Predictors of transition to schizophrenia and other long-lasting non-affective psychoses in first-episode patients with acute and transient psychotic disorders: A validation study

Background and objectives Almost half of the individuals with a first-episode of psychosis who initially meet criteria for acute and transient psychotic disorder (ATPD) will have had a diagnostic revision during their follow-up, mostly toward schizophrenia. This study aimed to determine the proportion of diagnostic transitions to schizophrenia and other long-lasting non-affective psychoses in patients with first-episode ATPD, and to examine the validity of the existing predictors for diagnostic shift in this population. Methods We designed a prospective two-year follow-up study for subjects with first-episode ATPD. A multivariate logistic regression analysis was performed to identify independent variables associated with diagnostic transition to persistent non-affective psychoses. This prediction model was built by selecting variables on the basis of clinical knowledge. Results Sixty-eight patients with a first-episode ATPD completed the study and a diagnostic revision was necessary in 30 subjects at the end of follow-up, of whom 46.7% transited to long-lasting non-affective psychotic disorders. Poor premorbid adjustment and the presence of schizophreniform symptoms at onset of psychosis were the only variables independently significantly associated with diagnostic transition to persistent non-affective psychoses. Conclusion Our findings would enable early identification of those inidividuals with ATPD at most risk for developing long-lasting non-affective psychotic disorders, and who therefore should be targeted for intensive preventive interventions. (AU)

Does college education reduce the risk of schizophrenia? Evidence from a college enrollment expansion policy in China.

BACKGROUND: Schizophrenia occurs worldwide, and the health, and economic burden is substantial. As one of the common proxies of socioeconomic status (SES), education was reported to be associated with the risk of developing schizophrenia. However, there is no causal evidence about the relationship. This paper explores the health benefits of college education for schizophrenia. METHOD: Based on exogenous variation in college enrollment across regions and cohorts induced by college enrollment expansion policy, we use instrument variable (IV) estimate strategy to estimate impacts of college education on the risk of schizophrenia with the data from Second National Sample Survey on Disability. RESULTS: We find that college education reduces the risk of developing schizophrenia by 4.2 percentage points. Some further analyses suggest the causal protective effect is only found among men, rural, and low-income individuals. CONCLUSIONS: These findings provide new evidence for the causal relationship between college education and schizophrenia, and add to the literature on the health benefits of education.

N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia.

Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15-21); and 3) NAC treatment throughout all pregnancy (GD1-21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

Crossroads of methodological choices in research synthesis: insights from two network meta-analyses on preventing relapse in schizophrenia.

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry out several of its methodological and statistical steps is still lacking. Therefore, different working groups might often make different methodological choices based on their clinical and research experience, with possible advantages and shortcomings. In this contribution, we will critically assess two network meta-analyses on the topic of pharmacological prevention of relapse in schizophrenia, carried out by two different research groups. We will highlight the implications of different methodological choices on the analysis results and their clinical-epidemiological interpretation. Moreover, we will discuss some of the most relevant technical issues of network meta-analyses for which there is not a broad methodological agreement, including the assessment of transitivity.

Psychosis prediction 2.0: why child and adolescent mental health services should be a key focus for schizophrenia and bipolar disorder prevention research.

Existing approaches to psychosis prediction capture only a small minority of future cases. Recent research shows that specialist child and adolescent mental health services (CAMHS) offer a (previously unrecognised) high-risk and high-capacity approach for psychosis early identification, prediction and, ultimately, prevention.

Relapse prevention through health technology program reduces hospitalization in schizophrenia.

BACKGROUND: Psychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Here, we asked whether a technology-enhanced approach to relapse prevention could reduce days spent in a hospital after discharge. METHODS: The Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between 26 February 2013 and 17 April 2015 at 10 different sites in the USA in an outpatient setting. Patients were between 18 and 60 years old with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified. Patients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge. The health technology program included in-person, individualized relapse prevention planning with treatments delivered via smartphones and computers, as well as a web-based prescriber decision support program. The main outcome measure was days spent in a psychiatric hospital during 6 months after discharge. RESULTS: The study included 462 patients, of which 438 had complete baseline data and were thus used for propensity matching and analysis. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention followed by 349 participants (128 females) who received technology-enhanced relapse prevention. During 6-month follow-up, 43% of control and 24% of intervention participants were hospitalized (χ2 = 11.76, p<0.001). Days of hospitalization were reduced by 5 days (mean days: b = -4.58, 95% CI -9.03 to -0.13, p = 0.044) in the intervention condition compared to control. CONCLUSIONS: These results suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.

[New challenge for services for people with a first episode of psychosis: To integrate interventions to prevent and reduce physical aggression]. / Le nouveau défi des services destinés aux personnes présentant un premier épisode de psychose : intégrer des interventions pour prévenir et réduire les agressions physiques.

