First-episode Psychosis Individuals Research Articles

M96 - GENOME-WIDE DNA METHYLATION ANALYSIS IN A LONGITUDINAL COHORT OF ANTIPSYCHOTIC-NAIVE FIRST EPISODE OF PSYCHOSIS PATIENTS

Background The study of the early stages of schizophrenia, the First-Episode Psychosis (FEP), is critical given that brain abnormalities and cognitive deficits are already present. Although less investigated than chronic schizophrenia, FEP individuals have a shorter period of medication and duration of symptoms. In this study, we aimed to identify genetic markers, using whole DNA methylation, for psychotic disorder and antipsychotic treatment in blood of a FEP cohort before and after two months of risperidone. Methods Sixty controls and sixty antipsychotic naive FEP patients followed-up for two months after risperidone (FEP-2M) were recruited. All patients were 16–40 years old and have met the criteria of psychotic diagnoses according to DSM-IV. We generated the DNA methylation data using the Human Illumina 450 K BeadChip microarray. We used limma R package, using two separate analyses: FEP x HC and FEPxFEP-2M (paired); and addind sex, age, smoking data and cell type proportion as covariates. We considered as significant Differentially Methylated Positions (DMPs) with p value lower than 0.05 after a Bonferroni correction for multiple comparisons and differentially methylated regions (DMRs) with at least two significant DMPs (FDR) within a 500 bp region. Results We found 5 DMRs and 16 DMPs comparing controls and FEP, and 14 DMRs and 77 DMPs between FEP before and after treatment. Discussion To our knowledge, this is the first study to find DMRs in a longitudinal cohort of antipsychotic naive FEP patients. Collectively, DMRs in the longitudinal comparison seem to be related to the adverse effects and the response to risperidone. Notably, the most associated genomic region in schizophrenia (previously reported by the PGC), the MHC region, is differentially methylated in patients after the treatment, demonstrating an epigenetic modification caused by risperidone in an important schizophrenia genomic region. Identifying the genetic and molecular changes of drug response is one of the first steps through personalized medicine, further studies should replicate these results and aim antipsychotic naive individuals treated with other antipsychotics.

Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study.

The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

Resting-state functional brain networks in first-episode psychosis: A 12-month follow-up study.

Schizophrenia is increasingly conceived as a disorder of brain network connectivity and organization. However, reports of network abnormalities during the early illness stage of psychosis are mixed. This study adopted a data-driven whole-brain approach to investigate functional connectivity and network architecture in a first-episode psychosis cohort relative to healthy controls and whether functional network properties changed abnormally over a 12-month period in first-episode psychosis. Resting-state functional connectivity was performed at two time points. At baseline, 29 first-episode psychosis individuals and 30 healthy controls were assessed, and at 12 months, 14 first-episode psychosis individuals and 20 healthy controls completed follow-up. Whole-brain resting-state functional connectivity networks were mapped for each individual and analyzed using graph theory to investigate whether network abnormalities associated with first-episode psychosis were evident and whether functional network properties changed abnormally over 12 months relative to controls. This study found no evidence of abnormal resting-state functional connectivity or topology in first-episode psychosis individuals relative to healthy controls at baseline or at 12-months follow-up. Furthermore, longitudinal changes in network properties over a 12-month period did not significantly differ between first-episode psychosis individuals and healthy control. Network measures did not significantly correlate with symptomatology, duration of illness or antipsychotic medication. This is the first study to show unaffected resting-state functional connectivity and topology in the early psychosis stage of illness. In light of previous literature, this suggests that a subgroup of first-episode psychosis individuals who have a neurotypical resting-state functional connectivity and topology may exist. Our preliminary longitudinal analyses indicate that there also does not appear to be deterioration in these network properties over a 12-month period. Future research in a larger sample is necessary to confirm our longitudinal findings.

