/ethnic disparities in QoL of NH residents with AD/ADRD. [ABSTRACT FROM AUTHOR]

Introduction: Problem gambling (PBG) is more common in people with mental health disorders, including substance use, bipolar, and personality disorders, than in the general population. Although individuals with psychotic disorders might be expected to be more vulnerable to PBG, fewer studies have focused on this comorbidity. The aim of this review was to estimate the prevalence of PBG in people with psychotic disorders. Methods: Medline (Ovid), EMBASE, PsycINFO (Ovid), CINAHL, CENTRAL, Web of science, and ProQuest were searched on November 1, 2023, without language restrictions. Observational and experimental studies including individuals with psychotic disorders and reporting the prevalence of PBG were included. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal for systematic reviews of prevalence data. The pooled prevalence of PBG was calculated using a fixed effects generalized linear mixed model and presented through forest plots. Results: Of 1271 records screened, 12 studies (n = 3443) were included. The overall prevalence of PBG was 8.7% (95% CI = 7.8%–9.7%, I2 = 69%). A lower prevalence was found in studies with a low risk of bias (5.6%; 95% CI = 4.4%–7.0%) compared with studies with a moderate risk of bias (10.4%; 95% CI = 9.2%–11.7%). Different methods used to assess PBG also contributed to the heterogeneity found. Conclusion: This meta‐analysis found substantial heterogeneity, partly due to the risk of bias of the included studies and a lack of uniformity in PBG assessment. Although more research is needed to identify those at increased risk for PBG, its relatively high prevalence warrants routine screening for gambling in clinical practice. [ABSTRACT FROM AUTHOR]

Schizophrenia is a debilitating psychiatric disorder that can significantly affect a patient's quality of life and lead to permanent brain damage. Although medical research has identified certain genetic risk factors, the specific pathogenesis of the disorder remains unclear. Despite the prevalence of research employing magnetic resonance imaging, few studies have focused on the gene level and gene expression profile involving a large number of screened genes. However, the high dimensionality of genetic data presents a great challenge to accurately modeling the data. To tackle the current challenges, this study presents a novel feature selection strategy that utilizes heuristic feature fusion and a multi-objective optimization genetic algorithm. The goal is to improve classification performance and identify the key gene subset for schizophrenia diagnostics. Traditional gene screening techniques are inadequate for accurately determining the precise number of key genes associated with schizophrenia. Our innovative approach integrates a filter-based feature selection method to reduce data dimensionality and a multi-objective optimization genetic algorithm for improved classification tasks. By combining the filtering and wrapper methods, our strategy leverages their respective strengths in a deliberate manner, leading to superior classification accuracy and a more efficient selection of relevant genes. This approach has demonstrated significant improvements in classification results across 11 out of 14 relevant datasets. The performance on the remaining three datasets is comparable to the existing methods. Furthermore, visual and enrichment analyses have confirmed the practicality of our proposed method as a promising tool for the early detection of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: It is essential to assist individuals with a mental illness who have achieved clinical recovery in their personal recovery. Understanding the relationship between self‐stigma and social support and the effects on perceived recovery can be valuable for clinical professionals in helping patients lead meaningful lives. Aim: To examine the serial mediating roles of social support and perceived hope in self‐stigma and the effects on perceived recovery. Design: A cross‐sectional study. Methods: The study was conducted from September 2019 to June 2020. One hundred and fifty‐seven patients with schizophrenia in seven chronic rehabilitation wards were enrolled. Each patient had a Positive and Negative Syndrome Scale score ≤ 60 points, and they regularly participated in occupational rehabilitation. Research tools included demographic data, the Internalized Stigma of Mental Illness Scale (ISMIS), Multidimensional Scale of Perceived Social Support (MSPSS), Herth Hope Index (HHI), and Perceived Recovery Inventory (PRI). IBM SPSS 24.0 was used to analyse the data. Pearson correlation was used to analyse the relationships between variables, and models 4 and 6 of PROCESS macro V3.4 for SPSS were used to examine the mediation model. Results: The results indicated that self‐stigma and perceived recovery in patients with schizophrenia are negatively correlated, that peer support and perceived hope mediate the relationship between them, and that peer support and perceived hope also have a statistically significant serial mediating effect. Conclusion: The serial mediation effect of peer support and perceived hope on the relationship between self‐stigma and perceived recovery was statistically significant in this study. Impact: This research delves into strategies to assist psychiatric patients in reducing self‐stigma and achieving recovery. The findings underscore the heightened significance of peer support for patients in rehabilitative wards and offer valuable insights for medical staff. Reporting Method: STROBE checklist. Patient or Public Contribution: No patient or public contribution. [ABSTRACT FROM AUTHOR]

