First-episode Psychosis Research Articles

Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom–Dominant Psychosis

Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge. To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis. This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023. Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD. Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002). The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

GAPi: A description of the initiative for early psychosis intervention in Latin America and the short- to medium-term outcomes in early psychosis patients

IntroductionSchizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation. MethodsThe study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments. ResultsA total of 232 patients were enrolled in the cohort. Among them, 65.95 % completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research. DiscussionThe GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis. ConclusionThe GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries.

Breaking down processing speed: Motor and cognitive insights in first-episode psychosis and unaffected first-degree relatives

IntroductionProcessing speed (PS) deficits represent a fundamental aspect of cognitive impairment, evident not only in schizophrenia but also in individuals undergoing their first episode of psychosis (FEP) and their unaffected first-degree relatives. Heterogeneity in tests assessing PS reflects the participation of motor and cognitive subcomponents to varying degrees. We aim to explore differences in performance of the subcomponents of PS in FEP patients, parents, siblings, and controls. Materials and methodsResults from tests, including Trail Making Test part A and part B, Digit Symbol Coding Test, Grooved Pegboard Test, and Stroop Word and Stroop Color subtests, were obtained from 133 FEP patients, 146 parents, and 202 controls. Exploratory factor analysis (EFA) was employed in controls to establish the structure, followed by confirmatory factor analysis (CFA) to verify if the other groups share this structure. ResultsEFA revealed a two-factor model: Factor 1 for the motor subcomponent and Factor 2 for the cognitive subcomponent. Subsequently, CFA indicated a good fit for the remaining groups with differences in the relationship between the factors. ConclusionsDifferences in the relationships of factors within a common structure suggest the involvement of different compensatory strategies among groups, providing insights into the underlying mechanisms of PS deficits in patients and relatives.

Supporting people in Early Intervention in Psychosis services: the role of primary care.

Early Intervention in Psychosis (EIP) services offer treatment to people experiencing a first episode of psychosis. Service users may be referred from primary care and discharged directly back at the end of their time in an EIP service. To explore the role of primary care in supporting EIP service users (SUs) and to understand how to improve collaboration between primary and specialist care. Qualitative study comprising semi-structured interviews with SUs, carers, healthcare professionals (HCPs), managers, and commissioners. Interviews were conducted either online or by telephone. Thematic analysis was carried out using principles of constant comparison. Patient and public involvement were key to all stages, including data analysis. In total, 55 interviews were conducted with SUs (n = 13), carers (n = 10), and GPs, EIP HCPs, managers, and commissioners (n = 33). GPs reported difficulties in referring people into EIP services and little contact with SUs while in EIP services, even about physical health. GPs suggested they were not included in planning discharge from EIP to primary care. SUs and carers reported that transition from EIP can lead to uncertainty, distress, and exacerbation of symptoms. GPs reported only being made aware of patients on or after discharge, with no contact for 3 years. GPs described difficulty managing complex medication regimes, and barriers to re-referral to mental health services. GPs have a key role in supporting people within EIP services, specifically monitoring and managing physical health. Inclusion of GPs in planning discharge from EIP services is vital.

Neuromelanin-Sensitive MRI as Candidate Marker for Treatment Resistance in First-Episode Schizophrenia.

