First-episode Psychosis Group Research Articles

Vocational functioning in young people accessing services for first-episode psychosis and ultra-high risk of psychosis: A longitudinal naturalistic cohort study.

Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. This is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.

Sex differences in prolactin levels and clinical outcomes in patients with a first psychotic episode

AimTo analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP). MethodsWe measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex. ResultsProlactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline. ConclusionsProlactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

Plasma neurofilament light chain is not elevated in people with first-episode psychosis or those at ultra-high risk for psychosis

IntroductionNeurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data. MethodWe retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs). ResultsMean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (β = −0.22, 95 % CI [−0.86, 0.39], p = 0.516) nor UHR group (β = −0.37, 95 % CI [−0.90, 0.19], p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group. DiscussionOur study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders.

Anhedonia and suicidal ideation in young people with early psychosis: findings from a 2-year Italian follow-up study.

IntroductionHedonic deficits have been extensively studied in schizophrenia, but little is known about their association with suicidal ideation in early psychosis. Along the clinical staging of psychosis, also Ultra-High Risk (UHR) individuals are characterized by hedonic deficits, which are currently considered as putative predictors of both psychosis conversion and poor social/role functioning.ObjectivesThe aim of this research was to examine the relationship between anhedonia and suicidal thoughts across a 2-year follow-up period in people with First Episode Psychosis (FEP) and at Ultra High Risk (UHR) of psychosis.MethodsNinty-six UHR and 146 FEP, aged 13–35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Beck Depression Inventory-II (BDI-II). The BDI-II “Anhedonia” subscale score to assess anhedonia and the CAARMS “Depression” item 7.2 subscore to measure depression were used across the 2 years of follow-up. Hierarchical regression analyses were performed.ResultsNo difference in anhedonia scores between FEP and UHR individuals was found. In the FEP group, a significant enduring association between anhedonia and suicidal ideation was found at baseline and across the follow-up, independent of clinical depression. In the UHR subgroup, the enduring relationship between anhedonia and suicidal thoughts were not completely independent from depression severity.ConclusionsAnhedonia is relevant in predicting suicidal ideation in early psychosis. Specific pharmacological and/or psychosocial interventions on anhedonia within specialized EIP program could reduce suicide risk overtime.Disclosure of InterestNone Declared

Alteration in left frontoparietal connectivity correlates with impaired cognitive reappraisal in early psychosis

BackgroundImpaired cognitive reappraisal is a notable symptom of early psychosis, but its neurobiological basis remains underexplored. We aimed to identify the underlying neurobiological mechanism of this impairment by using resting-state functional connectivity (FC) analyses focused on brain regions related to cognitive reappraisal. MethodsResting-state functional magnetic resonance images were collected from 36 first-episode psychosis (FEP) patients, 32 clinical high-risk (CHR) individuals, and 48 healthy controls (HCs). Whole-brain FC maps using seed regions associated with cognitive reappraisal were generated and compared across the FEP, CHR and HC groups. We assessed the correlation between resting-state FC, reappraisal success ratio, positive symptom severity and social functioning controlling for covariates. ResultsFEP patients showed higher FC between the left superior parietal lobe and left inferior frontal gyrus than HCs. Higher FC between the left superior parietal lobe and left inferior frontal gyrus negatively correlated with the reappraisal success ratio in the FEP group after controlling for covariates. Lower FC correlated with lower positive symptom severity and improved global functioning in the FEP group. ConclusionsAlteration in left frontoparietal connectivity reflects impaired cognitive reappraisal in early psychosis, and such alteration correlates with increased positive symptoms and decreased global functioning. These findings offer a potential path for interventions targeting newly emerging symptoms in the early stages of psychosis.

Abnormal theta and alpha oscillations in children and adolescents with first-episode psychosis and clinical high-risk psychosis.

Cognitive control deficits are one of the main symptoms of psychosis. The basic neural oscillation patterns associated with cognitive control are already present in early adolescence. However, as previous studies have focused on adults with psychosis, it is unclear whether neurobiological impairments in cognitive control are present in children and adolescents with first-episode psychosis (FEP) or clinical high-risk (CHR) state for psychosis. To explore the deficits of electroencephalogram related to cognitive control tasks in children and adolescents with FEP and CHR. Electroencephalogram was recorded in untreated 48 patients with FEP, 24 patients with CHR and 42 healthy controls aged 10-17 years, while performing the visual oddball task. The N2 amplitude, theta and alpha oscillations were then analysed and compared between groups. There was no significant group difference in N2 amplitude (P = 0.099). All groups showed increased theta and alpha oscillations relative to baseline before the stimulus in the frontal, central, left fronto-central and right fronto-central areas. These changes differed significantly between groups, with the FEP group showing significantly smaller theta (P < 0.001) and alpha (P < 0.01) oscillation than healthy controls. Theta and alpha oscillations in the CHR group did not differ significantly from the FEP group and healthy controls. These results suggest that neural damage has already occurred in the early stage of psychosis, and that abnormal rhythmic activity of neurons may constitute the pathophysiological mechanism of cognitive dysfunction related to early-onset psychosis.

Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated. To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls. In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022. Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included. Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias. The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability. Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92). Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

Systematic Review and Meta-analysis: Rates of Violence During First-Episode Psychosis (FEP).

Most people with psychotic disorders will never commit an act of violence. However, the risk of violence committed by people with schizophrenia is higher than the general population. Violence risk is also known to be highest during the first episode of psychosis compared to later stages of illness. Despite this, there have been no comprehensive reviews conducted in the past 10 years examining rates of violence during FEP. We aimed to provide an updated review of the rate of violence in people with FEP. Meta-analytical techniques were used to identify pooled proportions of violence according to severity (less serious, serious, severe) and timing of violence (before presentation, at first presentation, after presentation to services). Twenty-two studies were included. The pooled prevalence was 13.4% (95% CI [9.0%-19.5%]) for any violence, 16.3% (95% CI [9.1%-27.4%]) for less serious violence, 9.7% (95% CI [5.4%-17.0%]) for serious violence and 2.7% for severe violence, regardless of time point. The pooled prevalence of any violence was 11.6% (95% CI [6.8%-18.9%]) before presentation, 20.8% (95% CI [9.8%-38.7%]) at first presentation and 13.3% (95% CI [7.3%-23.0%]) after presentation to services. Overall, rates of violence appear to be lower in more recent years. However, due to the high between-study heterogeneity related to study design, the findings must be interpreted with consideration of sample characteristics and other contextual factors. The prevalence of violence remained high at all-time points, suggesting that more targeted, holistic, and early interventions are needed for clinical FEP groups.

Changes in oscillatory patterns of microstate sequence in patients with first-episode psychosis

We aimed to utilize chaos game representation (CGR) for the investigation of microstate sequences and explore its potential as neurobiomarkers for psychiatric disorders. We applied our proposed method to a public dataset including 82 patients with first-episode psychosis (FEP) and 61 control subjects. Two time series were constructed: one using the microstate spacing distance in CGR and the other using complex numbers representing the microstate coordinates in CGR. Power spectral features of both time series and frequency matrix CGR (FCGR) were compared between groups and employed in a machine learning application. The four canonical microstates (A, B, C, and D) were identified using both shared and separate templates. Our results showed the microstate oscillatory pattern exhibited alterations in the FEP group. Using oscillatory features improved machine learning performance compared with classical features and FCGR. This study opens up new avenues for exploring the use of CGR in analyzing EEG microstate sequences. Features derived from microstate sequence CGR offer fine-grained neurobiomarkers for psychiatric disorders.

The short-, medium-, and long-term prevalence of physical health comorbidities in first-episode psychosis: a systematic review protocol

Background Individuals with first-episode psychosis (FEP) face an increased risk of physical comorbidities, notably cardiovascular diseases, metabolic disorders, respiratory disorders, and certain types of cancer. Previous reviews report pooled physical health prevalence from chronic psychosis and FEP groups. By contrast, this review will focus on antipsychotic-naïve FEP cohorts and incorporate data from observational longitudinal studies and antipsychotic intervention studies to understand the progression of physical health comorbidities from the onset to later stages of psychosis. This review aims to systematically examine the short-, medium-, and long-term period prevalence of these comorbidities in FEP and variations related to demographic factors. Methods A systematic review will be conducted using the PRISMA and MOOSE guidelines. Medline, Embase, PsycINFO, and CINAHL+, as well as Clinical Trials gov.uk, OpenGrey, WHO International Clinical Trials Registry Platform, Current Controlled Trials, United States National Institute of Health Trials Registry, and the Irish Health Repository, will be searched from inception. Longitudinal studies exploring physical health outcomes in FEP cohorts and antipsychotic intervention studies monitoring health outcomes in antipsychotic naïve FEP individuals will be eligible for inclusion. Two reviewers will independently screen titles, abstracts, and full-text articles. Bias in individual studies will be assessed using the JBI Critical Appraisal Checklist. A meta-analysis of the short-, medium-, and long-term prevalence of cardiovascular, metabolic, cancer, and respiratory outcomes and a narrative synthesis will be conducted. If possible, a meta-regression on the impact of demographic variables will be conducted. Conclusions This systematic review will clarify the progression of physical health comorbidities in FEP, informing early intervention strategies and policies for this population. Subsequent findings will be submitted to a leading journal, supplemented by a recovery education module for patient groups and a lay summary for wider dissemination. Registration The study was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42023431072; 17/06/2023).

