Treatment Of First-episode Psychosis Research Articles

Validating cognitive screening in young people with first-episode psychosis: The CogScreen protocol.

Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness-implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test-retest reliability and acceptability of two cognitive screening tools in young people with FEP. Participants will be 350 young people (aged 12-25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross-sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test-retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later. The protocol, rationale, and hypotheses for CogScreen are presented. CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP.

Systematic review of tobacco smoking prevalence among young people in treatment for first-episode psychosis.

To determine whether smoking prevalence in first-episode psychosis (FEP) is different than in people with established psychosis in long-term treatment. A systematic review of cross-sectional, case-control and cohort studies identified from searches of PubMed, Embase, CINAHL and PsycINFO up to 12 August 2023. 20 studies out of 2773 screened titles were included. There was no clear pattern of smoking by diagnosis as smoking rates in people with FEP ranged from 43% to 78%, while in those with established psychosis, it ranged from 19% to 76%. The wide range of smoking levels in both populations precluded conclusions as to whether smoking rates are different between people with FEP and established psychosis suggesting that factors other than the time course of the illness influence smoking levels.

A rapid review of literature on first episode psychosis among United States military service members

ABSTRACT Background Current literature does not thoroughly examine the development or treatment of first episode psychosis (FEP) among active duty service members. Methods We conducted a rapid review on demographics, epidemiology, assessment, and intervention for FEP among service members. The final dataset contained eight peer-reviewed articles published between 2011 and 2021. Results Incidence of FEP among service members ranged from 1.4 to 2.3 for schizophrenia and 5.6 to 9.3 for other psychotic disorders per 10,000 person-years. Risk factors for developing psychosis during active duty service included distance of the place of service to home, multiple substance use, birthplace or place of residence in small towns or large cities, psychosocial stress, placement in an Army service branch or motor transport occupation, and more than one visit to mental health providers in the year before diagnosis. Racial minority status, younger age, less education, lower military grade, less time spent in service, and never-married status were also associated with higher risk of FEP. Conclusion Enhancing screening procedures before and after military entrance, reducing the impact of psychosocial stress during military initiation, and providing early, multimodal treatment for FEP would likely improve health outcomes for service members and reduce burden on the Military Health System.

Stigma experienced as worse than symptoms of schizophrenia: A qualitative study about The OpusPanel.

Former patients and relatives of people who have received treatment in OPUS, a Danish specialized early intervention for first episode psychosis, have since 2009 worked to reduce stigma and increase hope related to schizophrenia and psychosis. They established The OpusPanel to share their own stories of living with an invisible disorder with new patients, health care professionals, politicians, and members of the public. The impact of The OpusPanel on stigma has not previously been explored or evaluated. The article aims to evaluate and gain an in-depth understanding of The OpusPanel's anti-stigma impact. In a qualitative design, 27 people with different affiliations to The OpusPanel were interviewed using semi-structured interview guides to capture their individual experiences of listening to, interacting with, or being part of The OpusPanel. Interview guides were constructed following a focus group interview with members of The OpusPanel. Analysis of the multi-perspectival dataset was facilitated through an interpretative phenomenological approach with investigator triangulation. Preliminary results were returned to the focus group members to ensure relevance and accuracy. The study found that almost all interviewees described a sense of hopefulness and decreased stigma after having experienced a member from The OpusPanel present their story or participating as panel members themselves. The findings suggest that attending presentations or participating in The OpusPanel reduces stigmatizing views about others or oneself. The study may inform The OpusPanel and similar initiatives for challenging stigma related to schizophrenia or psychosis.

First-episode psychosis intervention programme versus standard care for the clinical management of early phases of psychosis: cost analysis.