This study evaluated the association between rs1396409 and rs9883258 and the risk of schizophrenia (SCZ) and treatment outcomes in Egyptian patients. This study included 88 patients with SCZ and 88 healthy controls. Lipid profile was assayed. Genotyping of rs1396409 and rs9883258 polymorphisms was analyzed using real-time PCR. The rs1396409 AG genotype frequency was significantly associated with SCZ risk (p = 0.002). Also, significant increased risk of SCZ was observed under allelic (p = 0.001), dominant (p = 0.001) and overdominant (p = 0.001) genetic model of rs1396409. However, rs9883258 AA genotype revealed nonsignificant association with SCZ. Cases with the rs1396409AG genotype exhibited hypertriglyceridemia (p < 0.001) and hypercholesterolemia (p = 0.001). In total, 72.3% and 74.5% of the cases presented with rs1396409 AG have negative symptoms (p = 0.022) and exhibited poor drug response (p = 0.023), respectively; all cases with rs1396409 GG genotype attempted suicide (p = 0.002) and are drug-free (p = 0.003). SCZ patients with negative symptoms had hypercholesterolemia (p = 0.008) mainly low-density lipoproteins (LDLc) (p = 0.016), and those with cognitive symptoms presented with low level of high-density lipoprotein (HDLc) (p = 0.023). Moreover, the multivariate regression analysis revealed that both rs1396409 G allele and HDLc were predictors of SCZ (p = 0.003 and 0.001, resp.). The current study concluded that metabotropic glutamate receptor 7 (GRM7) rs1396409 AG could be a potential biomarker for SCZ diagnosis. It also revealed an independent association between the GRM7 rs1396409 G allele, HDLc and SCZ development. [ABSTRACT FROM AUTHOR]