Dysregulation of Microbiota in Patients With First-Episode Psychosis Is Associated With Symptom Severity and Treatment Response

BackgroundThe gut microbiome has been implicated in the pathogenesis of mental disorders where the gut-brain axis acts as a bidirectional communication network. MethodsHerein, we investigated the compositional and functional differences of gut microbiome between patients with first-episode psychosis (FEP) (n = 26) and healthy control participants (n = 22) using whole-genome shotgun sequencing. In addition, we assessed the oral microbiome in patients with FEP (n = 13) and listed their taxonomic diversity. ResultsOur findings suggest that there is a dysbiosis of gut microbiota in patients with FEP. Relative abundance of Bifidobacterium adolescentis, Prevotella copri, and Turicibacter sanguinis was markedly increased (linear discriminant analysis scores [log10] > 1, and Mann-Whitney U test; false discovery rate–adjusted p values < .05) in the FEP group compared with the healthy control participants. Pathway analysis indicated that several metabolic pathways, particularly deoxyribonucleotide biosynthesis, branched-chain amino acid biosynthesis, tricarboxylic acid cycle, and fatty acid elongation and biosynthesis, were dysregulated in the FEP group compared with the healthy control group. In addition, this preliminary study was able to identify specific gut microbes (at baseline) that were predictive of weight gain in the FEP group at a 1-year follow-up. Bacteroides dorei, Bifidobacterium adolescentis, Turicibacter sanguinis, Roseburia spp., and Ruminococcus lactaris were positively associated (eXtreme gradient boosting, XGBoost regression model, Shapley additive explanations, R2 = 0.82) with weight gain. ConclusionsOur findings may suggest the involvement of gut microbiota in the pathogenesis of psychosis. The benefit of modulation of the gut microbiome in the treatment of psychotic disorders should be explored further.

Proteomic profiling in the progression of psychosis: Analysis of clinical high-risk, first episode psychosis, and healthy controls

Background and hypothesisRecent evidence has highlighted the benefits of early detection and treatment for better clinical outcomes in patients with psychosis. Biological markers of the disease have become a focal point of research. This study aimed to identify protein markers detectable in the early stages of psychosis and indicators of progression by comparing them with those of healthy controls (HC) and first episode psychosis (FEP). Study designThe participants comprised 28 patients in the clinical high-risk (CHR) group, 49 patients with FEP, and 61 HCs aged 15–35 years. Blood samples were collected and analyzed using multiple reaction monitoring-mass spectrometry to measure the expression of 158 peptide targets. Data were adjusted for age, sex, and use of psychotropic drugs. Study resultsA total of 18 peptides (17 proteins) differed significantly among the groups. The protein PRDX2 was higher in the FEP group than in the CHR and HC groups and showed increased expression according to disease progression. The levels of six proteins were significantly higher in the FEP group than in the CHR group. Nine proteins differed significantly in the CHR group compared to the other groups. Sixteen proteins were significantly correlated with symptom severity. These proteins are primarily related to the coagulation cascade, inflammatory response, brain structure, and synaptic plasticity. ConclusionsOur findings suggested that peripheral protein markers reflect disease progression in patients with psychosis. Further longitudinal research is needed to confirm these findings and to identify the specific roles of these markers in the pathogenesis of schizophrenia.