Markers for treatment resistance in schizophrenia are needed to reduce delays in effective treatment. Nigrostriatal hyperdopaminergic function plays a critical role in the pathology of schizophrenia, yet antipsychotic nonresponders do not show increased dopamine function. Neuromelanin-sensitive MRI (NM-MRI), which indirectly measures dopamine function in the substantia nigra, has potential as a noninvasive marker for nonresponders. Increased NM-MRI signal has been shown in psychosis, but has not yet been assessed in nonresponders. In this study, the authors investigated whether nonresponders show lower NM-MRI signal than responders. NM-MRI scans were acquired in 79 patients with first-episode psychosis and 20 matched healthy control subjects. Treatment response was assessed at a 6-month follow-up. An a priori voxel-wise analysis within the substantia nigra tested the relation between NM-MRI signal and treatment response in patients. Fifteen patients were classified as nonresponders and 47 patients as responders. Seventeen patients were excluded, primarily because of medication nonadherence or change in diagnosis. Voxel-wise analysis revealed 297 significant voxels in the ventral tier of the substantia nigra that were negatively associated with treatment response. Nonresponders and healthy control subjects had significantly lower NM-MRI signal than responders. Receiver operating characteristic curve analysis showed that NM-MRI signal separated nonresponders with areas under the curve between 0.62 and 0.85. In addition, NM-MRI signal in patients did not change over 6 months. These findings provide further evidence for dopaminergic differences between medication responders and nonresponders and support the potential of NM-MRI as a clinically applicable marker for treatment resistance in schizophrenia.

The association of adverse childhood experiences with long-term outcomes of psychosis: a 21-year prospective cohort study after a first episode of psychosis.

Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood. Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications. There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose-response relationship was observed between levels of CA and severity of outcome domains. Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

Glutamatergic neurotransmission in schizophrenia: A systematic review and quantitative synthesis of proton magnetic resonance spectroscopy studies across schizophrenia spectrum disorders.

Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across schizophrenia spectrum disorders. This systematic review employs qualitative and quantitative methods to analyse the patterns and relationships between glutamatergic metabolites, schizophrenia spectrum disorders and brain regions. A literature search was conducted using various databases with keywords including glutamate, glutamine, schizophrenia, psychosis and proton magnetic resonance spectroscopy. Inclusion criteria were limited to case-control studies that reported glutamatergic metabolite levels in adult patients with a schizophrenia spectrum disorder diagnosis - i.e. first-episode psychosis, schizophrenia, treatment-resistant schizophrenia and/or ultra-treatment-resistant schizophrenia - using proton magnetic resonance spectroscopy at 3 T or above. Pooled study data were synthesized and analysed. A total of 92 studies met the inclusion criteria, including 2721 healthy controls and 2822 schizophrenia spectrum disorder participants. Glu levels were higher in the basal ganglia, frontal cortex and medial prefrontal of first-episode psychosis participants, contrasting overall lower levels in schizophrenia participants. For Gln, strong differences in metabolite levels were evident in the basal ganglia, dorsolateral prefrontal cortex and frontal cortex, with first-episode psychosis showing significantly higher levels in the basal ganglia. In glutamate + glutamine, higher metabolite levels were found across schizophrenia spectrum disorder groups, particularly in the basal ganglia and dorsolateral prefrontal cortex of treatment-resistant schizophrenia participants. Significant relationships were found between metabolite levels and medication status, clinical measures and methodological variables. The review highlights abnormal glutamatergic metabolite levels throughout schizophrenia spectrum disorders and in specific brain regions. The review underscores the importance of standardized future research assessing glutamatergic metabolites using proton magnetic resonance spectroscopy due to considerable literature heterogeneity.

Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

Neuropsychological profiles in first-episodes psychosis and their relationship with clinical, metacognition and social cognition variables.

An increasing interest in the assessment of neuropsychological performance variability in people with first-episode psychosis (FEP) has emerged. However, its association with clinical and functional outcomes requires further study. Furthermore, FEP neuropsychological subgroups have not been characterized by clinical insight or metacognition and social cognition domains. The aim of this exploratory study was to identify specific groups of patients with FEP based on neuropsychological variables and to compare their sociodemographic, clinical, metacognition and social cognition profiles. A sample of 149 FEP was recruited from adult mental health services. Neuropsychological performance was assessed by a neuropsychological battery (WAIS-III; TMT; WSCT; Stroop Test; TAVEC). The assessment also included sociodemographic characteristics, clinical, functional, metacognition and social cognition variables. Two distinct neuropsychological profiles emerged: one neuropsychological impaired cluster (N = 56) and one relatively intact cluster (N = 93). Significant differences were found between both profiles in terms of sociodemographic characteristics (age and level of education) (p = 0.001), clinical symptoms (negative, positive, disorganized, excitement and anxiety) (p = 0.041-0.001), clinical insight (p = 0.038-0.017), global functioning (p = 0.014), as well as in social cognition domains (emotional processing and theory of mind) (p = 0.001; p = 0.002). No significant differences were found in metacognitive variables (cognitive insight and 'jumping to conclusions' bias). Relationship between neurocognitive impairment, social cognition and metacognition deficits are discussed. Early identifying of neuropsychological profiles in FEP, characterized by significant differences in clinical and social cognition variables, could provide insight into the prognosis and guide the implementation of tailored early-intervention.