Il s'agit d'étudier les enjeux psychopathologiques et socioculturels du TDI (Trouble Dissociatif de l'Identité), en lien avec la façon dont l'épidémie des « personnalités multiples » s'est dissoute à la fin du XXe siècle. Nous retraçons d'abord l'histoire du trouble dissociatif en revenant sur les critères diagnostiques du TDI (DSM-5 et CIM-11) pour les comparer avec ceux de l'ancien TPM (Trouble de la Personnalité Multiple) du DSM-III. Nous revenons ensuite sur le concept de « dissociation » en psychiatrie, en soulignant quelques difficultés de traduction et sa plurivocité. Puis, nous proposons de mobiliser le concept des effets de boucle (I. Hacking) pour rendre compte de l'évolution de la nosologie des classifications internationales. Enfin, nous concluons sur les enjeux de la pratique clinique auprès de patients concernés. Le changement de nomination du trouble dissociatif (de TPM à TDI) s'est effectué en réponse à des controverses médico-légales des années 1990. Pour autant, cette nouvelle étiquette diagnostique ne résout ni la problématique épistémologique autour de la dissociation (autour du différentiel névrose/psychose), ni la question des accompagnements thérapeutiques. Le TDI fait aujourd'hui l'objet de deux lectures opposées entre le modèle psychotraumatique et le modèle socio-cognitif. S'ils présentent des écarts et des conceptions irréconciliables de la dynamique des troubles psychiques, ils soulignent tous deux de nombreux points communs à propos du TDI. L'existence de la possibilité de cohabitation de différentes consciences, identités, ou personnalités n'est pas remise en cause. De même, la question du traumatisme est examinée par les tenants des deux modèles. Le succès du TDI pourrait ainsi être en partie expliqué comme un retour de la thèse initiale de la division subjective (Freud, Lacan), incompatible avec l'idée d'un moi fort unifié comme idéal de santé mentale. Pour autant, la logique de « boucle » propre aux classifications des troubles psychiques conduit à reconnaître au TDI une possibilité de nomination par les patients de certains de leurs symptômes. Ainsi, la question n'est pas de déterminer la supériorité d'un modèle « explicatif » du TDI mais d'examiner la dynamique qui a conduit le sujet à être identifié à ce diagnostic. Dans le cas que nous présentons, le TDI est lié à un vécu psychotique chez le patient. Le succès du TDI est contemporain d'interrogations sociales autour des questions d'identité. Les dynamiques du lien social propres au développement de nouvelles nominations ne peuvent cependant pas éclipser un certain réel de la folie se manifestant au travers de phénomènes dissociatifs. L'inconscient comme autre scène peut ainsi éclairer la logique de ces mécanismes, notamment en s'appuyant sur les outils du diagnostic structural proposés par la psychanalyse d'orientation lacanienne. Ces repérages permettent de préciser les conditions d'un accueil et d'une élaboration des troubles sous transfert pour les patients concernés. The aim is to examine the psychopathological and sociocultural implications of DID (Dissociative Identity Disorder), in relation to the way in which the epidemic of "multiple personalities" had dissipated by the end of the 20th century. We begin by tracing the history of dissociative disorder, reviewing the diagnostic criteria of DID (DSM-5 and ICD-11) and comparing them with those of the former MPD (Multiple Personality Disorder) in DSM-III. We then return to the concept of "dissociation" in psychiatry, highlighting some translation difficulties and its plurivocity. Finally, we conclude with a discussion of the issues involved in clinical practice with the patients concerned. The renaming of dissociative disorder (from MPD to DID) was a response to the forensic controversies of the 1990s. However, this new diagnostic label resolves neither the epistemological issues surrounding dissociation (around the neurosis/psychosis differential diagnosis), nor the question of therapeutic accompaniment. Today, DID is the subject of two opposing interpretations: the psychotraumatic model and the social-cognitive model. Although they present irreconcilable differences and conceptions of the dynamics of psychic disorders, they both emphasize many points in common with regard to DID. The possibility of the cohabitation of different consciousnesses, identities, or personalities is not called into question. Similarly, the issue of trauma is examined by proponents of both models. The success of the DID could thus be partly explained as a return to the initial thesis of subjective division (Freud, Lacan), incompatible with the idea of a strongly unified ego as an ideal of mental health. However, the "loop" logic inherent in the classification of psychological disorders means that DID can be seen as a way for patients to describe some of their symptoms. So, the question is not to determine the superiority of an "explanatory" model of DID, but to examine the dynamics that led the subject to be identified with this diagnosis. In the case presented here, DID is linked to the patient's psychotic experience. The success of DID is contemporaneous with social questioning around questions of identity. However, the dynamics of the social bond, specific to the development of a new vocabulary, cannot eclipse a certain reality of suffering manifested through dissociative phenomena. The unconscious as an "autre scène" can shed light on the logic of these mechanisms, notably by drawing on the tools of structural diagnosis proposed by Lacanian psychoanalysis. These insights help to define the conditions under which transference-related disorders can be accepted and elaborated for the patients concerned. [ABSTRACT FROM AUTHOR]