Early intervention programmes (EIPs) in psychosis have gained attention as specialised interventions to improve health-related and societal impacts for people with psychotic disorders. Previous studies have presented evidence in favour of EIPs over the first year of intervention, despite none considering the critical period before psychosis onset (5 years). To compare the associated costs of the First Episode Psychosis Intervention Program (CRUPEP) and treatment as usual (TAU) in a real-world cohort in a non-specialised psychiatric community setting. Direct and indirect mental health-related costs were calculated over 1 year and up to 7 years. Healthcare and societal costs were calculated from economic data related to the consumption of all healthcare resources, including emergency department attendances, hospital admissions, psychotropic medication prescriptions and societal costs. From a healthcare perspective, the intervention (CRUPEP) group initially showed a marginally higher cost per patient than the TAU group (€7621 TAU group v. €11 904 CRUPEP group) over the first year of follow-up. However, this difference was reversed between the groups on considering the entire follow-up, with the TAU group showing considerably higher associated costs per patient (€77 026 TAU v. €25 247 CRUPEP). The EIP (CRUPEP) showed clinical benefits and minimised the direct and indirect health-related costs of the management of psychosis. Although the CRUPEP intervention initially reported increased costs over 1 year, TAU surpassed the global costs over the entire follow-up.

Short-term disengagement from early intervention service for first-episode psychosis: findings from the "Parma Early Psychosis" program.

Service disengagement is a major concern for "Early Intervention in Psychosis" (EIP). Indeed, identifying predictors of engagement is crucial to maximize mental healthcare interventions in first-episode psychosis (FEP). No Italian study on this topic has been reported to date. Thus, the aims of this investigation were: (1) to examine short-term disengagement rate in an Italian population of FEP patients treated within an EIP service across a 1-year follow-up period, and (b) to assess the most relevant predictors of disengagement in the first year of treatment. All participants were young FEP help-seeking patients, aged 12-35years, enrolled within the "Parma Early Psychosis" (Pr-EP) protocol. At baseline, they completed the Positive And Negative Syndrome Scale (PANSS), the Health of the Nation Outcome Scale (HoNOS) and the Global Assessment of Functioning (GAF) scale. Univariate and multivariate Cox regression analyses were used. 496 FEP individuals were enrolled in this research. Across the follow-up, a 16.5% prevalence of short-term disengagement was found. Particularly robust predictors of service disengagement were poor baseline treatment non-adherence, living with parents and the presence of brief psychotic disorder or schizophreniform disorder at entry. About 16% of FEP patients disengaged the Pr-EP program within the first year of treatment. A solution to reduce disengagement and/or to favor re-engagement of these subjects might be to remain on EIP program caseloads allowing the option for low-intensity support and monitoring, also via remote technology.

The impact of early intervention for first episode psychosis on cognitive functioning.

Impaired cognitive functioning is a core characteristic of schizophrenia, present from the onset of the illness and relatively stable thereafter. Despite evidence supporting the impact of early intervention services (EIS) on improving symptoms and functioning in first episode psychosis (FEP), controlled research has not examined its impact on cognitive functioning. To evaluate the longitudinal course of cognitive functioning in FEP patients participating in a large, controlled study comparing EIS with usual services. A total of 404 persons ages 15-40years old with non-affective FEP participated in the Recovery After Initial Schizophrenia-Early Treatment Program. A cluster randomized controlled trial was conducted with 34 community mental health treatment centers across the U.S. randomized to provide either an EIS program (NAVIGATE) or usual Community Care (CC) to FEP patients for 2years. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline and 1- and 2-years later. Older participants (≥20years old) in both treatment groups improved on all BACS tests. Younger participants (15-19) in NAVIGATE improved significantly more on Digit Sequencing (working memory) than those in CC, whereas both groups improved on most of the other BACS tests. Improvements in cognitive functioning occurred mostly over the first year and were correlated with reductions in symptom severity. EIS do not improve cognitive functioning more than usual care for older FEP patients but may improve working memory in younger FEP patients. Interventions targeting cognition may be required to enhance cognitive functioning in most FEP patients.

A Functional Connectome-Based Neural Signature for Individualized Prediction of Antipsychotic Response in First-Episode Psychosis.