Clinical presentation of first episode psychosis in people with and without HIV in KwaZulu-Natal, South Africa.

Mental disorders and HIV are the main contributors to the increase in years lived with disability rates per person in sub-Saharan Africa. A complex inter-relationship exists between HIV and mental illness, especially in a region with a high HIV prevalence. We examined the duration of untreated psychosis (DUP), and the nature of psychotic and cognitive symptoms in people with first episode psychosis (FEP) living with and without HIV. Adults aged between 18 and 45 years were assessed using a clinical interview, physical examination and several psychiatric tools. These included the Mini International Neuro-psychiatric Interview to confirm psychosis, Positive and Negative Syndrome Scale, International HIV Dementia Scale and other scales to measure symptom variables. HIV ELISA was used for HIV serology testing, with measures being carried out within 6 weeks of the first presentation. Of the 172 people presenting with FEP, 36 (21%) had comorbid HIV, those with both being older and more likely to be female (p < .001). Clinically, participants with FEP and HIV scored lower on the positive subscale (p = .008). There were no statistically significant differences for DUP or cognitive screening. Of those living with HIV and FEP (n = 36) comorbidity, nine were newly diagnosed with HIV at the time of the study. Individuals presenting with FEP and comorbid HIV were older, female and reported more mood symptoms. The identification of nine new HIV infections also reflects the ongoing need to test for HIV in people presenting with severe mental illness.

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.

Association of gut dysbiosis with first‑episode psychosis (Review).

The gut‑microbiota‑brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut‑microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early‑life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first‑episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP.

Predicted Brain Age in First-Episode Psychosis: Association with Inexpressivity.

Accelerated brain aging is a possible mechanism of pathology in schizophrenia. Advances in MRI-based brain development algorithms allow for the calculation of predicted brain age (PBA) for individuals. Here, we assessed PBA in 70 first-episode schizophrenia-spectrum individuals (FESz) and 76 matched healthy neurotypical comparison individuals (HC) to determine if FESz showed advanced aging proximal to psychosis onset and whether PBA was associated with neurocognitive, social functioning, or symptom severity measures. PBA was calculated with BrainAgeR (v2.1) from T1-weighted MR scans. There were no differences in the PBAs between groups. After controlling for actual age, a "younger" PBA was associated with higher vocabulary scores among all individuals, while an "older" PBA was associated with more severe negative symptom "Inexpressivity" component scores among FESz. Female participants in both groups had an elevated PBA relative to male participants. These results suggest that a relatively younger brain age is associated with a better semantic memory performance. There is no evidence for accelerated aging in FESz with a late adolescent/early adult onset. Despite a normative PBA, FESz with a greater residual PBA showed impairments in a cluster of negative symptoms, which may indicate some underlying age-related pathology proximal to psychosis onset. Although a period of accelerated aging cannot be ruled out with disease course, it does not occur at the time of the first episode.

Identifying and managing treatment resistance early with the integration of a clozapine clinic within an early intervention for psychosis service.

