Functioning In First-episode Psychosis Research Articles

Identify Potential Causal Relationships Between Cortical Thickness, Mismatch Negativity, Neurocognition, and Psychosocial Functioning in Drug-Naïve First-Episode Psychosis Patients.

Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP. We enrolled 28 drug-naïve FEP and 34 age and sex-matched healthy controls. Clinical symptoms, neurocognition, psychosocial functioning, auditory duration MMN, and T1 structural magnetic resonance imaging data were collected. We measured CT in the superior temporal gyrus (STG), a primary MMN-generating region. We found a significant negative correlation between MMN amplitude and bilateral CT of STG (CT_STG) in FEP (left: r = -.709, P < .001; right: r = -.612, P = .008). Multiple mediation models revealed that a thinner left STG cortex affected functioning through both direct (24.66%) and indirect effects (75.34%). In contrast, the effects of the right CT_STG on functioning were mainly mediated through MMN and neurocognitive pathways. Bilateral CT_STG showed significant association with MMN, and MMN plays a mediating role between CT and cognition. Both MMN alone and its interaction with cognition mediated the effects of structural alterations on psychosocial function. The decline in overall function in FEP may stem from decreased CT_STG, leading to subsequent MMN deficits and neurocognitive dysfunction. These findings underline the crucial role of MMN in elucidating how subtle structural alterations can impact neurocognition and psychosocial function in FEP.

The role of cognitive reserve and clinical symptoms in the association between genetic liability for educational attainment and functioning in first-episode psychosis: a mediation analysis.

The role of cognitive reserve and clinical symptoms in the association between genetic liability for educational attainment and functioning in first-episode psychosis: a mediation analysis.

Cannabis Use and Endocannabinoid Receptor Genes: A Pilot Study on Their Interaction on Brain Activity in First-Episode Psychosis.

The role of both cannabis use and genetic background has been shown in the risk for psychosis. However, the effect of the interplay between cannabis and variability at the endocannabinoid receptor genes on the neurobiological underpinnings of psychosis remains inconclusive. Through a case-only design, including patients with a first-episode of psychosis (n = 40) classified as cannabis users (50%) and non-users (50%), we aimed to evaluate the interaction between cannabis use and common genetic variants at the endocannabinoid receptor genes on brain activity. Genetic variability was assessed by genotyping two Single Nucleotide Polymorphisms (SNP) at the cannabinoid receptor type 1 gene (CNR1; rs1049353) and cannabinoid receptor type 2 gene (CNR2; rs2501431). Functional Magnetic Resonance Imaging (fMRI) data were obtained while performing the n-back task. Gene × cannabis interaction models evidenced a combined effect of CNR1 and CNR2 genotypes and cannabis use on brain activity in different brain areas, such as the caudate nucleus, the cingulate cortex and the orbitofrontal cortex. These findings suggest a joint role of cannabis use and cannabinoid receptor genetic background on brain function in first-episode psychosis, possibly through the impact on brain areas relevant to the reward circuit.

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: a network analysis from the OPTiMiSE trial

IntroductionNetwork analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains.ObjectivesThe current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.MethodsBaseline data from the OPTiMiSE trial were analysed. The sample included 446 participants (age 40.0±10.9 years, 70% males). The network was estimated with a Gaussian graphical model (GGM), using scores on individual items of the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network (Fig. 1). The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganisation, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.Image:ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.Disclosure of InterestNone Declared

Autistic features and executive functions in first episode psychosis: Associations with functionality and quality of life.

The present study aimed at investigating the relationships between autistic features and cognitive deficits, functionality and quality of life in first episode psychosis (FEP) patients. Sixty FEP patients [mean age (SD)=32.53 (10.74), n=23 female, n=37 male] were enrolled in this cross-sectional study. Data was collected using a sociodemographic and clinical data form, the Positive and Negative Syndrome Scale (PANSS), the PANSS Autism Severity Score (PAUSS), the Personal and Social Performance Scale (PSP), the Frontal Assessment Battery (FAB), and the World Health Organization Quality of Life Scale Short Form in Turkish Version (WHOQOL-BREF TR). Autistic symptom severity was found to be higher in males than females, and higher in patients with a family history of psychotic disorder. An inverse relationship was found between the duration of education and the severity of autistic symptoms. While there was an inverse relationship between autistic symptom severity and executive functions and functionality, no significant correlation was found with quality of life. Negative symptom severity was a predictor of executive functions and functionality. No significant difference was observed between autistic and psychotic domains which were related to executive functions. Our study is the first to examine the relationship between autistic/psychotic symptoms and executive functions and functionality in patients with FEP. The results show that autistic symptoms are associated with worse social and personal functioning and worse executive functions in patients with FEP. Longitudinal follow-up studies with larger samples are required to determine the direction of the relations.