La psychothérapie institutionnelle reste un courant important pour quiconque travaille à l'hôpital ou en institution avec des patients souffrants de problématiques psychiatriques. Jean Oury en est le personnage principal et il a toujours défendu que toutes les idées et notions de la psychothérapie institutionnelle ne pouvaient se penser qu'en articulation avec une pratique au quotidien centrée sur la psychose de manière générale et sur la schizophrénie de manière particulière. Il nous a semblé dès lors intéressant de tenter de résumer la définition et la conception qu'Oury se faisait de la psychose et de la schizophrénie. C'est un travail dont la valeur est relative : Oury n'a jamais voulu faire un cours magistral sur le sujet et il refusait le discours universitaire. Son style et son enseignement principalement oral ne se prêtent pas à un résumé un peu scolaire. Néanmoins, il nous a semblé que l'exercice en valait la peine. En se basant sur de nombreuses citations, nous avons voulu synthétiser la position de Jean Oury. La nosologie sur laquelle s'appuie Oury est empruntée à la psychiatrie classique et n'est, à notre avis, pas la plus adéquate pour une clinique qui préconise l'accueil et la rencontre. Pour l'avenir de la psychothérapie institutionnelle, il est sans doute important de dissocier toutes les recommandations du mouvement pour soigner l'institution de la nosologie sur laquelle elles s'étayent. Seule la psychothérapie institutionnelle nous a appris à tenter de soigner les institutions de soins et à lutter contre la tendance naturelle de ces endroits à la ségrégation et aux rapports de force soignants-soignés. Mais une clinique de l'accueil et de la rencontre mérite mieux qu'une nosologie empruntée à la psychiatrie classique. Institutional psychotherapy remains an important current of thought for anyone working in hospitals or in institutions with patients suffering from psychiatric problems. Jean Oury is the main figure of this current and he always maintained that all the ideas and notions of institutional psychotherapy could only be thought of in conjunction with a daily practice centered on psychosis in general and on schizophrenia in particular. It therefore seemed interesting to us to try to summarize Oury's definition and conception of psychosis and schizophrenia. The value of our contribution is relative: Oury never wanted to give lectures on the subject and he refused the academic discourse. His style and his mainly oral teaching do not lend itself to a somewhat academic summary. Nevertheless, it seemed to us that the exercise was worth it. Based on numerous quotations, we wanted to synthesize Jean Oury's position. The nosology on which Oury relies is borrowed from classical psychiatry and is, in our opinion, not the most appropriate for a clinical practice that advocates reception and encounter. For the future of institutional psychotherapy, it is undoubtedly important to dissociate all the recommendations of the movement to heal the institution from the nosology on which they are based. Only institutional psychotherapy has taught us to try to heal care institutions and to fight against the natural tendency of these places to segregation and caregiver-patient power relations. But a clinical practice of reception and encounter deserves better than a nosology borrowed from classical psychiatry. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the effect of the therapeutic alliance on both change in social recovery outcomes and usage of a moderated online social therapy platform for first‐episode psychosis (FEP), Horyzons. Design: Secondary analysis of a single group pilot trial. Methods: Clients completed an alliance measure adapted for guided digital interventions at mid‐treatment. A series of multi‐level models evaluated change in outcomes by mid‐ and post‐treatment assessments (relative to baseline) as a function of the overall alliance. Quasi‐Poisson models evaluated the effect of the overall alliance on aggregated counts of platform usage. Exploratory analyses repeated these models in terms of the bond (human–human) or the task/goal (human–program) alliance. Results: Stronger overall alliance at mid‐treatment predicted lower loneliness at mid‐treatment and lower social anxiety at mid‐ and post‐treatment. It was also associated with higher completion of therapy activities and authoring of comments and reactions. A strong bond with an online therapist was associated with lower loneliness and higher perceived social support at mid‐treatment, lower social anxiety at post‐treatment as well as a higher number of reactions made on the social network. Stronger alliance with the platform's tasks and goals facilitated lower social anxiety at both follow‐up assessments and was further associated with higher completion of therapy activities and reactions in the social network. Conclusions: The alliance may impact aspects of social recovery and usage in digital interventions for FEP. Specific aspects of the alliance (human–human and human–program relationships) should be considered in future research. [ABSTRACT FROM AUTHOR]

Background: Disrupted metacognition is implicated in development and maintenance of negative symptoms, but more fine‐grained analyses would inform precise treatment targeting for individual negative symptoms. Aims: This systematic review identifies and examines datasets that test whether specific metacognitive capacities distinctly influence negative symptoms. Materials & Methods: PsycINFO, EMBASE, Medline and Cochrane Library databases plus hand searching of relevant articles, journals and grey literature identified quantitative research investigating negative symptoms and metacognition in adults aged 16+ with psychosis. Authors of included articles were contacted to identify unique datasets and missing information. Data were extracted for a risk of bias assessment using the Quality in Prognostic Studies tool. Results: 85 published reports met criteria and are estimated to reflect 32 distinct datasets and 1623 unique participants. The data indicated uncertainty about the relationship between summed scores of negative symptoms and domains of metacognition, with significant findings indicating correlation coefficients from 0.88 to −0.23. Only eight studies investigated the relationship between metacognition and individual negative symptoms, with mixed findings. Studies were mostly moderate‐to‐low risk of bias. Discussion: The relationship between negative symptoms and metacognition is rarely the focus of studies reviewed here, and negative symptom scores are often summed. This approach may obscure relationships between metacognitive domains and individual negative symptoms which may be important for understanding how negative symptoms are developed and maintained. Conlclusion: Methodological challenges around overlapping participants, variation in aggregation of negative symptom items and types of analyses used, make a strong case for use of Individual Participant Data Meta‐Analysis to further elucidate these relationships. [ABSTRACT FROM AUTHOR]