Objective Mental health services for persons presenting a first episode of psychosis include specialized interventions that are effective in treating psychosis, but they do not include treatments that prevent aggressive behaviour (AB). This article presents the results of studies in an effort to incite these services to evaluate the risk of AB and to intervene rapidly to prevent these behaviours as well as treating the psychotic disorder. Method This article presents a narrative review of the scientific studies. We have reviewed publications in French and English reporting studies, reviews, and meta-analyses focused on the antecedents, correlates, and effective treatments for AB and criminality of persons described as presenting severe mental disorder, schizophrenia, or a first episode of psychosis. Results The review of scientific studies confirms that persons developing or presenting schizophrenia are at increased risk to engage in AB, crime, and homicide relative to the general population. Before a first episode of psychosis approximately one third of patients display AB. One subgroup of these persons, those who present the highest risk of AB and criminality, have a history of conduct disorder since childhood. Another subgroup who also begin engaging in AB before a first episode of psychosis display AB as anxiety and positive symptoms increase. The association between positive psychotic symptoms and AB varies according to the phase of illness and the age of onset of AB. Further, other factors such as substance misuse (especially cannabis use), difficulty in recognizing emotions in the faces of others, impulsivity, and physical victimization are related to AB. In addition to effective treatments for psychosis and social skill training, treatment programs aimed at preventing AB and antisocial behaviours, and the associated factors are needed, as well as interventions that aim to reduce victimization. Conclusion The extant literature identifies different profiles of patients and factors associated with AB that can be identified at a first episode of psychosis. Consequently, first episode services could play an important role in preventing AB. To do this, they would need to simultaneously treat the psychosis and the AB. The implementation of such treatments would involve challenges such as convincing treatment teams of the benefits of such an approach and convincing patients needing these treatments to comply. Increasing patients' motivation and compliance remains an important challenge.

Pharmacological interventions for prevention of weight gain in people with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem. OBJECTIVES: To determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia. SEARCH METHODS: The Cochrane Schizophrenia Information Specialist searched Cochrane Schizophrenia's Register of Trials on 10 February 2021. There are no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that examined any adjunctive pharmacological intervention for preventing weight gain in people with schizophrenia or schizophrenia-like illnesses who use antipsychotic medications. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed the quality of included studies. For continuous outcomes, we combined mean differences (MD) in endpoint and change data in the analysis. For dichotomous outcomes, we calculated risk ratios (RR). We assessed risk of bias for included studies and used GRADE to judge certainty of evidence and create summary of findings tables. The primary outcomes for this review were clinically important change in weight, clinically important change in body mass index (BMI), leaving the study early, compliance with treatment, and frequency of nausea. The included studies rarely reported these outcomes, so, post hoc, we added two new outcomes, average endpoint/change in weight and average endpoint/change in BMI. MAIN RESULTS: Seventeen RCTs, with a total of 1388 participants, met the inclusion criteria for the review. Five studies investigated metformin, three topiramate, three H2 antagonists, three monoamine modulators, and one each investigated monoamine modulators plus betahistine, melatonin and samidorphan. The comparator in all studies was placebo or no treatment (i.e. standard care alone). We synthesised all studies in a quantitative meta-analysis. Most studies inadequately reported their methods of allocation concealment and blinding of participants and personnel. The resulting risk of bias and often small sample sizes limited the overall certainty of the evidence. Only one reboxetine study reported the primary outcome, number of participants with clinically important change in weight. Fewer people in the treatment condition experienced weight gains of more than 5% and more than 7% of their bodyweight than those in the placebo group (> 5% weight gain RR 0.27, 95% confidence interval (CI) 0.11 to 0.65; 1 study, 43 participants; > 7% weight gain RR 0.24, 95% CI 0.07 to 0.83; 1 study, 43 participants; very low-certainty evidence). No studies reported the primary outcomes, 'clinically important change in BMI', or 'compliance with treatment'. However, several studies reported 'average endpoint/change in body weight' or 'average endpoint/change in BMI'. Metformin may be effective in preventing weight gain (MD -4.03 kg, 95% CI -5.78 to -2.28; 4 studies, 131 participants; low-certainty evidence); and BMI increase (MD -1.63 kg/m2, 95% CI -2.96 to -0.29; 5 studies, 227 participants; low-certainty evidence). Other agents that may be slightly effective in preventing weight gain include H2 antagonists such as nizatidine, famotidine and ranitidine (MD -1.32 kg, 95% CI -2.09 to -0.56; 3 studies, 248 participants; low-certainty evidence) and monoamine modulators such as reboxetine and fluoxetine (weight: MD -1.89 kg, 95% CI -3.31 to -0.47; 3 studies, 103 participants; low-certainty evidence; BMI: MD -0.66 kg/m2, 95% CI -1.05 to -0.26; 3 studies, 103 participants; low-certainty evidence). Topiramate did not appear effective in preventing weight gain (MD -4.82 kg, 95% CI -9.99 to 0.35; 3 studies, 168 participants; very low-certainty evidence). For all agents, there was no difference between groups in terms of individuals leaving the study or reports of nausea. However, the results of these outcomes are uncertain given the very low-certainty evidence. AUTHORS' CONCLUSIONS: There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain.

Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in Heterozygous Disc1 Mutant Mice, a Putative Prodromal Schizophrenia Animal Model.

Symptoms of schizophrenia (SZ) typically emerge during adolescence to young adulthood, which gives a window before full-blown psychosis for early intervention. Strategies for preventing the conversion from the prodromal phase to the psychotic phase are warranted. Heterozygous (Het) Disc1 mutant mice are considered a prodromal model of SZ, suitable for studying psychotic conversion. We evaluated the preventive effect of chronic N-acetylcysteine (NAC) administration, covering the prenatal era to adulthood, on the reaction following the Amph challenge, which mimics the outbreak or conversion of psychosis, in adult Het Disc1 mice. Biochemical and morphological features were examined in the striatum of NAC-treated mice. Chronic NAC treatment normalized the Amph-induced activity in the Het Disc1 mice. Furthermore, the striatal phenotypes of Het Disc1 mice were rescued by NAC including dopamine receptors, the expression of GSK3s, MSN dendritic impairments, and striatal PV density. The current study demonstrated a potent preventive effect of chronic NAC treatment in Disc1 Het mice on the acute Amph test, which mimics the outbreak of psychosis. Our findings not only support the benefit of NAC as a dietary supplement for SZ prodromes, but also advance our knowledge of striatal dopamine receptors, PV neurons, and GSK3 signaling pathways as therapeutic targets for treating or preventing the pathogenesis of mental disorders.

From the prodromal stage of multiple sclerosis to disease prevention.

A prodrome is an early set of signs or symptoms that indicate the onset of a disease before more typical symptoms develop. Prodromal stages are well recognized in some neurological and immune-mediated diseases such as Parkinson disease, schizophrenia, type 1 diabetes mellitus and rheumatoid arthritis. Emerging evidence indicates that a prodromal stage exists in multiple sclerosis (MS), raising the possibility of intervention at this stage to delay or prevent the development of classical MS. However, much remains unclear about the prodromal stage of MS and considerable research is needed to fully characterize the prodrome and develop standardized criteria to reliably identify individuals with prodromal MS who are at high risk of progressing to a diagnosis of MS. In this Roadmap, we draw on work in other diseases to propose a disease framework for MS that incorporates the prodromal stage, and set out key steps and considerations needed in future research to fully characterize the MS prodrome, identify early disease markers and develop standardized criteria that will enable reliable identification of individuals with prodromal MS, thereby facilitating trials of interventions to slow or stop progression beyond the prodrome.

Pretreatment with Carpolobia lutea ethanol extract prevents schizophrenia-like behavior in mice models of psychosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Carpolobia lutea decoction is widely used as a phytotherapeutic against central nervous system-related disorders including insomnia, migraine headache, and mental illness in West and Central Tropical Africa. AIM: This study was designed to investigate the antipsychotic activity of Carpolobia lutea (EECL) in mice models of psychosis. METHODS: Male Swiss mice (n = 5/group) were given EECL (100, 200, 400, and 800 mg/kg), haloperidol (1 mg/kg), clozapine (5 mg/kg) and vehicle (10 mL/kg) orally before amphetamine (5 mg/kg)-induced hyperlocomotion and stereotypy, apomorphine (2 mg/kg)-induced stereotypy, or ketamine (10, 30, and 100 mg/kg)-induced hyperlocomotion, enhancement of immobility and cognitive impairment. RESULTS: EECL (200, 400, and 800 mg/kg) prevented amphetamine- and apomorphine-induced stereotypies, as well as reduced hyperlocomotion induced by amphetamine and ketamine, all of which are predictors of positive symptoms. Regardless of the dose administered, EECL prevented the index of negative symptoms induced by ketamine. Furthermore, higher doses of EECL (400 and 800 mg/kg) also prevented ketamine-induced cognitive impairment, a behavioral phenotype of cognitive symptoms. CONCLUSION: Pretreatment with EECL demonstrated antipsychotic activity in mice, preventing amphetamine-, apomorphine-, and ketamine-induced schizophrenia-like symptoms, with 800 mg/kg being the most effective dose.

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia.