Despite being the most effective antipsychotic medication for treatment-resistant psychosis, clozapine is often under-utilized with long delays to initiation. This study aimed to determine whether the integration of a clozapine clinic within an early intervention for psychosis service resulted in a change in the rate and time to initiation of clozapine, the number of trials of different antipsychotic medications prior to clozapine, community initiation and discontinuation rates. A clozapine clinic was established in the Early Psychosis Prevention and Intervention Centre in Melbourne. This was a pre- and post-evaluation study design. The 'clozapine clinic' cohort included those who commenced on clozapine from 01 January 2016 to 30 June 2018. Prior to the clozapine clinic, 24 young people commenced clozapine over the 30-month period compared to 36 in the clozapine clinic cohort (RR = 1.30, 95% CI: 0.75-2.28, p = .32). In the pre-clozapine clinic cohort, 4.6% of all those with a first episode of psychosis were commenced on clozapine compared to 6% in the clozapine clinic cohort. Prior to the clozapine clinic, the median time to the commencement of clozapine was 72 weeks (IQR: 38, 87), compared to 53.5 weeks (IQR: 38, 81.5) in the clozapine clinic (Z = -0.86, p = .393). The mean number of different antipsychotic medications prior to commencing clozapine remained stable at 3.2 (SD ± 1.1) in both cohorts (t = -0.20, p = .841). There was a lower rate of discontinuation in the clozapine clinic (43.5% vs. 14.7%, HR = 0.30, 95% CI: 0.09-0.98, p = .046). While this study was underpowered and there are limitations to the naturalistic study design, the findings lend support to the integration of a clozapine clinic within early intervention for psychosis services.

Corrigendum: Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis

Corrigendum: Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis

Relationship Between Exposure to Emotional Neglect and the Inflammatory Biomarkers Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, and Platelet-to-Lymphocyte Ratios in Patients With First-Episode Psychosis.

Relationship Between Exposure to Emotional Neglect and the Inflammatory Biomarkers Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, and Platelet-to-Lymphocyte Ratios in Patients With First-Episode Psychosis.

Social exclusion as a major outcome domain of psychotic disorders: early predictors, and associations with non-recovery and clinical staging 21years after a first episode of psychosis.

People with psychotic disorders have high levels of social exclusion; however, little is known about its early predictors. We present a long-term observational cohort study aimed at examining early risk factors for later social exclusion. A total of 243 subjects were assessed at their first psychotic episode for early risk factors including sociodemographic variables, familial risk of major mental disorders, perinatal complications, childhood factors, and adolescent factors and re-assessed after a mean follow-up of 21years for 12 social exclusion domains: leisure activities, housing, work, income, neighborhood deprivation, educational attainment, physical and mental health, family and social support, legal competence, and discrimination. The ability of risk factors to predict social exclusion was examined using hierarchical linear regression. Overall social exclusion was independently predicted by low parental socio-economic status, length of follow-up, familial risk of schizophrenia, obstetric complications, neurodevelopmental delay, poor childhood adjustment, childhood adversity, poor adolescent social networks, poor adolescent adjustment, and low premorbid IQ. The model explained 58.2% of the variance in total social exclusion score. Each social exclusion domain was predicted by a different set of variables, which explained between 17.8 and 57.0% of their variance, although low socio-economic status, familial risk of schizophrenia, obstetric complications, childhood adversity, and poor social networks predicted most of the social exclusion domains. Early risk factors strongly predicted later social exclusion. A multifaceted approach to preventing later social exclusion is crucial in people with a first episode of psychosis and early risk factors of social exclusion.

The Italian adaptation of the Mini-SIPS, a tool for early detection of individuals at clinical high risk and first episode of psychosis: A preliminary study of implementation in an Italian FEP program.