F154. ABERRANT SALIENCE NETWORK FUNCTIONAL CONNECTIVITY IN AUDITORY VERBAL HALLUCINATIONS: A FIRST EPISODE PSYCHOSIS SAMPLE

BackgroundAuditory verbal hallucinations (AVH) often lead to distress and functional disability, and are frequently associated with psychotic illness. Theories of abnormal integration have been proposed to explain symptoms of schizophrenia, including delusions and hallucinations, with a central abnormality being aberrant activity in intrinsic brain networks such as the default mode network (DMN) or the salience network (SN). Previous investigations of patients with schizophrenia assessing functional connectivity (FC) have used a seed-based functional connectivity approach (sb-FC), with seed placement in brain areas responsible for auditory processing, language, and memory; the striatum, and in areas of DMN. These have generated some conflicting results, possibly because of the varying seed placement. The aim of the current study was to address these confounding factors by investigating the intrinsic FC in first episode psychosis (FEP) patients with AVH using within-sample AVH symptom capture seeds. It was hypothesised that patients would show aberrant resting state FC between areas of the DMN and SN and these areas.MethodsEighteen FEP individuals and 20 healthy controls were recruited. All the participants underwent resting-state functional Magnetic Resonance Imaging (rs-fMRI). The Data Processing Assistant for Resting-State fMRI Advanced Edition (DPARSFA) V3.1 (http://rfmri.org/DPARSF) (Yan & Zang, 2010) and the statistical parametric mapping software 8 (SPM8) (SPM, Friston, The Wellcome Department of Cognitive Neurology, London, Uk; http://www.fil.ion.ucl.ac.uk/spm) were used to preprocess and analyze the data.ResultsPatients showed increased FC between left insula and bilateral cerebellum, and angular gyrus; and increased FC between left claustrum and left cerebellum and postcentral gyrus. There was reduced FC in FEP patients with AVH between left claustrum and left insula compared to HC. The FC between left insula and left claustrum seeds for patients and HC is shown separately in supplementary information. There were no significant correlations between DUP, dose of antipsychotic medications, and severity of hallucinations and the mean coefficients of clusters that were significantly different between FEP patients and HC.DiscussionFEP patients showed increased functional connectivity between left insula and bilateral cerebellum and angular gyrus; and increased functional connectivity between left claustrum and left cerebellum and postcentral gyrus. We also found reduced functional connectivity between left claustrum and left insula in FEP patients compared to HC. It is possible the pathology of AVH is primarily located in the insula and angular gyrus. However, given our results of both the left insula seed in patients and HC shows connectivity with right insula and anterior cingulate cortex (key regions of SN) and literature from patients with chronic AVH, the suggestion may be that resting state dysconnectivity within the DMN and SN are implicated in the generation of AVH, which during the experience itself will further involve temporal and auditory networks. Furthermore, decreased intrinsic functional connectivity between the claustrum and the insula may lead to compensatory over activity in parts of the auditory network including areas involved in DMN, auditory processing, language and memory, leading to the complex and individual content of AVH when they occur.

S173. GREY MATTER VOLUME DEFFICITS IN PATIENTS WITH A FIRST EPISODE NON-AFFECTIVE PSYCHOSIS AND SUICIDE RELATED BEHAVIOUR

BackgroundSuicide represents the main cause of premature dead in first episode psychosis (FEP) patients. However, our understanding of suicidal behaviour in this population is limited. During the last decade, several works have related suicidal behaviour in FEP patients with structural abnormalities in frontal and temporal areas as well as specific structures such as hippocampus, insula and amygdala. The main aim of this work was to analyse the possible structural brain abnormalities associated with suicide-related-behaviour in a large sample of FEP patients.MethodsWe use a voxel-based morphometry (VBM) analysis in 146 FEP individuals: 24 FEP with and 122 without suicidal behaviour. All images were taken in the same 3T Phillips scanner. The CAT 12 toolbox, which is implemented in SPM12 was used for VBM analysis of the data. A two-sample t-test was set with sex, age, handedness, total intracraneal volume and global disability score as nuisance covariables. We applied threshold-free cluster enhancement (TFCE) with 5000 permutations and corrected for multiple comparisons (FWE) at p<0.05.ResultsA gradual reduction of grey matter volume related to presence of suicide-related-behaviour was found in frontal area, specifically in superior frontal gyrus, middle frontal gyrus, precentral gyrus, inferior frontal gyrus and orbital gyrus. In addition, significant reduction was found in middle temporal gyrus as well as in posterior cingulate gyrus and precuneus.DiscussionOur results are in line with previous works which related suicidal behaviours with reduced frontal regions. Frontal areas are involved in: i) cognitive analysis; ii) foresight and weighing consequences of behaviour; iii) considering future and making predictions; iv) impulse control; v) delaying gratification; vi) inhibiting inappropriate behaviour; vii) initiating appropriate behaviour. Reestructuraria esta frase asi: On the other hand, precuneus is involved in: i) episode memories; ii) reflective self-awareness; iii) executive function; and iv) it is activated during judgements. Finally, cingulate gyrus has been strongly associated with emotional responses to pain, regulation of aggressive behaviour and decision making. Finally, middle temporal gyrus appears to play an important role in retrieving semantic information.This study provides some insights about brain abnormalities associated with suicide-related-behaviours in FEP patients. In particular, the areas reported in this study are related with important functions such as impulsivity, emotional processing information, responses to pain and aggressiveness which are strongly associated with suicide-related-behaviours. Further studies are necessary to replicate the relevance of these structures in suicidal behaviour in FEP patients.