Identification of robust biomarkers that predict individualized response to antipsychotic treatment at the early stage of psychotic disorders remains a challenge in precision psychiatry. The aim of this study was to investigate whether any functional connectome-based neural traits could serve as such a biomarker. In a discovery sample, 49 patients with first-episode psychosis received multi-paradigm fMRI scans at baseline and were clinically followed up for 12 weeks under antipsychotic monotherapies. Treatment response was evaluated at the individual level based on the psychosis score of the Brief Psychiatric Rating Scale. Cross-paradigm connectivity and connectome-based predictive modeling were employed to train a predictive model that uses baseline connectomic measures to predict individualized change rates of psychosis scores, with model performance evaluated as the Pearson correlations between the predicted change rates and the observed change rates, based on cross-validation. The model generalizability was further examined in an independent validation sample of 24 patients in a similar design. The results revealed a paradigm-independent connectomic trait that significantly predicted individualized treatment outcome in both the discovery sample (predicted-versus-observed r=0.41) and the validation sample (predicted-versus-observed r=0.47, mean squared error=0.019). Features that positively predicted psychosis change rates primarily involved connections related to the cerebellar-cortical circuitry, and features that negatively predicted psychosis change rates were chiefly connections within the cortical cognitive systems. This study discovers and validates a connectome-based functional signature as a promising early predictor for individualized response to antipsychotic treatment in first-episode psychosis, thus highlighting the potential clinical value of this biomarker in precision psychiatry.

Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis.

Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population. PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5. Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42-8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05-12.65) vs 5.51 (4.73-6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration. In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered.

Point of care assay for blood aripiprazole concentrations: development, validation and utility.

The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

Should stressful life events be monitored after a first episode of psychosis?

In the 3 years following a first episode of psychosis, 50% of individuals will experience a relapse, which could be expressed as symptom exacerbation or readmission to a psychiatric inpatient unit. 1 Alvarez-Jimenez M Priede A Hetrick SE et al. Risk factors for relapse following treatment for first episode psychosis: a systematic review and meta-analysis of longitudinal studies. Schizophr Res. 2012; 139: 116-128 Crossref PubMed Scopus (312) Google Scholar Hence, finding the relevant risk factors for new episodes is an urgent matter in psychiatric research and clinical practice. Whereas risk factors such as substance misuse and non-adherence to medication are well understood and can be targeted by interventions, less is known about other factors that might also be important, such as sleep deprivation, depressive or manic symptoms, or stressful life events. 1 Alvarez-Jimenez M Priede A Hetrick SE et al. Risk factors for relapse following treatment for first episode psychosis: a systematic review and meta-analysis of longitudinal studies. Schizophr Res. 2012; 139: 116-128 Crossref PubMed Scopus (312) Google Scholar Among these factors, stressful life experiences are associated with an increased risk of developing psychosis in people who are already considered as having a high risk of psychosis. 2 Betz LT Penzel N Kambeitz-Ilankovic L et al. General psychopathology links burden of recent life events and psychotic symptoms in a network approach. NPJ Schizophr. 2020; 6: 40 Crossref PubMed Scopus (20) Google Scholar , 3 Mayo D Corey S Kelly LH et al. The role of trauma and stressful life events among individuals at clinical high risk for psychosis: a review. Front Psychiatry. 2017; 8: 55 Crossref PubMed Scopus (110) Google Scholar Therefore, it could be possible that stressful life experiences also affect the risk of relapses after the first episode of psychosis. Stressful life events and relapse of psychosis: analysis of causal association in a 2-year prospective observational cohort of individuals with first-episode psychosis in the UKThese results provide converging evidence of a causal effect of stressful life events on the risk of relapse in psychosis. They suggest that there is a need to develop interventions at the individual and health-service level that could mitigate the harmful effects of stressful life events. Full-Text PDF Open Access

Psychological/Personal recovery and its correlates in patients with first episode psychosis.