Clozapine is characterized by a large within‐ and between‐patient variability in its pharmacokinetics, attributed to non‐genetic and genetic factors. A cross‐sectional analysis of clozapine trough concentration (Clz C0) issued from Tunisian schizophrenic patients was collected and analysed using a nonparametric modelling approach. We assessed the impact of demographic covariates (age, weight and sex), patient's habits (smoking status, alcohol and caffeine intake) and the genetic factors (CYP1A2*1C, CYP1A2*1F and CYP2C19*2 polymorphisms) on each pharmacokinetic parameter. An external validation of this pharmacokinetic model using an independent data set was performed. Fit goodness between observed‐ and individual‐predicted data was evaluated using the mean prediction error (% MPE), the mean absolute prediction error (% MAPE) as a measure of bias, and the root mean squared error (% RMSE) as a measure of precision. Sixty‐three CLz C0 values issued from 51 schizophrenic patients were assessed in this study and divided into building and validation groups. CYP1A2*1F polymorphism and smoking status were the only covariates significantly associated with clozapine clearance. Precision parameters were as follows: 1.02%, 0.95% and 22.4%, respectively, for % MPE, % MAPE and % RMSE. We developed and validated an accurate pharmacokinetic model able to predict Clz C0 in Tunisian schizophrenic patients using the two parameters CYP1A2*1F polymorphism and smoking. [ABSTRACT FROM AUTHOR]

Schizophrenia is associated with increased risk of developing multiple aging-related diseases, including metabolic, respiratory, and cardiovascular diseases, and Alzheimer's and related dementias, leading to the hypothesis that schizophrenia is accompanied by accelerated biological aging. This has been difficult to test because there is no widely accepted measure of biological aging. Epigenetic clocks are promising algorithms that are used to calculate biological age on the basis of information from combined cytosine-phosphate-guanine sites (CpGs) across the genome, but they have yielded inconsistent and often negative results about the association between schizophrenia and accelerated aging. Here, we tested the schizophrenia-aging hypothesis using a DNA methylation measure that is uniquely designed to predict an individual's rate of aging. We brought together 5 case-control datasets to calculate DunedinPACE (Pace of Aging Calculated from the Epigenome), a new measure trained on longitudinal data to detect differences between people in their pace of aging over time. Data were available from 1812 psychosis cases (schizophrenia or first-episode psychosis) and 1753 controls. Mean chronological age was 38.9 (SD = 13.6) years. We observed consistent associations across datasets between schizophrenia and accelerated aging as measured by DunedinPACE. These associations were not attributable to tobacco smoking or clozapine medication. Schizophrenia is accompanied by accelerated biological aging by midlife. This may explain the wide-ranging risk among people with schizophrenia for developing multiple different age-related physical diseases, including metabolic, respiratory, and cardiovascular diseases, and dementia. Measures of biological aging could prove valuable for assessing patients' risk for physical and cognitive decline and for evaluating intervention effectiveness. [ABSTRACT FROM AUTHOR]

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity—as an index of the inhibitory function—was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity. [ABSTRACT FROM AUTHOR]

Physical activity (PA) is recommended to optimize well-functioning in people with schizophrenia. PA has been found to improve quality of life, general symptomatology, depression, anxiety and stress symptoms, global and social functioning. In PA research, most of the interventions are based on one-on-one interventions but there is poor information about group-based PA interventions. Using a randomized controlled, clinician-blinded trial, subjects are randomized into two arms: the PA group or control group. Our first objective is about to evaluate the effects of a multimodal 6 week collective PA intervention on depression, anxiety, and stress symptoms in people with schizophrenia. Our second objective is about to evaluate these effects on secondary outcomes especially smoking, well-being, physical fitness and on care utilization. All participants are evaluated before and after the 6 week intervention period, and only participants in the PA group are called in a follow-up interview 3 and 6 months after the intervention. Trial registration Individual Protection Committee of Ile-de-France II, n ID RCB: 2018- A00583-52. Registered on 8 April 2018. [ABSTRACT FROM AUTHOR]