The effect of excess weight on circulating inflammatory cytokines in drug-na\xefve first-episode psychosis individuals

BackgroundLow-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP).ObjectivesThe aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals.MethodsThis is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI.ResultsIn the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1β, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1β, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls.ConclusionsMost differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.

Character strengths of individuals with first episode psychosis in Individual Resiliency Training

Positive psychology interventions that integrate a person's strengths into treatment result in improvements in life satisfaction and well-being. Character strengths classified within six core virtues (wisdom/knowledge, courage, humanity, justice, temperance, and transcendence) have been the subject of substantial research. Though a number of studies have been conducted in the general population, little is known about the character strengths of individuals with first episode psychosis (FEP). Moreover, positive psychology principles, in particular a focus on personal strengths, have been increasingly integrated into FEP treatment and was a core component of Individual Resiliency Training (IRT), the individual therapy component of NAVIGATE tested in the Recovery After an Initial Schizophrenia Episode Early Treatment Program. As such, the present study offers an examination of character strengths among 105 FEP clients in specialized early intervention treatment. The present study included two primary aims: 1) to conduct a descriptive analysis of character strengths of FEP individuals and 2) to examine exploratory associations between character strengths and changes in symptomatic and recovery variables over six months. Results revealed that the most commonly identified strengths were: Honesty, Authenticity, and Genuineness (40.95%), Kindness and generosity (37.14%), Fairness, equity, and justice (29.52%), Gratitude (29.52%), and Humor and playfulness (29.52%). Three virtues (Humanity, Justice, and Transcendence) were significantly associated with improvements in symptoms, psychological well-being, and interpersonal relations over six months. Overall, the present study offers a glimpse into how persons with FEP view their strengths and how certain clusters of strengths are related to important outcomes.

“With a little help from my friends” social predictors of clinical recovery in first-episode psychosis

Social functioning is a conglomerate of factors central to clinical recovery after a first-episode psychosis. There is a lack of studies investigating the relative impact of factors related to social interaction. Disentangling these could facilitate improvement of psychosocial interventions. This study aims to investigate the impact of social interactions on two-year clinical recovery in first-episode psychosis, by examining frequency and satisfaction of relationships with family and friends. A baseline sample of 178 first-episode psychosis individuals were followed up over two years regarding social functioning and clinical status. We longitudinally compared those who were to those who were not recovered using generalized estimating equations analyses. Our results showed that frequency of social interactions with friends was a significant positive predictor of clinical recovery over a two-year period. Perceived satisfaction with relationships, and frequency of family interaction did not show significant effects. We conclude that interaction with friends is a malleable factor that could be targeted for early intervention. This would facilitate protective factors through the preservation of existing social networks and thus reduce the risk of disability associated with long-term psychosis. Findings indicate that even individuals with an inclination towards social withdrawal and isolation could benefit from this type of intervention.

Identifying neurocognitive markers for outcome prediction of global functioning in individuals with first-episode and ultra-high-risk for psychosis.