Association between Symptom Dimensions and Psychosis Risk Factors with Functioning in First Episode Psychosis: A Six Months Prospective Study

Association between Symptom Dimensions and Psychosis Risk Factors with Functioning in First Episode Psychosis: A Six Months Prospective Study

Is Metacognitive Training effective for improving neurocognitive function in patients with a recent onset of psychosis?

The aims are to assess improvements in memory, attention and executive function in first-episode psychosis after Metacognitive Training (MCT). A multicenter randomized clinical trial was performed with two arms: MCT and psychoeducational intervention. A total of 126 patients with a diagnosis of psychosis, less than 5 years from the onset of the disease, were included. Patients were assessed two or three moments (baseline, post-treatment, 6 months follow-up) depending on the test, with a battery of neurocognitive tests (TAVEC, TMTA-B, CPT, WCST, Stroop and premorbid IQ). General linear models for repeated measures were performed. A better improvement in the MCT was found by an interaction between group and time in CPT Hit index, TMTB, Stroop, recent memory and number of perseverations of the TAVEC. Considering three assessments, a better improvement was found in non-perseverative, perseverative and total errors of the WCST and TMTB. The MCT is an effective psychological intervention to improve several cognitive functions.

The Relationship between Cognitive Functions and Psychopathological Symptoms in First Episode Psychosis and Chronic Schizophrenia.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial.

Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes. Baseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0±10.9years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes. Nodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value. The current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.

P.0157 Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the athens first-episode psychosis research study

P.0157 Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the athens first-episode psychosis research study

Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study.

Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal and cross-sectional associations of a weighted score of cumulative environmental liability for schizophrenia - the exposome score for schizophrenia (ES-SCZ) - with functioning in first-episode psychosis (FEP). Data were derived from the baseline and 1-month assessments of the Athens FEP Research Study that enrolled 225 individuals with FEP. The Global Assessment of Functioning (GAF) and the Personal and Social Performance Scale (PSP) were used to measure social, occupational, and psychological functioning. The ES-SCZ was calculated based on the previously validated method. ES-SCZ was associated with the total scores of GAF and PSP at baseline and 1-month assessments. These findings remained significant when accounting for several associated alternative explanatory variables, including other environmental factors (obstetric complications, migration, ethnic minority), clinical characteristics (duration of untreated psychosis, symptom severity, previous antipsychotic use), and family history of psychosis, demonstrating that the association between ES-SCZ and functioning is over and above other risk factors and cannot be explained by symptom severity alone. Functioning improved from baseline to 1-month assessment, but no significant ES-SCZ-by-time interaction was found on functioning, indicating that functioning changes were not contingent on ES-SCZ. Our findings suggest that rather than a predictor of functional improvement, ES-SCZ represents a stable severity indicator that captures poor functioning in early psychosis. Environmental risk loading for schizophrenia (ES-SCZ) can be beneficial for clinical characterization and incorporated into transdiagnostic staging models.

Relationship of subjective quality of life with symptomatology, neurocognition and psychosocial functioning in first-episode psychosis: a structural equation modelling approach.

Subjective quality of life (SQoL) represents an important outcome of psychotic disorders. However, determinants of SQoL and their complex inter-relationships in the early course of illness remain to be clarified. Association between neurocognitive impairment and SQoL in first-episode psychosis (FEP) is understudied. This study employed structural equation modeling (SEM) to examine relationships among SQoL, depressive, positive and negative symptoms, neurocognition, and psychosocial functioning in FEP patients. Three hundred and forty-seven patients aged 25-55years presenting with FEP to early intervention program in Hong Kong were recruited. Assessment encompassing symptom profiles, psychosocial functioning and a battery of neurocognitive tests were conducted. SF-12 mental component summary scores were computed as the primary measure of SQoL. Our correlation analyses revealed differential relationships between negative symptom subdomains and SQoL, with amotivation, but not diminished expression, being related to SQoL. Final SEM model yielded a good model fit (comparative fix index = 0.94; root mean square error of approximation = 0.05; standardized root mean square residuals = 0.07) and demonstrated that depression, positive symptoms and psychosocial functioning were directly associated with SQoL, with depression showing the strongest effect. Amotivation, neurocognition and positive symptoms had an indirect effect on SQoL via the mediation of psychosocial functioning. This study affirms depression as a critical determinant of subjective mental wellbeing, and underscores an intermediary role of psychosocial functioning in linking amotivation, neurocognitive impairment and positive symptoms to SQoL in FEP patients. Depression and functional impairment thus constitute as crucial therapeutic targets for improvement of SQoL in the early illness stage.