Recovery in psychosis is a multidimensional construct. The numbers of studies specially focusing on the recovery aspects in patients with first episode psychosis (FEP) are limited, with no study from India. Further, no study has looked specifically into the variables that affect recovery process in patients with FEP and little is known about factors which influence recovery in patients with FEP. To evaluate psychological recovery and its correlates in patients with FEP, currently in clinical remission. One hundred three patients of FEP in clinical remission were assessed on Recovery Assessment Scale (RAS), Positive and Negative Syndrome Scale for Schizophrenia, Calgary Depression Rating Scale for Schizophrenia, Negative Symptom Assessment 16, Rosenberg Self-esteem Scale, Social and Occupational Functioning Assessment Scale, the Alcohol, Smoking and Substance Involvement Screening Test, Beck Cognitive Insight Scale, Internalized Stigma of Mental Illness Scale, the Everyday discrimination Scale, Subjective Scale to Investigate Cognition in Schizophrenia and social cognitive deficits in theory of mind was evaluated on the Social Cognition Rating Tools in Indian Setting-Theory of Mind. The needs of the participants were assessed on the Camberwell Assessment of Needs - Research version and Supplemental Assessment of Needs. Coping, social support, medication adherence were also assessed by standardized scales. The mean weighted score was highest for goal and success orientation subscale followed by seeking and relying on social support, personal confidence and hope, overcome the illness and awareness and control over the illness as assessed by 41 items of the RAS. The main factors identified to affect psychological recovery in patients with FEP were duration of untreated psychosis, greater psychopathology, lower self-esteem, total unmet need, feeling of discrimination and stigmatization. The present study suggests that treatment of FEP should be started at the earliest and issues such as residual psychopathology, lower self-esteem, total unmet need, feeling of discrimination and stigma during the remission phase should be addressed by psychosocial interventions to promote psychological recovery in patients with first episode psychosis.

Investigation of momentary negative symptoms in patients with early psychosis in daily life: An experience sampling study

Negative symptoms are a key therapeutic target in promoting functional recovery in early psychosis intervention, but momentary negative symptom manifestations remain understudied in the early stage of illness. We employed an experience-sampling methodology (ESM) to evaluate momentary affective experiences, hedonic capacity for an event recalled, current activities and social interactions, and associated appraisals for 6 consecutive days in 33 clinically-stable early psychosis patients (within 3 years of treatment for first-episode psychosis) and 35 demographically-matched healthy controls. Adjusted multilevel linear-mixed models revealed higher intensity and variability of negative affect in patients than controls, but no group difference in affect instability as well as positive affect intensity and variability. Patients demonstrated no significantly greater anhedonia for event, activity or social interactions relative to controls. Higher preference for company (when alone) and to be alone (when in company) was observed in patients than controls. No significant group difference in pleasantness to be alone or proportion of time being alone. Our results indicate no evidence for blunting of affective experiences, anhedonia (social and non-social) and asociality in early psychosis. Future research complementing ESM with multiple digital phenotyping measures will facilitate more refined negative symptom assessment in the daily life of patients with early psychosis.

Stigma toward psychosis in urban Chile: Engaging "what matters most" to resist stigma through recovery-oriented services.

Stigma jeopardizes recovery and successful implementation of mental health services (MHS) globally. Despite cultural variation in how stigma manifests, few studies have examined how culture fundamentally impacts the concept of "personhood" in Latin America. Chile has expanded MHS, providing universal coverage for evaluation and treatment of first episode psychosis (FEP). We applied the "what matters most" (WMM) framework of stigma to identify culturally salient factors that shape or protect against stigma in urban Chile, identifying potential implications for MHS and recovery. In-depth interviews (n = 48) were conducted with MHS users with psychotic disorders (n = 18), their family members (n = 15), and community members (n = 15), from two urban regions in Chile. Interviews were coded and analyzed to identify WMM, how WMM shapes stigma, and how MHS can influence achieving WMM. Traditional values emphasizing physical/social appearance, gender roles, family, and social connectedness are highly valued. Socioeconomic transitions have engendered capitalistic variations on traditional values, with increasing emphasis on professional careers for men and women, individualism, and independence. Psychotic disorders interfere with fulfillment of both traditional and capitalist values, thereby reinforcing stigma. However, MHS are seen as partially effective in enabling fulfillment of some goals, including employment, appearance, and independence, while often remaining insufficient in enabling capacity to achieve marriage and having a family. MHS that facilitate recovery by engaging users in services, such as pharmacotherapy, education/vocational rehabilitation, and family-centered care aligned with cultural values can mitigate stigma and facilitate recovery by enabling users to fulfill WMM. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intervention Programs for First-Episode Psychosis: A Scoping Review Protocol