BACKGROUND: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. METHODS: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). FINDINGS: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). INTERPRETATION: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. FUNDING: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

BACKGROUND: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. OBJECTIVE: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? DESIGN: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. SETTINGS: Glasgow, UK, and Melbourne, Australia. PARTICIPANTS: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. INTERVENTIONS: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. MAIN OUTCOME MEASURES: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. RESULTS: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. LIMITATIONS: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. CONCLUSIONS: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. FUTURE WORK: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). TRIAL REGISTRATION: This trial is registered as ISRCTN99559262. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

WHAT WAS THE PROBLEM?: Relapse is a considerable problem for people with a diagnosis of schizophrenia. Relapse can be predicted by early warning signs that are unique to the person. They include withdrawal, fear and paranoia. WHAT WAS THE QUESTION?: Is it possible to investigate the effectiveness of an intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? WHAT DID WE DO?: We spoke with 88 mental health staff, 40 carers and 21 service users before we designed a system that used a mobile phone to help people monitor early warning signs. We included peer support to help people using the system reflect on their experiences. We hoped the overall system, called EMPOWER, would help people to be more in charge of their mental health. After consenting 86 people to the study, we were able to randomly assign 73 people either to use the EMPOWER system (42 people) or to receive their normal treatment alone (31 people). We used research measures over 1 year to help us better understand people's experiences. We also involved carers (for example family or friends) and mental health service providers in the research. WHAT DID WE FIND?: We found that it was possible to recruit people to the study and to gather research data. We also found that people used the EMPOWER system and found it acceptable. We found that those who used EMPOWER had a lower rate of relapse over 12 months than people who did not. They were also less likely to be fearful of relapse. We found that EMPOWER was likely to be cost-effective. WHAT DOES THIS MEAN?: This means that a study to investigate the effectiveness of a system to recognise and respond to early warning signs of relapse in schizophrenia is possible.

Supplementation of PQQ from pregnancy prevents MK-801-induced schizophrenia-like behaviors in mice.

RATIONALE: At present, the research on the prevention of schizophrenia is still in its infancy. Pyrroloquinoline quinone (PQQ) has potential to treat psychological and neurological diseases including schizophrenia. However, the preventive effect of PQQ on schizophrenia remains unclear. OBJECTIVES: In this study, we aimed to examine the preventive effect of supplementation of dietary PQQ from pregnancy or after birth on dizocilpine (MK-801)-induced schizophrenia-like behaviors in mice. RESULTS: Supplementation of dietary PQQ from pregnancy could effectively prevent MK-801-induced weight gain decrease, hyperlocomotion, stereotypical behavior, ataxia, exploratory activity decrease, social interaction disorder, memory deficit, and depression in mice. Supplementation of dietary PQQ after birth could effectively prevent MK-801-induced weight gain decrease, stereotypical behavior, ataxia, and memory deficit in mice. Female mice responded to a greater degree than males in preventing MK-801-induced weight gain decrease in both forms of PQQ supplementation. For mice that began PQQ supplementation after birth, females performed better than males in preventing MK-801-induced ataxia, memory deficit, and depression. For mice that began PQQ supplementation from pregnancy, males performed better than females in preventing MK-801-induced memory deficit. In vitro experiments indicated that PQQ supplementation in the earlier stage of life contributed to the growth of neurons and the development of neurites. CONCLUSIONS: Our current study suggested that PQQ supplementation from pregnancy or postpartum could prevent some schizophrenia-like behaviors induced by MK-801 in mice. Our work supported the potential usage of dietary supplement of PQQ in preventing or alleviating symptoms associated with schizophrenia.

Testing Efficacy of Relapse Prevention Intervention among Patients Diagnosed with Schizophrenia in Jordan.

Relapse prevention is an essential component in sustaining positive treatment outcomes.The purpose of this study was to test the efficacy of a relapse prevention intervention on the ability of patients and their primary caregivers to self-detect and manage early warning signs of relapse, and its impact on relapse rate among patients diagnosed with schizophrenia.Quasi-experimental design; one group posttest only, repeated measure time-series design was employed. A total of 40 patients and their primary caregivers represented the sample in this study.The statistical analysis revealed that the effect of relapse prevention intervention on patients and their primary caregivers' ability to self-detect severity and manage early warning signs of relapse has sustainable and positive effect on patients and their primary caregivers from T1 to T3 (patients, M = 9.0-9.3; caregivers, M = 9.7-9.9). Also, positive effect of intervention detected on abilities of patients and primary caregivers to manage EWS from T1 to T3 (patients, M = 35-36.0; caregivers, M = 39.7-38.1). The analysis also showed a low relapse rate (14.9%).The study showed that relapse prevention interventions is effective and applicable approach that psychiatric nurses can use to ensure sustainable positive outcomes of psychiatric healthcare among patients with schizophrenia.