54 The Influence of Sex on Cognitive Control Performance and Frontoparietal Network Integrity in First-Episode Psychosis

Objective:Cognitive deficits in first-episode psychosis (FEP) are well documented, particularly aspects of cognitive control, which is one of the primary hypothesized functions of the frontoparietal network (FPN). The clinical features of psychotic disorders are known to differ between men and women, but little work has systematically studied neurobiological differences between the sexes, particularly in FEP. The current study aimed to examine sexual dimorphisms in structural integrity of the frontoparietal network (FPN) and its role in cognitive control in FEP.Participants and Methods:A total of 111 FEP patients (68 male, 43 female) and 55 healthy control participants (35 male, 20 female) from the Human Connectome Project for Early Psychosis underwent T1-weighted magnetic resonance imaging and neuropsychological testing were included in the study. Regions of interest (ROIs) included: left and right superior frontal gyrus, left and right middle frontal gyrus, left inferior frontal gyrus, left and right inferior parietal gyrus, right caudate and left thalamus. Using high-dimensional brain mapping procedures, surface shape of the caudate and thalamus was characterized using Large Deformation Diffeomorphic Metric Mapping, and cortical thickness of frontal and parietal regions was estimated using the FreeSurfer toolkit. Cognitive control was assessed using the Fluid Cognition Composite score from the NIH Toolbox Cognition Battery. Multivariate ANOVA models tested group differences, separated by sex, in cortical thickness ROIs, in addition to a whole-brain vertex-wise analysis. Vertex-wise statistical surface t-maps evaluated differences in subcortical surface shape, and Pearson correlations tested relationships between brain regions and Fluid Cognition performance.Results:Results of deep brain region comparisons between schizophrenia males (SCZM) and schizophrenia females (SCZF) groups revealed significant outward deformation at the tail of the right caudate and significant inward deformation along the dorsal aspects of the right caudate. Additionally, significant inward deformation in multiple nuclei of the left thalamus were revealed. Significant negative relationships between Fluid Cognition and the left superior/middle frontal gyrus (r = -0.24, p = 0.05) in the male FEP group were observed. Additionally, significant positive relationships between Fluid Cognition and left inferior frontal gyrus (r = 0.35, p = 0.02) and left inferior parietal gyrus (r = 0.35, p = 0.02) in the female FEP group were found.Conclusions:Overall, findings revealed significant brain differences of the FPN in deep-brain structures only, including abnormal caudal and thalamic shape, in male FEP compared to female FEP, providing evidence of the importance to examine sex differences in deep-brain regions at the first episode. Differential brain relationships with cognitive control also highlight sex-specific presentations that may aid in clinical management and further characterization of the illness in early stages.

Delusional beliefs in adolescents with anorexia nervosa, obsessive-compulsive disorder, or first-episode psychosis: A comparative study

Delusional thinking is a key symptom of first-episode psychosis (FEP), but it has also been studied in obsessive-compulsive disorder (OCD) and anorexia nervosa (AN). This study aimed to analyze the psychometric properties of the Brown Assessment of Beliefs Scale (BABS) in a sample of adolescents diagnosed with a FEP, AN, or OCD, and to compare delusional thinking among the three samples. The sample comprised 60 patients in three groups of 20 diagnosed with OCD, AN, or FEP. Participants underwent assessment by diagnostic interview, the BABS scale, and a measure of depressive symptomatology. Specific instruments were also used to assess the main symptomatology of each disorder. The BABS had good internal consistency, and high validity and reliability. The OCD group scored significantly lower than the other two groups in all scale items except for items 4 (fixation of ideas), 6 (insight), and 7 (delusions of reference). A significant difference only existed between the AN and FEP groups for item 7 (delusions of reference). The BABS scale is a valid and reliable tool for assessing delusionality in adolescents diagnosed with OCD, AN, or FEP, with evidence of marked differences between the disorders. Assessing these symptoms could influence management, helping to improve treatment adherence and prognosis.

Violence in first-episode psychosis: evidence from an early intervention in psychosis programme.

Psychotic disorders are frequently associated with a public perception of dangerousness and belligerence. This situation has contributed to the social stigmatisation of people with severe mental illness and the resulting discrimination that this scenario entails. Despite efforts to demystify such disorders, the association between violent behaviour and psychosis remains unclear. To explore the incidence of the main types of violent offences in a cohort of patients presenting with first-episode psychosis (FEP). Participants were recruited from the First Episode Psychosis Intervention Program (CRUPEP) cohort between 2009 and 2016. The main clinical variables were collected, including medical-forensic records of participants registered at the Basque Institute of Forensic Medicine (BIFM), to identify any violent acts in which participants were involved, either as victims or as offenders. Overall, 79.5% (n = 182) of the participants had no record of violent crime or offence recorded in the BIFM. Annual crime rates for the 2009-2016 period show a decreasing trend in both the general population (IRR = 0.981, 95% CI 0.978-0.983, P < 0.001) and in the FEP group (IRR = 0.019, 95% CI 0.012-0.028, P < 0.001); this pattern is more pronounced in the FEP group. Victimisation accounted for the vast majority of reported incidents; nevertheless, participants who had committed violent offences were mostly involved in intrafamily violence. Individuals with FEP were not involved in a higher number of crimes than the general population. The types of violent acts committed by people with FEP were heterogeneous, with extreme violence being particularly uncommon.