Early intervention programs for first-episode psychosis aim to intervene in the early stages of the disease. They are essential to prevent and delay the progression of the illness to a more advanced stage, but information about their characteristics is not systematized. The scoping review considered all studies of first-episode psychosis intervention programs, regardless of their context (hospital or community), and explored their characteristics. The scoping review was developed according to the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. The PCC mnemonic (population, concept, and context) addressed research questions, the inclusion and exclusion criteria, and the search strategy. The scoping review sought to identify the literature that meets the predefined inclusion criteria. The research was conducted in the following databases: Web of Science Core Collection, MEDLINE, CINAHL Complete and PsycINFO, Scopus, Cochrane Library, and JBI Evidence Synthesis. The search for unpublished studies included OpenGrey (a European repository) and MedNar. It used sources in English, Portuguese, Spanish, and French. It included quantitative, qualitative, and multi-method/mixed methods studies. It also considered gray or unpublished literature. After removing duplicates, two independent reviewers extracted the relevant information after selecting the articles. If there were disagreements, a third reviewer was used. The researchers have developed a tool based on the JBI model that will allow them to extract the relevant information for the review. The results are presented schematically in narratives and tables. This scoping review maps first-episode psychosis intervention programs by identifying their characteristics, participants, and specific implementation contexts and allows researchers to create multicomponent programs tailored to different contexts.

Predictors of treatment attrition of cognitive health interventions in first episode psychosis.

Dropping out of psychological interventions is estimated to occur in up to a third of individuals with psychosis. Given the high degree of attrition in this population, identifying predictors of attrition is important to develop strategies to retain individuals in treatment. We observed a particularly high degree of attrition (48%) in a recent randomized controlled study assessing cognitive health interventions for first-episode psychosis participants with comorbid social anxiety. Due to the importance of developing interventions for social anxiety in first episode psychosis, the aim of the present study was to identify putative predictors of attrition through a secondary analysis of data. Participants (n= 96) with first episode psychosis and comorbid social anxiety were randomized to receive cognitive behavioural therapy for social anxiety or cognitive remediation. Differences between completers and non-completers (<50% intervention completed) were compared using t-tests or chi-square analyses; statistically significant variables were entered into a multivariate logistic regression model. Non-completers tended to be younger, had fewer years of education and had lower levels of social anxiety compared to completers. Lower baseline social anxiety and younger age were statistically significant predictors of non-completion in the logistic regression model. Age and social anxiety were predictors of attrition in cognitive health interventions in first episode psychosis populations with comorbid social anxiety. In the ongoing development of social anxiety interventions for this population, future studies should investigate specific engagement strategies, intervention formats and outcome monitoring to improve participant retention in treatment.

A study on the pathway to care among patients with first episode psychosis attending a tertiary health care center in North Karnataka