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that, through its manipulation of endogenous oscillations, can affect cognition in healthy adults. Given the fact that both endogenous oscillations and cognition are impaired in various psychiatric diagnoses, tACS might represent a suitable intervention. We conducted a search of Pubmed and Web of Science databases and reviewed 27 studies where tACS is used in psychiatric diagnoses and cognition change is evaluated. TACS is a safe and well-tolerated intervention method, suitable for multiple-sessions protocols. It can be administered at home, individualized according to the patient''s anatomical and functional characteristics, or used as a marker of disease progression. The results are varying across diagnoses and applied protocols, with some protocols showing a long-term effect. However, the overall number of studies is small with a great variety of diagnoses and tACS parameters, such as electrode montage or used frequency. Precise mechanisms of tACS interaction with pathophysiological processes are only partially described and need further research. Currently, tACS seems to be a feasible method to alleviate cognitive impairment in psychiatric patients; however, a more robust confirmation of efficacy of potential protocols is needed to introduce it into clinical practise. [ABSTRACT FROM AUTHOR]

There is a pressing need for effective treatments that address the high rate of suicide observed among people with psychosis. In this scoping review we highlight two suicidogenic treatment targets that have been relatively neglected in people with psychotic disorders: emotional distress and emotion dysregulation. We review the research on these constructs in psychosis and their relationship to suicide in this population, and then make clinical recommendations based on research findings. Emotional distress and emotional dysregulation may be promising treatment targets for suicide among people with psychosis. [ABSTRACT FROM AUTHOR]

Objective: Clozapine is considered as the standard treatment for this subgroup, but the evidence is not unequivocal. There are several potential alternatives being used because of the possible adverse effects of clozapine. We aimed to examine the efficacy and adverse events of different antipsychotics in treatment-resistant schizophrenia by performing a network meta-analysis. Methods: We searched the Cochrane Schizophrenia Group register for randomized-controlled trials (up to March 06, 2022) and MEDLINE (up to January 20, 2023). We included blinded and open studies and participants with a broad definition of treatment resistance. The primary outcome was overall symptoms of schizophrenia; secondary outcomes were response to treatment, positive and negative symptoms of schizophrenia, discontinuation, side effects, quality of life, and functioning. The study was registered in Open Science Framework (https://osf.io/9nf2y/). Results: We included 60 studies involving 6838 participants in the network meta-analysis. In the primary outcome, clozapine and olanzapine were more efficacious than risperidone, haloperidol, fluphenazine, sertindole, chlorpromazine, and quetiapine (range of mean SMDs, − 0.11 to − 0.48). The difference between clozapine and olanzapine was trivial and uncertain (SMD − 0.05, 95% CI, − 0.21 to 0.11). The result of other efficacy outcomes as well as subgroup and sensitivity analyses were consistent with the primary analysis. Clozapine and olanzapine were associated with more weight gain, and clozapine was associated with more sedation events compared to many other antipsychotics. Conclusions: Clozapine remains the gold standard for patients with treatment-resistant schizophrenia. Olanzapine seems to be second-best and could be tried before switching to clozapine. [ABSTRACT FROM AUTHOR]