There is an increasing need for identifying neurocognitive predictors of global functional outcome in early psychosis toward optimizing an early intervention strategy. We conducted a longitudinal observational study to investigate an association between neurocognitive assessments at baseline and global functional outcome at an average of 1-year follow up. Participants included ultra-high-risk for psychosis (UHR) individuals who had not converted to psychosis during the follow-up period (UHR-NP) and those with first-episode psychosis (FEP). We evaluated neurocognition at baseline using the Brief Assessment of Cognition in Schizophrenia Japanese version, including Verbal Memory, Working Memory, Motor Speed, Verbal Fluency, Attention/Processing Speed, and Executive Function. We also assessed global functional outcome using the modified Global Assessment of Functioning (mGAF) scale both at baseline and after the follow-up period. Thirty-four UHR-NP individuals (34/47, 72%) and 29 FEP individuals (29/36, 81%) completed assessment of neurocognitive function at baseline and functional outcome at follow up. In the UHR-NP group, Attention/Processing Speed was significantly associated with the mGAF score at follow up. In the FEP group, Executive Function was significantly associated with the average mGAF score during follow up. Attention/Processing Speed and Executive Function at baseline may predict global functional outcome of early psychosis. These neurocognitive tests are easy to incorporate in clinical settings and, if replicated in independent samples, may be included in routine clinical assessments for prediction of functional outcome in early psychosis.

Gene-environment interaction as a predictor of early adjustment in first episode psychosis

BackgroundThis study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. MethodsWe constructed a schematic ‘two-hit’ model, with Val/Val homozygosity for the catechol-O-methyltransferase (COMT) Val158Met polymorphism as the ‘first hit’ and history of obstetric complications and parental socioeconomic status as ‘second hits’. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls. ResultsThe interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP individuals and in controls, and remained significant after controlling for age, sex, and diagnosis. ConclusionsIndividuals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.

Modeling the Interplay Between Psychological Processes and Adverse, Stressful Contexts and Experiences in Pathways to Psychosis: An Experience Sampling Study.

Several integrated models of psychosis have implicated adverse, stressful contexts and experiences, and affective and cognitive processes in the onset of psychosis. In these models, the effects of stress are posited to contribute to the development of psychotic experiences via pathways through affective disturbance, cognitive biases, and anomalous experiences. However, attempts to systematically test comprehensive models of these pathways remain sparse. Using the Experience Sampling Method in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls, we investigated how stress, enhanced threat anticipation, and experiences of aberrant salience combine to increase the intensity of psychotic experiences. We fitted multilevel moderated mediation models to investigate indirect effects across these groups. We found that the effects of stress on psychotic experiences were mediated via pathways through affective disturbance in all 3 groups. The effect of stress on psychotic experiences was mediated by threat anticipation in FEP individuals and controls but not in ARMS individuals. There was only weak evidence of mediation via aberrant salience. However, aberrant salience retained a substantial direct effect on psychotic experiences, independently of stress, in all 3 groups. Our findings provide novel insights on the role of affective disturbance and threat anticipation in pathways through which stress impacts on the formation of psychotic experiences across different stages of early psychosis in daily life.

The role of vulnerability factors in individuals with an at-risk mental state of psychosis.

Several indicators of heightened vulnerability to psychosis and relevant stressors have been identified. However, it has rarely been studied prospectively to what extent these vulnerability factors are in fact more frequently present in individuals with an at-risk mental state for psychosis. Moreover, it remains unknown whether any of these contribute to the prediction of psychosis onset in at-risk mental state individuals. There were 28 healthy controls, 86 first-episode psychosis patients and 127 at-risk mental state individuals recruited within the Basel "Früherkennung von Psychosen" project. Relative frequencies of selected vulnerability factors for psychosis were compared between healthy controls, psychosis patients, those at-risk mental state individuals with subsequent psychosis onset (n = 31) and those without subsequent psychosis onset (n = 55). Survival analyses were applied to determine associations between time to transition to psychosis and vulnerability factors in all 127 at-risk mental state individuals. The vulnerability factors/indicators such as "difficulties during school education or vocational training", "difficulties during employment", "being single", "difficulties with intimate relationships" and "being burdened with specific stressful situations" were more commonly found in the at-risk mental state and first-episode psychosis group than in healthy controls. At-risk mental state and first-episode psychosis individuals more frequently present with vulnerability factors. Individual vulnerability factors appear, however, not to be predictive for an onset of psychosis.

Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study.

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ2 = 6.3, P = 0.044), activities (χ2 = 6.7, P = 0.036), and areas (χ2 = 9.4, P = 0.009) and enhanced threat anticipation (χ2 = 9.3, P = 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ2 = 5.7, P = 0.058) and aberrantly salient experiences (χ2 = 12.3, P = 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder.

Antipsychotic Treatment Reduces Indices of Oxidative Stress in First-Episode Psychosis Patients.

38 first-episode psychosis (FEP) patients and 37 control subjects were recruited for the study of indices of oxidative stress (OxS). The main purpose of the study was to compare the OxS statuses (serum total antioxidant capacity (TAC), total level of peroxides (TPX), oxidative stress index (OSI), and ratio oxidized methionine (Met-SO) to methionine (Met)) between antipsychotic-naïve FEP patients and individuals without a history of psychiatric disorders. Subsequently, the impact of 7-month antipsychotic treatment was evaluated on the OxS status in FEP patients. An attempt was made to assess links between OxS signature and inflammation markers. The oxidative stress indices remained generally unchanged in antipsychotic-naïve FEP patients compared to control subjects. Despite that, there was a significant correlation between the levels of TPX and EGF (endothelial growth factor) in FEP patients. This correlation disappeared after antipsychotic treatment of FEP patients. Moreover, antipsychotic treatment was associated with a significant reduction in OxS indices, including TPX, OSI, and ratio between Met-SO and Met. By contrast, in chronic SCZ patients we established a significant high-grade OxS. In conclusion, the markers of total antioxidative capacity, lipid peroxidation, and protein oxidation revealed no high-grade OxS in FEP patients. Nevertheless, antipsychotic treatment induced a considerable anti-inflammatory effect. OxS levels were also significantly decreased if compared in FEP patients before and after antipsychotic treatment.

The relationship between cognition, job complexity, and employment duration in first-episode psychosis.

To investigate the relationship between cognition and employment duration in first-episode psychosis (FEP), and establish if a "fit" between cognition and job complexity is associated with longer employment duration. This study involved secondary data analysis of a subsample of FEP individuals (n = 65) who participated in a randomized controlled trial comparing Individual Placement and Support plus treatment as usual (TAU), versus TAU alone, over 6 months. A cognitive battery was administered at baseline and employment duration (hours) and job complexity in the longest held job over 6 months were measured. Factor analysis with promax rotation of the cognitive battery revealed 4 cognitive domains: (a) attention and processing speed; (b) verbal learning and memory; (c) verbal comprehension and fluency; and (d) visual organization and memory (VO&M). The final hierarchical regression model found that VO&M and job complexity independently predicted employment duration in longest held job; however, the "fit" (or interaction) between VO&M and job complexity was not significant. These findings suggest that VO&M and job complexity are important predictors of employment duration, but it is not necessary to ensure VO&M ability matches job complexity. However, there are limited comparative studies in this area, and other aspects of the person-organization fit perspective may still be useful to optimize vocational outcomes in FEP.

Understanding access and use of technology among youth with first-episode psychosis to inform the development of technology-enabled therapeutic interventions.

Computers, video games and technological devices are part of young people's everyday lives. However, their use in first-episode psychosis (FEP) treatment is rare. The purpose of this study was to better understand the access and use of technology among individuals with FEP, including gaming activities, to inform future development of technology-enabled therapeutic applications. Self-administered survey on use of technological tools in 71 FEP individuals. PCs/laptops were used by all participants; cellphones/smartphones by 92%, consoles by 83% (mainly male and younger participants). Women texted and used social networks more frequently; men played games (mainly action) more often. The younger individuals reported playing games frequently (32% daily) with less use of the Web and social networks (favourite: Facebook). These data will be useful for developing Web-based psychoeducation tools and cognitive remediation video games for youth with FEP.