Towards Clinically Relevant Oculomotor Biomarkers in Early Schizophrenia.

In recent years, psychiatric research has focused on the evaluation and implementation of biomarkers in the clinical praxis. Oculomotor function deviances are among the most consistent and replicable cognitive deficits in schizophrenia and have been suggested as viable candidates for biomarkers. In this narrative review, we focus on oculomotor function in first-episode psychosis, recent onset schizophrenia as well as individuals at high risk for developing psychosis. We critically discuss the evidence for the possible utilization of oculomotor function measures as diagnostic, susceptibility, predictive, monitoring, and prognostic biomarkers for these conditions. Based on the current state of research we conclude that there are not sufficient data to unequivocally support the use of oculomotor function measures as biomarkers in schizophrenia.

Relationships Between Sensory Gating, Cognition, Clinical Symptoms and Real-Life Functioning in First Episode Psychosis

Relationships Between Sensory Gating, Cognition, Clinical Symptoms and Real-Life Functioning in First Episode Psychosis

The effect of family environment and psychiatric family history on psychosocial functioning in first-episode psychosis at baseline and after 2 years

The aim of the present study was to evaluate the contribution of family environment styles and psychiatric family history on functioning of patients presenting first-episode psychosis (FEP). Patients with FEP and healthy controls (HC) were assessed at baseline and after 2 years. The Functional Assessment Short Test (FAST) was used to assess functional outcome and the Family Environment Scale (FES) to evaluate family environment. Linear regressions evaluated the effect that family environment exerts on functioning at baseline and at 2-year follow-up, when FEP patients were diagnosed according to non-affective (NA-PSYCH) or affective psychoses (A-PSYCH). The influence of a positive parents’ psychiatric history on functioning was evaluated through one-way between-groups analysis of covariance (ANCOVA) models, after controlling for family environmental styles. At baseline, FEP patients presented moderate functioning impairment, significantly worse than HC (28.65±16.17 versus 3.25±7.92; p<0.001, g = 1.91). At 2-year follow-up, the functioning of NA-PSYCH patients was significantly worse than in A-PSYCH (19.92±14.83 versus 12.46±14.86; p = 0.020, g = 0.50). No specific family environment style was associated with functioning in FEP patients and HC. On the contrary, a positive psychiatric father's history influenced functioning of FEP patients. After 2 years, worse functioning in NA-PSYCH patients was associated with lower rates of active-recreational and achievement orientated family environment and with higher rates of moral-religious emphasis and control. In A-PSYCH, worse functioning was associated with higher rates of conflict in the family. Both family environment and psychiatric history influence psychosocial functioning, with important implications for early interventions, that should involve both patients and caregivers.

Cognitive functioning in first episode psychosis. Gender differences and relation with clinical variables.

to study the differences in cognitive functioning in patients and controls. In addition, study the influence of symptoms, cannabis consumption, chlorpromazine doses, DUP and IQ in cognitive performance in patients, both in the total sample and divided by gender. 70 first episode psychosis patients and 63 healthy controls (HC) participated in the study and were assessed with the MATRICS battery and the Vocabulary subtest of WAIS-IV. Symptoms in FEP patients were evaluated with the Emsley factors of the PANSS scale. patients showed lower scores than controls in all cognitive domains studied. There were no significant differences between FEP men and FEP women, but we found gender differences in favour of women in processing speed, working memory and composite total scored domains in the HC group. Finally, symptoms and Chlorpromazine doses showed an influence on cognitive performance in the total FEP sample. When splitting the sample by gender, positive symptoms may be more detrimental to women's cognitive functioning, while disorganized symptoms may play the most important role in cognitive performance in men. patients showed worse cognitive performance in all cognitive domains compared to healthy controls. In our FEP sample, gender does not seem to influence cognitive performance measured with the MATRICS. Severity of symptoms influences positively in cognitive performance. The dose of Chlorpromazine and symptoms are influential variables to be taken into account in cognition rehabilitation programs.