This study aimed to examine the efficacy of video games in improving cognitive function in chronic patients with schizophrenia and to evaluate the biomarker of video games for cognitive function. The patients in the game group were requested to play single-player video games on their smartphones for 1 h per day, five times a week for 6 weeks. Those in the control group watched television for 1 h per day, five times a week for 6 weeks. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop Color and Word Test (SCWT). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), General Self-Efficacy Scale (GSE), Problematic Mobile Gaming Questionnaire (PMGQ), and Patient Health Questionnaire-9 (PHQ-9). The game group demonstrated improved RBANS total score during the trial. There were no significant group effects among all SCWT scores. The game group demonstrated greater improvement on the PANSS Negative Scale, and global function (GAF score). The PMGQ scores were lower than the cutoff score at all time points in both groups. There were no significant group differences in the PHQ-9 and GSE scores. The serum BDNF levels were significantly higher in the game group following 6 weeks of video game intervention. The BDNF serum levels of all participants were positively associated with the RBANS total scores. This preliminary study suggested that video games can improve cognitive function in schizophrenia patients. Serum BDNF levels may be a suitable biomarker for predicting an improvement in cognitive function in schizophrenia patients. Trial registration: This study was registered on March 11, 2021 (ChiCTR2100044113). Clinical trials: Smartphone video games improve cognitive function in patients with chronic schizophrenia; https://www.chictr.org.cn/hvshowproject.aspx?id=95623; ChiCTR2100044113. [ABSTRACT FROM AUTHOR]

People with an intellectual disability have a higher risk of developing mental disorders compared to the general population. Available evidence suggests those with an intellectual disability receiving inpatient treatment in general psychiatric wards may have certain unique characteristics. Data gathered from a retrospective review of records of adults with intellectual disability admitted to general psychiatry wards in a tertiary psychiatric hospital in Singapore were analysed. Of 290 adults with intellectual disability, 62.8% were males. The median age was 38 years. The median length of stay was 12 days and over 80% had at least one previous admission. Nearly 80% had a mild intellectual disability and 64.5% had at least one psychiatric comorbidity, the majority having schizophrenia or psychotic disorder. Physical aggression was the most common primary reason for admission. The specific profile of patients identified in the study would be helpful in determining priority areas for the development of specialist psychiatric services for people with intellectual disability. [ABSTRACT FROM AUTHOR]

Psychiatric genetic counseling (pGC) can improve patient empowerment and self‐efficacy. We explored the relationship between pGC and psychiatric hospitalizations, for which no prior data exist. Using Population Data BC (a provincial dataset), we tested two hypotheses: (1) among patients (>18 years) with psychiatric conditions who received pGC between May 2010 and Dec 2016 (N = 387), compared with the year pre‐pGC, in the year post‐pGC there would be fewer (a) individuals hospitalized and (b) total hospital admissions; and (2) using a matched cohort design, compared with controls (N = 363, matched 1:4 for sex, diagnosis, time since diagnosis, region, and age, and assigned a pseudo pGC index date), the pGC cohort (N = 91) would have (a) more individuals whose number of hospitalizations decreased and (b) fewer hospitalizations post‐pGC/pseudo‐index. We also explored total days in hospital. Within the pGC cohort, there were fewer hospitalizations post‐pGC than pre‐ pGC (p = 0.011, OR = 1.69), and total days in hospital decreased (1085 to 669). However, when compared to matched controls, the post‐pGC/pseudo index change in hospitalizations among pGC cases was not statistically significant, even after controlling for the higher number of hospitalizations prior. pGC may lead to fewer psychiatric hospitalizations and cost savings; further studies exploring this are warranted. [ABSTRACT FROM AUTHOR]

Objective: We aimed at exploring the relationship between functional outcomes in patients on clozapine augmented with antipsychotics in treatment-resistant schizophrenia using standard outcome measures Health of Nation Outcome Scales (HoNOS) and Life Skills Profile (LSP-16). Method: In a cross-sectional study of 83 patients on clozapine treated in a psychiatric rehabilitation hospital, the association between the primary outcome measure, LSP-16 including its subscales, and treatment with antipsychotic augmentation (AA) were analysed using linear regression. Result: The presence of moderate-to-severe positive symptoms on the HoNOS 6 dichotomised item measure was the only statistically significant predictor of functional impairment as determined by total LSP-16 score. The group of patients with ongoing positive symptoms (partial responders) were characterised by higher total LSP-16 scores, higher numbers of AA agents, and higher chlorpromazine equivalence. There was an inverse linear relationship between chlorpromazine equivalence of AA and total score of LSP-16 scale in the group of partial responders. Conclusion: Augmentation with other antipsychotic agents was associated with higher functioning in a cross-sectional study of patients with schizophrenia with poor response of positive symptoms to clozapine. This might be an important clinical factor to consider when prescribing antipsychotics to patients with clozapine-resistant schizophrenia. [ABSTRACT FROM AUTHOR]

