First-episode Psychosis Sample Research Articles

Studying the relationship between intelligence quotient and schizophrenia polygenic scores in a family design with first-episode psychosis population.

The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question. To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample. The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components. FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ. PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients' lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

Medication Adherence in a Transdiagnostic First-Episode Psychosis Sample.

Medication Adherence in a Transdiagnostic First-Episode Psychosis Sample.

Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.

Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries.

The convergent validity of the childhood trauma questionnaire (short-form) and the brief betrayal trauma survey in a first-episode psychosis sample

The convergent validity of the childhood trauma questionnaire (short-form) and the brief betrayal trauma survey in a first-episode psychosis sample

COMT but Not 5HTTLPR Gene Is Associated with Depression in First-Episode Psychosis: The Role of Stressful Life Events.

Serotonergic and dopaminergic systems are involved in the regulation of mood and reactivity to psychological stress. This study explores, in a sample of first episode psychosis (FEP) patients, whether more severe depressive symptoms were found in those who: (1) experienced a major stressful event in the 6 months preceding illness onset; and (2) were homozygous for the COMT Val158 allele or carrying the S allele of 5-HTTLPR. A total of 186 FEP patients recruited were assessed using the Hamilton Rating Scale for Depression (HAMD) for depressive symptoms. Stressful life events (SLEs) were collected by the List of Events Scale. The genotypes of 5-HTTLPR, rs25531, and COMT Val158 Met were performed. It has been found that higher levels of depression is associated with the presence of SLEs (p = 0.019) and with COMT Val158 allele homozygosity (p = 0.029), but not with carrying the S allele of 5-HTTLPR. The COMT gene moderates the association between depression and SLEs as Val158 allele homozygote patients experiencing SLEs had the highest level of depressive symptoms compared to the others (p = 0.002). The present study provides initial evidence for an effect of the COMT Val158 homozygosity and severe stressful life events on the severity of depressive symptoms in first episode psychosis.

Hierarchical Symptom Components in Early Psychosis.

Quantitative models of psychopathology can empirically guide subclassification of heterogeneous clinical presentations such as psychosis; they are particularly well-equipped to capture the nuanced symptomatology observed in first-episode psychosis. As well, components may be better aligned with biological variables. The current study sought to confirm and extend knowledge of the hierarchical structure of psychosis symptoms in first-episode psychosis. Based on past hierarchical work, we hypothesized that a 4 component level would be most closely associated with longitudinal disability. Participants with early-stage psychosis (N = 370) underwent clinical assessment with the scale for the assessment of positive symptoms (SAPS), scale for assessment of negative symptoms (SANS), and global assessment scale(GAS). A subset was assessed at 6 months (N = 221) and 1 year (N = 207). Hierarchical symptom components were extracted at 12 levels. The predictive utility of the components for global functioning was tested. As predicted, the 4-component model (reality distortion, thought disorder, inexpressivity, apathy/asociality) provided a superior prediction of functioning over other levels of the hierarchy. Baseline apathy/asociality longitudinally predicted functioning beyond the shared variance of the components at 6 months (b = -4.83, t(216) = -5.37, p < .001, R2adj = 0.12) and 1-year (b = -4.49, t(202) = -4.38, p < .001, R2adj = 0.09). The hierarchical structure of psychotic symptomatology and its external validity have been robustly established in independent, longitudinal first-episode psychosis samples. The established model incorporates multiple levels of granularity that can be flexibly applied based on the level that offers the greatest predictive utility for external validators.

Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val158Met polymorphism in first episode psychosis

IntroductionCore dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of COMT Val158Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val158Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode. MethodsThe effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9–35 years), sex, ethnicity, handedness and COMT Val158Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample. ResultsCOMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients. ConclusionsOur findings suggest that COMT Val158Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients.

Psychometric properties of the Mindful Attention Awareness Scale (MAAS) in a first-episode psychosis sample.