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology

Background/Aims: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). Methods: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. Results: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. Conclusion: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology.

Sex differences in cognitive functioning in at-risk mental state for psychosis, first episode psychosis and healthy control subjects

BackgroundSeveral sex differences in schizophrenia have been reported including differences in cognitive functioning. Studies with schizophrenia patients and healthy controls (HC) indicate that the sex advantage for women in verbal domains is also present in schizophrenia patients. However, findings have been inconsistent. No study focused on sex-related cognitive performance differences in at-risk mental state for psychosis (ARMS) individuals yet. Thus, the aim of the present study was to investigate sex differences in cognitive functioning in ARMS, first episode psychosis (FEP) and HC subjects. We expected a better verbal learning and memory performance of women in all groups. MethodsThe neuropsychological data analysed in this study were collected within the prospective Früherkennung von Psychosen (FePsy) study. In total, 118 ARMS, 88 FEP individuals and 86 HC completed a cognitive test battery covering the domains of executive functions, attention, working memory, verbal learning and memory, IQ and speed of processing. ResultsWomen performed better in verbal learning and memory regardless of diagnostic group. By contrast, men as compared to women showed a shorter reaction time during the working memory task across all groups. ConclusionThe results provide evidence that women generally perform better in verbal learning and memory, independent of diagnostic group (ARMS, FEP, HC). The finding of a shorter reaction time for men in the working memory task could indicate that men have a superior working memory performance since they responded faster during the target trials, while maintaining a comparable overall working memory performance level.

EPA-1645 – The impact of cannabis use on clinical presentation in first-episode psychosis: adolescent- versus adult-onset psychosis

Cannabis use has demonstrated an association with earlier onset of psychosis. Investigation of sociodemographic and clinical characteristics in association with cannabis use in adults with first-episode psychosis (FEP) has resulted in inconsistent findings. The clinical profile of cannabis users amongst adolescents with FEP remain widely understudied. To investigate the frequency of cannabis use, and its association with sociodemographic and clinical characteristics in adolescent-versus adult-onset FEP. Naturalistic cross-sectional study of 1363 FEP cases aged 14-35 (136 with adolescent-onset psychosis) referred to Early Intervention Services for psychosis in London (UK) (2003-2009). Sociodemographic and clinical data (age of psychosis onset, symptom domains, substance misuse, insight, violence, global functioning, and duration of untreated psychosis [DUP]) were collected at entry to EIS. Cannabis users were more likely to be male (78.2%), White (43.0%) and unemployed (72.0%). No significant difference was found in cannabis abuse/dependence frequencies between adolescents (28.4%) and adults (24.7%). Cannabis abuse/dependence was associated with an earlier onset of psychosis by 2 years (p<0.001), greater manic and positive symptoms (p<0.001), increased violence (p=0.011), and poorer functioning (p=0.013) and insight (p=0.003). For adolescents, cannabis abuse/dependence was associated with greater positive symptoms, poorer functioning and longer DUP. Cannabis use shapes the clinical presentation of FEP individuals. Similar frequencies of cannabis use between age groups suggest that substance misuse services should be provided to all, aiming to reducing consumption. Greater vigilance amongst clinicians would enable earlier detection of psychosis in substance misusing adolescents, to reduce DUP and minimise associated poor outcomes.

Metacognition, symptoms and premorbid functioning in a First Episode Psychosis sample

Significant metacognitive impairments are observed in chronic psychosis samples but metacognition is less understood in first episode psychosis (FEP). The current study explored correlations between metacognition, symptoms and premorbid functioning in an FEP sample. In a cross-sectional cohort study, individuals in the first 12months of treatment metacognition were assessed with the Metacognition Assessment Scale-Revised version (MAS-R). Psychotic symptomatology, premorbid adjustment, and clinician rated service engagement were also measured. Lower scores for metacognitive understanding of other's minds were significantly correlated with greater negative symptoms, poorer early adolescent social adjustment and poorer clinician rated help-seeking. Our findings suggest that FEP individuals with difficulties in understanding other's minds have more social deficits and may be less able to make effective use of treatment.