Personality functioning and self-disorders in individuals at ultra-high risk for psychosis, with first-episode psychosis and with borderline personality disorder.

Assessment of personality functioning in different stages of psychotic disorders could provide valuable information on psychopathology, course of illness and treatment planning, but empirical data are sparse. To investigate personality functioning and sense of self in individuals at ultra-high risk (UHR) for psychosis and with first-episode psychosis (FEP) in comparison with a clinical control group of individuals with borderline personality disorder (BPD) and healthy controls. In a cross-sectional design, we investigated personality functioning (Structured Interview of Personality Organization, STIPO; Level of Personality Functioning Scale, LPFS) and disturbances of the basic self (Examination of Anomalous Self-Experience, EASE) in 107 participants, comprising 24 individuals at UHR, 29 individuals with FEP, 27 individuals with BPD and 27 healthy controls. The UHR, FEP and BPD groups had moderate to severe deficits in personality organisation (STIPO) compared with the healthy control group. Self-functioning with its subdomain (facet) 'self-direction' (LPFS) was significantly worse in participants with manifest psychosis (FEP) compared with those at-risk for psychosis (UHR). The FEP group showed significantly worse overall personality functioning than the UHR group and significantly higher levels of self-disturbance (EASE) than the BPD group, with the UHR group lying between these diagnostic groups. Hierarchical cluster analysis based on the seven STIPO domains yielded three clusters differing in level of personality functioning and self-disturbances. Our data demonstrate that psychotic disorders are associated with impaired personality functioning and self-disturbances. Assessment of personality functioning can inform treatment planning for patients at different stages of psychotic disorder.

Suicide risk among individuals at Ultra-High Risk (UHR) of psychosis in a developing North African country: A 12-month naturalistic prospective cohort study from the TRIP project

BackgroundThe limited studies that focused on suicidality in individuals at Ultra-High Risk (UHR) of psychosis were predominantly cross-sectional, emerging from Western countries. We aimed to examine suicide risk among Tunisian UHR and First Episode Psychosis (FEP) patients at baseline, and to evaluate the evolution and correlates of suicidal ideation over a 12-month period in the UHR group exclusively. Methods35 UHR (aged 22.8 ± 4.0 years, 45.7% male) and 33 FEP (aged 27.3 ± 4.8 years, 63.6% male) participants were included. The Comprehensive Assessment of at Risk Mental States, the Positive and Negative Syndrome Scale (PANSS), The Rosenberg Self-Esteem Scale, and The Multidimensional Scale of Perceived Social Support were used. ResultsNo significant differences were found between the UHR and the FEP groups with regard to levels of suicidal ideation at baseline. Suicidal ideation scores showed a significant decrease over time in UHR participants (p=.014; η2=0.242). An increase in total PANSS scores at 1 year (Beta=0.03; p=.048; 95%CI 0.001, 0.060; η2=0.182) significantly increased suicidal ideation scores at 1 year in the UHR group. ConclusionOur findings contribute to the limited body of evidence on this topic by providing new prospective data from a population, country and region that has never been researched previously.

Associations between age and neurocognition in individuals at clinical high risk and first-episode psychosis

Neurocognitive deficits differ with age during the early stages of psychosis. This study aimed to explore age-related differences (9–35 years old) in the neurocognitive performance of a large clinical population. In total, 1059 individuals with first-episode psychosis (FEP), 794 individuals with a clinical high risk of psychosis (CHR), and 774 well-matched healthy controls (HC) were recruited between 2016 and 2021. Neurocognitive assessments were performed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery(MCCB). The MCCB subtest scores differed significantly among the groups across the age span. The mean scores of subtests in CHR individuals were approximately one standard deviation(SD) lower than that of HC, while that of FEP patients was approximately two SDs. The adolescents performed better than the adults in the HC, CHR, and FEP groups. In the HC group, a stronger correlation was found between age and cognitive function, and more neurocognitive domains were affected by age than in the CHR and FEP groups. These results emphasize that neurocognitive deficits in psychosis are present at the pre-onset stage and deteriorate at the first-episode stage across the age span, implicating the development of specific strategies that could monitor the cognitive trajectory in early psychosis.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.