Despite the considerable growth in mindfulness-based research in the field of psychosis, few attempts have been made to validate mindfulness instruments in this population. This study aimed to evaluate the factorial structure, internal consistency, construct validity, and longitudinal measurement invariance of the Mindful Attention Awareness Scale (MAAS) in a sample of individuals with first-episode psychosis (FEP). In a sample of 150 individuals with remitted FEP, the present study explored the factor structure, measurement invariance, reliability, convergent and discriminant validity of the MAAS. Confirmatory factor analysis supported a single-factor solution, which showed temporal stability, excellent internal consistency reliability (Cronbach's α = .92; McDonald's ω = .93), and theoretically coherent convergent and discriminant validity with measures of well-being, satisfaction with life, savoring, self-compassion, depression, anxiety, stress, and positive symptoms. Overall, the psychometric properties of the MAAS were similar to those described in previous validation studies, thus supporting the value of this instrument to assess the dimension of attention and awareness to the present moment in individuals with FEP. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impact of traumatic life events on clinical variables of individuals with first-episode psychosis and healthy controls.

Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP). To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age. Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered. We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes. The number and cumulative TLEs should be taken into account in the detection, epidemiology and process of recovery in FEP.

Sex-Specific Effect of Serum Lipids and Body Mass Index on Psychotic Symptoms, a Cross-Sectional Study of First-Episode Psychosis Patients.

Background: Schizophrenia is a disorder with considerable heterogeneity in course and outcomes, which is in part related to the patients' sex. Studies report a link between serum lipids, body mass index (BMI), and therapeutic response. However, the role of sex in these relationships is poorly understood. In a cross-sectional sample of first-episode psychosis (FEP) patients, we investigated if the relationship between serum lipid levels (total cholesterol, HDL-C, LDL-C, and triglycerides), BMI, and symptoms differs between the sexes.Methods: We included 435 FEP patients (males: N = 283, 65%) from the ongoing Thematically Organized Psychosis (TOP) study. Data on clinical status, antipsychotics, lifestyle, serum lipid levels, and BMI were obtained. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to assess psychotic and depressive symptoms. General linear models were employed to examine the relationship between metabolic variables and symptomatology.Results: We observed a female-specific association between serum HDL-C levels and negative symptoms (B = −2.24, p = 0.03) and between triglycerides levels (B = 1.48, p = 0.04) and BMI (B = 0.27, p = 0.001) with depressive symptoms. When controlling for BMI, only the association between serum HDL-C levels and negative symptoms remained significant. Moreover, the HDL-C and BMI associations remained significant after controlling for demography, lifestyle, and illness-related factors.Conclusion: We found a relationship between metabolic factors and psychiatric symptoms in FEP patients that was sex-dependent.

Are There Gender Differences in Social Cognition in First-Episode Psychosis?

The aim of this study was to explore gender differences in social cognition in a sample of first-episode psychosis (FEP). An observational descriptive study was performed with 191 individuals with FEP. Emotion perception was assessed using the Faces Test, theory of mind was assessed using the Hinting Task, and attributional style was assessed using the Internal, Personal and Situational Attributions Questionnaire. No gender differences were found in any of the social cognitive domains. Our results suggest that men and women with FEP achieve similar performances in social cognition. Therefore, targeting specific needs in social cognition regarding gender may not be required in early interventions for psychosis.

Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Videogame Play and Wellbeing Among a First Episode Psychosis Population

With ongoing interest in the relationship between videogame and mental health alongside recent focus on gaming's role in coping with stressful life events, we sought to explore the relationship between videogame play and wellbeing among people experiencing their first episode of psychosis. Specifically, we aimed to explore the associations between videogame play and wellbeing among consumers of a first episode psychosis (FEP) service and further to compare their motivations for play, need satisfaction, passion for play and wellbeing to a control group. A sample of 88 people experiencing FEP (57 who played videogames and 31 who did not) and a control sample of 46 (all of whom played videogames) completed a survey containing a range of questionnaires related to the variables of interest. Key findings include that among those experiencing FEP, people who played videogames reported better wellbeing outcomes than those who did not. Among participants who played videogames, the FEP sample reported lower levels of need satisfaction through gaming, lower levels of harmonious passion, higher levels of external types of motivation and lower levels of internal types of motivation for play than the control group. Finally, the relationships between passion orientation (both harmonious and obsessive) and psychological distress were stronger in the control group than the FEP sample, suggesting that passion for gaming may be less influential on wellbeing for those experiencing FEP.

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort.

Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups. The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning. CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

A-8 Developmental Cognitive Phenotypes in First-Episode Psychosis and Longitudinal Cognitive Change Following Antipsychotic Treatment

Abstract Objective The present study applied a developmentally based subgrouping procedure previously examined in chronic psychosis patients to a sample of first-episode psychosis (FEP) and examined change in cognition following treatment with antipsychotic medication. Method Medication naïve FEP patients (n = 119; age = 27.96; 63.9% male; 62.2% White, 32.8% Black, 5.0% Other) recruited during initial hospitalization were categorized into groups based on 1) estimated premorbid intellectual ability and 2) the discrepancy between predicted (modeled on 151 healthy controls) and current cognitive ability. Consistent with findings from chronic psychosis samples, groups were characterized as Preserved (n = 46; average premorbid, no discrepancy), Deteriorated (n = 44; average premorbid, significant discrepancy), and Compromised (n = 29, low premorbid and current cognitive ability). A mixed analysis of variance was used to examine change in a composite cognitive score derived from a comprehensive neuropsychological battery at baseline, 6 weeks, and 12 months. Results There was a significant group by time interaction [Figure 1; F(5.4142.4) = 2.81, p = 0.02] in which the Preserved group performed similar to healthy controls across all time points, the Compromised group demonstrated stable deficits after treatment, and the Deteriorated group diverged from the Compromised group at 6 weeks and 12 months. Discussion There is considerable cognitive heterogeneity in FEP at baseline and after initiation of antipsychotic medication. Findings of cognitive improvement in the Deteriorated group after treatment initiation suggests a differential response to antipsychotic medications that was not found in the Compromised or Preserved groups. Future work may benefit from examining medication and symptom severity as potential factors contributing to the unique change observed in the Deteriorated group.

Stability of schizophrenia diagnosis in a 10-year longitudinal study on first episode of non-affective psychosis: Conclusions from the PAFIP cohort.

To evaluate the 10-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. Changes in diagnosis of 209 FEP patients were described during 10years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves. Out of the 209 patients, 126 were diagnosed of schizophrenia 6months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126schizophrenia patients had changed to a different diagnosis after 10years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow-up. Retrospectively, out of the 154 patients with schizophrenia in the 10-year assessment, 36had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10years.

Genome-wide association study accounting for anticholinergic burden to examine cognitive dysfunction in psychotic disorders.

Identifying genetic contributors to cognitive impairments in psychosis-spectrum disorders can advance understanding of disease pathophysiology. Although CNS medications are known to affect cognitive performance, they are often not accounted for in genetic association studies. In this study, we performed a genome-wide association study (GWAS) of global cognitive performance, measured as composite z-scores from the Brief Assessment of Cognition in Schizophrenia (BACS), in persons with psychotic disorders and controls (N = 817; 682 cases and 135 controls) from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Analyses accounting for anticholinergic exposures from both psychiatric and non-psychiatric medications revealed five significantly associated variants located at the chromosome 3p21.1 locus, with the top SNP rs1076425 in the inter-alpha-trypsin inhibitor heavy chain 1 (ITIH1) gene (P = 3.25×E-9). The inclusion of anticholinergic burden improved association models (P < 0.001) and the number of significant SNPs identified. The effect sizes and direction of effect of the top variants remained consistent when investigating findings within individuals receiving specific antipsychotic drugs and after accounting for antipsychotic dose. These associations were replicated in a separate study sample of untreated first-episode psychosis. The chromosome 3p21.1 locus was previously reported to have association with the risk for psychotic disorders and cognitive performance in healthy individuals. Our findings suggest that this region may be a psychosis risk locus that is associated with cognitive mechanisms. Our data highlight the general point that the inclusion of medication exposure information may improve the detection of gene-cognition associations in psychiatric genetic research.