Accumulating evidence have shown that diet and nutrition play significant roles in mental illness, such as depression, anxiety and bipolar disorder. However, comprehensive evaluation of the relationship between nutrition and schizophrenia is lacking. The present review aims to synthetic elaborate the associations between nutrition and schizophrenia. Relevant studies on dietary patterns, macronutrients, micronutrients were performed through a literature search to synthesize the extracted data. Dietary interventions may help prevent the occurrence of schizophrenia, or delay symptoms: Healthy diets like nutritious plant-based foods and high-quality protein, have been linked to reducing the risk or symptoms of schizophrenia. Moreover, diet high in saturated fat and sugar is linked to more serious outcomes of schizophrenia. Additionally, when N-acetylcysteine acts as an adjuvant therapy, the overall symptoms of schizophrenia are significantly reduced. Also nascent evidence showed mental disorders may be related to intestinal microbiota dysfunction. Our study offered important insights into the dietary habits of patients with schizophrenia and the potential impact of nutritional factors on the disease. We also emphasized the need for further research, particularly in the form of large randomized double-blind controlled trials, to better understand the effects of nutrients on schizophrenia symptoms in different populations and disease types. [ABSTRACT FROM AUTHOR]

Dopamine β-hydroxylase (DBH) is a copper-containing enzyme that has an important role in maintaining the cellular homeostasis between the two neurotransmitters, dopamine (DA) and nor-adrenaline (NA). DBH functional polymorphisms are associated with multiple neuro-psychiatric conditions and are found to alter the DBH protein levels in serum affecting DBH enzymatic activity. The current study was conducted to determine the genetic and serum levels association of DBH rs1611115 functional polymorphism with major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SHZ) in the Pakistani population. In total n = 1097 subjects including MDD (n = 427), BD (n = 204), SHZ (n = 134) and healthy controls (n = 332), were screened for the functional polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression analysis was applied and the results were adjusted for age and sex. The DBH levels in serum were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied. The minor allele (-1021 C > T) was found to be significantly associated with a higher risk of developing BD and SHZ in both univariable and multivariable analyses. The overall total serum concentration of DBH was comparatively raised in MDD, however, in cross-comparison DBH serum levels were found markedly higher in CC homozygotes compared to TT homozygotes within the BD group. The present study suggested a significant association of DBH rs1611115 with BD and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BD for the first time in the Pakistani population. [ABSTRACT FROM AUTHOR]

[Display omitted] Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C–C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME. We found that schizophrenia-related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia-like behaviors. Moreover, among seven antipsychotic drugs, patients with the C-C (307Pro-851Ala) haplotype responded better to haloperidol than did the T-A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophrenia-related STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia-like phenotypes. [ABSTRACT FROM AUTHOR]

Patients with neurodevelopmental disorders, such as autism spectrum disorder, often display abnormal circadian rhythms. The role of the circadian system in these disorders has gained considerable attention over the last decades. Yet, it remains largely unknown how these disruptions occur and to what extent they contribute to the disorders' development. In this review, we examine circadian system dysregulation as observed in patients and animal models of neurodevelopmental disorders. Second, we explore whether circadian rhythm disruptions constitute a risk factor for neurodevelopmental disorders from studies in humans and model organisms. Lastly, we focus on the impact of psychiatric medications on circadian rhythms and the potential benefits of chronotherapy. The literature reveals that patients with neurodevelopmental disorders display altered sleep–wake cycles and melatonin rhythms/levels in a heterogeneous manner, and model organisms used to study these disorders appear to support that circadian dysfunction may be an inherent characteristic of neurodevelopmental disorders. Furthermore, the pre‐clinical and clinical evidence indicates that circadian disruption at the environmental and genetic levels may contribute to the behavioural changes observed in these disorders. Finally, studies suggest that psychiatric medications, particularly those prescribed for attention‐deficit/hyperactivity disorder and schizophrenia, can have direct effects on the circadian system and that chronotherapy may be leveraged to offset some of these side effects. This review highlights that circadian system dysfunction is likely a core pathological feature of neurodevelopmental disorders and that further research is required to elucidate this relationship. [ABSTRACT FROM AUTHOR]