P.553 Negative symptoms correlate with social functioning in first-episode psychosis: results from a cross-sectional study

P.553 Negative symptoms correlate with social functioning in first-episode psychosis: results from a cross-sectional study

Anxiety symptoms in first-episode psychosis.

Anxiety disorders and symptoms are common in people with psychotic disorders, having a negative impact on clinical status, function level and overall prognosis. However, research on the significance of anxiety in predicting remission and long-term functioning in first-episode psychosis (FEP) is still scarce. This study investigated the effects of anxiety and obsessive-compulsive symptoms (OCS) on clinical and functional improvement in individuals with FEP. FEP patients (N = 97) aged 18-40 years were recruited from the University Hospital District of Helsinki and the City of Helsinki. Psychotic and anxiety symptoms were measured using the Brief Psychiatric Rating Scale. Obsessive-compulsive symptoms were assessed using the Obsessive-Compulsive Inventory (OCI-R), and functioning was evaluated using the Social and Occupational Functioning Assessment Scale (SOFAS). Follow-up measurements were performed at 2 and 12 months. We specifically studied whether anxiety and obsessive-compulsive symptoms at the 2-month follow-up assessment, at a time when the initial treatment response had been achieved, would predict outcomes at 12 months. Symptoms of anxiety and OCS correlated moderately with each other and psychotic symptoms, but at the 12-month follow-up, OCS no longer correlated significantly with psychotic and anxiety symptoms. When the level of psychotic symptoms was adjusted for, more severe OCS at the 2-month follow-up was associated with a lower rate of remission at 12 months, whereas a higher level of anxiety symptoms at 2 months was associated with better functioning at 12 months. OCS may be predictive of poorer clinical outcomes, whereas anxiety symptoms may predict better functional outcomes.

4327 Structural Neural Correlates of Social Functioning in First Episode Psychosis and Malleability in Response to Targeted Cognitive Training

OBJECTIVES/GOALS: Development of interventions that improve social functioning (SF) in first episode psychosis (FEP) is hindered by a poor understanding of the neural mechanisms underlying SF deficits. This research aims to identify neural correlates of social functioning in FEP, and to evaluate whether this substrate is malleable in response to cognitive training. METHODS/STUDY POPULATION: This is a secondary data-analysis of participants in an ongoing randomized clinical trial investigating whether 12 weeks of targeted cognitive training is neuroprotective in FEP, versus treatment as usual. Baseline and post-training assessments include a brain MRI, three measures of SF, and a neurocognitive battery. Healthy controls complete MRI only. Differences in cortical thickness (CTh) and gray matter volume (GMV) in regions of interest between FEP and controls will be determined with ANCOVA. Multiple linear regression will be used to determine the relationship between neural substrate and SF in FEP. Linear mixed models will be used to examine the relationship between change in CTh and GMV and change in SF. Data collection is ongoing for this study. RESULTS/ANTICIPATED RESULTS: In preliminary data including 12 FEP and 9 healthy controls, FEP demonstrated cortical loss in the right superior frontal cortex and the right isthmus-posterior cingulate. Greater cortical thickness in the posterior cingulate cortex was associated with better social functioning across multiple measures when controlling for global cognition. Gray matter volume in the parahippocampal gyrus was also associated with better social functioning. Preliminary results evaluating whether targeted cognitive training is neuroprotective in these regions of interest in a manner that is associated with improved social functioning will also be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results link the posterior cingulate and parahippocampal gyrus to SF in FEP. Further research will investigate the contribution of changes in these brain regions to improved SF. The identification of biological treatment targets for SF may lead to development and optimization of novel interventions to alleviate SF deficits in FEP.

S166. EFFECTIVE CONNECTIVITY OF FRONTOSTRIATAL SYSTEMS IN FIRST-EPISODE PSYCHOSIS

BackgroundNeuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP).MethodsA total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model.ResultsDCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms.DiscussionAberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down dysregulation of dopamine function in FEP, as dopaminergic activity in the midbrain is proposed to be under the control of higher brain areas. In patients, increased self-inhibition of the midbrain, as well as symptom associations in both ingoing and outgoing connections of this region, are congruous with hyperactivity of the midbrain as proposed by the dopamine dysregulation hypothesis. Here, we demonstrate that mathematical models of brain imaging signals can be used to identify the key disruptions driving brain circuit dysfunction, identifying new targets for treatment.