Reinforcement learning abnormalities in the attenuated psychosis syndrome and first episode psychosis

Prior studies indicate that chronic schizophrenia (SZ) is associated with a specific profile of reinforcement learning abnormalities. These impairments are characterized by: 1) reductions in learning rate, and 2) impaired Go learning and intact NoGo learning. Furthermore, each of these deficits are associated with greater severity of negative symptoms, consistent with theoretical perspectives positing that avolition and anhedonia are associated with impaired value representation. However, it is unclear whether these deficits extend to earlier phases of psychotic illness and when individuals are unmedicated. Two studies were conducted to examine reinforcement learning deficits in earlier phases of psychosis and in high risk patients. In study 1, participants included 35 participants with first episode psychosis (FEP) with limited antipsychotic medication exposure and 25 healthy controls (HC). Study 2 included 17 antipsychotic naïve individuals who were at clinical high-risk for psychosis (CHR) (i.e., attenuated psychosis syndrome) and 18 matched healthy controls (HC). In both studies, participants completed the Temporal Utility Integration Task, a measure of probabilistic reinforcement learning that contained Go and NoGo learning blocks. FEP displayed impaired Go and NoGo learning. In contrast, CHR did not display impairments in Go or NoGo learning. Impaired Go learning was not significantly associated with clinical outcomes in the CHR or FEP samples. Findings provide new evidence for areas of spared and impaired reinforcement learning in early phases of psychosis.

Investigation of the glucocorticoid receptor co-chaperone FKBP5 in individuals with first-episode psychosis

IntroductionStress has been associated with the onset and progression of neuropsychiatric conditions. The neuroendocrine response to psychosocial stressors is mediated via the hypothalamus-pituitary-adrenal axis, resulting in systemic glucocorticoid secretion. FKBP5 is a co-chaperone of the cortisol-bound glucocorticoid receptor. FKBP5 Single Nucleotide Polymorphisms (SNPs) may indicate stress-response alterations, thus affecting vulnerability or resilience to neuropsychiatric phenotypes.ObjectivesTo investigate the FKBP5 polymorphism rs1360780 and FKBP5 mRNA levels in a well-characterized, drug-naïve sample of First-Episode Psychosis (FEP) individuals and matched controls.MethodsFor genotyping rs1360780, whole blood DNA was extracted from FEP individuals and matched controls. The presence of the C (protective)→T (risk) alleles was assessed using TaqMan SNP genotyping assay. Peripheral Blood Mononuclear Cells (PBMCs) were isolated and whole RNA was extracted. FKBP5 mRNA levels were detected with RT-qPCR, using SYBRgreen. Results were normalized against the 18s rRNA reference gene. Statistical analysis was performed in GraphPad Prism 8.ResultsThe distribution of C→T alleles of rs1360780 genotyped in FEP (N=44) and controls (N=39) indicate a statistically significant prevalence of the C/C alleles in FEP individuals (*p=0.0432). mRNA FKBP5 data revealed increased levels of FKBP5 in FEP individuals (N=25) compared to controls (N=18), (***p=0.0007).ConclusionsOur data show increased FKBP5 mRNA levels in FEP individuals compared to matched controls, as well as the presence of the rs1360780 protective (C) allele. Follow up studies include investigation of the translational profile of stress-mediators, in order to pave an individualized approach towards deciphering psychosis onset pathobiology.DisclosureNo significant relationships.