The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high risk (CHR) framework, the DSM-5 Attenuated Psychosis Syndrome (APS) and to be implemented in clinical settings. The Mini-SIPS was translated in Italian by a Yale-certified SIPS trainer, then back-translated in English by a trained psychologist, then approved by the Mini-SIPS authors. Since September 2021, the adapted Italian version of the Mini-SIPS has been implemented at the First Episode Psychosis (FEP) Program in Ferrara, Italy. The Italian version of Mini-SIPS was successfully administered to 15 individuals subsequently referred to the First Episode Psychosis service in Ferrara. Within this sample, the tool has proven to be both an effective and efficient tool for the identification of CHR and FEP, and a valid instrument to help with the differential diagnosis. It also performed as a valuable guide for retrieving information about psychiatric history, to date the onset of APS and/or full-blown psychosis, to track the progression from CHR to psychosis or to symptoms resolution and to describe patients' pathways to care. The Mini-SIPS is an efficient and easy-to-use interview to identify the early stages of psychosis and established psychosis in clinical contexts. The Italian adaptation of this interview could be effectively implemented in other Italian FEP Programs as a screening and monitoring tool. Formal validation of the instrument is needed to assessed validity and reliability in the diagnosis of the CHR and FEP.

A qualitative study of coping strategies and resilience in the aftermath of childhood adversity in first-episode psychosis.

Exposure to adversity during childhood is associated with elevated risk for commonly occurring forms of psychopathology, especially psychotic disorders. Despite the noteworthy consequences associated with adverse childhood experiences, an inconsistent and unpredictable number of at-risk populations present with remarkably good physical and mental health outcomes that can be attributed to resilience. This study aimed to qualitatively explore the experience of childhood adverse events and coping strategies employed by individuals that promote resilience and better mental health outcomes. Fourteen individuals with a history of childhood adversity were recruited to participate using a case-study approach. A semi-structured interview guide was developed based on empirical evidence and theoretical background, and the interviews were analysed using a reflexive thematic approach. Our findings showed that the type of adversity impacted the experience of trauma, for example, the death of a caregiver versus emotional abuse or witnessing violence at home. Five coping strategies were identified (social support, religious coping, problem or emotion-focused coping, and meaning-making), with healthy controls found to identify and use these resources more than the psychosis group to promote individual well-being and better mental health outcomes. Our findings provide insights into experiences in the aftermath of childhood adversity, emphasising the need to assess the history of trauma systematically. They further underscore the importance of mental health prevention programmes bolstering individual-level coping strategies and the resources available within our environments to help them manage adversity, improve overall outcomes, and promote resilience.

Development of Biomarkers Potentially Sensitive to Early Psychosis Using Mismatch Negativity (MMN) to Complex Pattern Deviations.

Infrequent stimulus deviations from repetitive sequences elicit mismatch negativity (MMN) even passively, making MMN practical for clinical applications. Auditory MMN is typically elicited by a change in one (or more) physical stimulus parameters (eg, pitch, duration). This lower-order simple MMN (sMMN) is impaired in long-term schizophrenia. However, sMMN contains activity from release from stimulus adaptation, clouding its face validity as purely deviance-related. More importantly, it is unreliably reduced in samples of first-episode psychosis, limiting its utility as a biomarker. Complex pattern-deviant MMN (cMMN) tasks, which elicit early and late responses, are based on higher-order abstractions and better isolate deviance detection. Their abstract nature may increase the sensitivity to processing deficits in early psychosis. However, both the early and late cMMNs are small, limiting separation between healthy and psychotic samples. In 29 healthy individuals, we tested a new dual-rule cMMN paradigm to assess additivity of deviance. Sounds alternated lateralization between left and right, and low and high pitches, creating a left-low, right-high alternating pattern. Deviants were a repeated left-low, violating lateralization and pitch patterns. Early and late cMMNs on the dual-rule task were significantly larger than those on the one-rule extra tone cMMN task (P < .05). Further, the dual-rule early cMMN was not significantly smaller than pitch or duration sMMNs (P > .48, .28, respectively). These results demonstrate additivity for cMMN pattern-violating rules. This increase in cMMN amplitude should increase group difference effect size, making it a prime candidate for a biomarker of disease presence at first psychotic episode, and perhaps even prior to the emergence of psychosis.