ABSTRACT Context: Early treatment of schizophrenia and other psychotic disorders has a significant impact on the prognosis and outcome of these disorders. To reduce the time of untreated psychosis, it is necessary to know the help-seeking behavior and the path taken by the patients and their caregivers. Efforts at reducing the time to initiate treatment for first-episode psychosis (FEP) are very much needed. The pathway to care helps in determining various factors associated with the delay and also creates awareness regarding the negative pathway determinants. Aim: This study aims to find out the pathway to care in FEP. Settings and Design: This is a hospital-based, time-bound, cross-sectional study, conducted from January to June 2022 in the department of psychiatry of a tertiary health care center in North Karnataka. Subjects and Methods: Basic sociodemographic, clinical, and details related to pathway to care were collected using semi-structured pro forma. MINI plus 5.0.0 and International Classification of Diseases-10 DCR were used to assess and confirm the diagnosis. Brief Psychiatric Rating Scale was used to measure the severity of symptoms. Statistical Analysis: Data were compiled and appropriate statistical tests were used to analyze the data with the help of SPSS version 17.0. Results: Sixty-one cases of FEP were assessed. The majority (44.2%) of the cases were diagnosed with acute and transient psychotic disorders and 16.4% were schizophrenia. The median duration of untreated psychosis was 30 days (15–150 days). For the majority (54.1%) of the patients, first contact was faith healers and for 31.1%, it was mental health facilities. Conclusion: The most common pathway taken by the patients was faith healers as they were easily available in rural areas and free from stigma associated with mental illness. These findings can be utilized in making policies to increase awareness about mental health and also about the availability of mental health services.

Body mass index and metabolic changes following antipsychotic drug treatment of first-episode psychosis: influences of childhood trauma and tobacco smoking

Body mass index and metabolic changes following antipsychotic drug treatment of first-episode psychosis: influences of childhood trauma and tobacco smoking

Hemispheric lateralization of semantic processing before and after aripiprazole treatment in first-episode psychosis or ultra-high risk state

Whether aberrant language-related lateralization can be improved after antipsychotic treatment in drug-free patients with first-episode psychosis or ultra-high risk state is little known. We aimed to investigate the improvement in lateralization of semantic processing after antipsychotic treatment and associated clinical and cognitive changes. Twenty-one drug-free patients with first-episode psychosis or ultra-high risk state underwent functional magnetic resonance imaging with a semantic task, neuropsychological testing, and clinical assessments with the Positive and Negative Syndrome Scale before and after 6 weeks of aripiprazole treatment. A lateralization index of the region of interest, i.e., inferior frontal gyrus, was calculated and correlated with the behavioral indices of the semantic task, Positive and Negative Syndrome Scale scores, and language-related neuropsychological test scores. After treatment, the lateralization index of the inferior frontal gyrus was significantly increased, which was related to reduced activation of the right inferior frontal gyrus. The increase in the lateralization index was significantly associated with the increase in verbal fluency score. A higher baseline accuracy of the semantic task was associated with a higher post-treatment lateralization index of the inferior frontal gyrus and greater improvement of the total score and positive subscore of the Positive and Negative Syndrome Scale. Our findings indicated aripiprazole treatment significantly increased semantic processing-related lateralization in the inferior frontal gyrus in drug-free patients with first-episode psychosis or ultra-high risk state. A higher baseline accuracy might predict a higher post-treatment lateralization index and greater symptom improvement.

Anterior cingulate glutamate metabolites as a predictor of antipsychotic response in first episode psychosis: data from the STRATA collaboration

Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respond to standard antipsychotics could be fast-tracked to clozapine. Using proton magnetic resonance spectroscopy (1H-MRS), we examined the ability of glutamate and Glx (glutamate plus glutamine) in the anterior cingulate cortex (ACC) and caudate to predict response to antipsychotic treatment. A total of 89 minimally medicated patients with FEP not meeting symptomatic criteria for remission were recruited across two study sites. 1H-MRS and clinical data were acquired at baseline, 2 and 6 weeks. Response was defined as >20% reduction in Positive and Negative Syndrome Scale (PANSS) Total score from baseline to 6 weeks. In the ACC, baseline glutamate and Glx were higher in Non-Responders and significantly predicted response (P < 0.02; n = 42). Overall accuracy was greatest for ACC Glx (69%) and increased to 75% when symptom severity at baseline was included in the model. Glutamate metabolites in the caudate were not associated with response, and there was no significant change in glutamate metabolites over time in either region. These results add to the evidence linking elevations in ACC glutamate metabolites to a poor antipsychotic response. They indicate that glutamate may have utility in predicting response during early treatment of first episode psychosis. Improvements in accuracy may be made by combining glutamate measures with other response biomarkers.