Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

Background Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. Methods In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. Results In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. Conclusions We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning.

Risk factors for repeated emergency compulsory psychiatric admissions

Background The characteristics of patients who have repeated compulsory psychiatric admissions are largely unknown. Aims To investigate the frequency and risk factors for repeated emergency compulsory psychiatric admission (ECPA); and to identify targets for interventions to reduce repeated ECPA. Method Data were collected from a database of electronic patient files (EPFs) held by three psychiatric emergency services (PES) in the Netherlands. Analyses were based on the data for adult patients (aged 18–75 years) with a first PES contact in 2010–2015. Using descriptive statistics and regression analysis, we studied the associations between baseline patient factors and repeated ECPA and time to readmission, within a 2-year follow-up period. Results We included 6059 patients: 15.6% had two or more ECPAs. In total, 66% of second ECPAs had occurred within 6 months of the first. About 30% of all ECPAs were repeated ECPAs. Two baseline factors were associated with a higher frequency of a second ECPA: history of receiving any mental healthcare treatment, whether in-patient or out-patient or both, and a lower level of self-care. Three were associated with a lower frequency: ethnicity (other than Dutch), older age and suicidality. Lower Global Assessment of Functioning (GAF) scores and housing problems were associated with a shorter time to compulsory readmission and persistent psychiatric problems with a longer time to compulsory readmission. Conclusions We found that 15.6% of patients had two or more ECPAs. Two-thirds of the second ECPAs had occurred within 6 months of the first. Like earlier studies, the risk factors we identified suggest that interventions to reduce the risk of repeated compulsory psychiatric admission should seek to improve self-care, general daily functioning and homelessness.

S121. OPUS 20, 20 YEAR FOLLOW-UP ON THE OPUS TRIAL

Background Since the first OPUS trial 20 years ago, structured clinical assessments have been collected from a cohort of first episode psychosis patients at 2, 5 and 10 years follow-up. They found that the symptomatology of patients clustered in distinct groups, and they were able to determine stable long-term trajectories of positive and negative symptoms. The Suffolk County Medical health project has followed patients after a first episode psychosis for 20 years. They also found a stable course of trajectories but with an overall significant worsening of symptom severity over time. The 20 year OPUS follow-up will give us the first opportunity to assess the long term outcome in a large representative cohort treated within modern mental health services with treatment available for all. Methods From 1998 to 2000 578 participants were randomized to OPUS or TAU. Baseline characteristics of the cohort were as follows: mean age 26.6 years, 59% were males, 66% had a diagnosis of schizophrenia and 27% had a secondary diagnosis of alcohol or substance abuse At the 20 year follow-up the investigators will be blinded to the original treatment allocation. The patients who wish to participate will be assessed using SAPS, SANS, SCAN, PSP and GAF. Socio-demographic factors and suicidal ideation will be register via self report. Cognitive function will be tested using BACS and all participants will be asked to fill out a number of self-rating questioners including WHO quality of life-BREF, self-perceived health, strengths and difficulties, the parenting scale and self-perceived negative symptoms. Using national Danish registers we can collect information on all former participants regarding the use of psychiatric and general healthcare services, medication, supported housing or homelessness, employment status, substance abuse and mortality. Results The OPUS 20 study started collecting data in Jan 2018. We are attempting to contact as many patients as possible from the 578 participants in the original OPUS cohort. At the time of writing we had included data and attempted contact to 322 participants. Overall 104 people (31,7%) have agreed to participate in the interviews. In the follow-up 10 years ago, the participation-rate was 60% so this is a big drop in participation rate. 41 (14%) have died, 31 (9,5%) were lost due to emigration, homelessness or hidden identity and/or disempowerment. 70 (21,3%) didn’t wish to participate and 76 (23,2%) never responded. Discussion Psychotic disorders and schizophrenia in particular are associated with progressive worsening of symptoms and profound social impairment, and as such are still very stigmatized. Results from the 10 year OPUS follow-up found stable trajectories of positive and negative symptoms over time, with a tendency of reduction and stabilization of positive symptoms but less variation of negative symptoms. They found poor but stable social functioning with a mean GAF score of 55 after 10 years. The Suffolk County mental health project also found stable trajectories of psychopathology measured with SAPS and SANS. They however found progressive worsening of GAF scores declining form 49 points at the beginning to 36 after 20 years. So far we have seen stable GAF scores and SAPS and SANS scores compared to OPUS 10. This gives rise to some optimism about the prognosis for schizophrenia compared to the findings of the Suffolk study. In our study the extensive interviews combined with the data collected form Danish registers give us a unique opportunity to look at the long term course of illness after FEP. The ability to test if previous findings are robust over time will be essential to the development of targeted interventions, differentiated to the needs of different patient groups.

S64. COGNITIVE IMPAIRMENTS AND PREDICTION OF FUNCTIONAL OUTCOME IN INDIVIDUALS AT CLINICAL HIGH-RISK FOR PSYCHOSIS

Background Research in individuals at clinical-high risk for psychosis (CHR-P) has focused on developing algorithms to predict transition to psychosis. However, it is becoming increasingly important to address other outcomes, such as the level of functioning of CHR-P participants. To address this important question, this study investigated the relationship between baseline cognitive performance and functional outcome between 6–12 months in a sample of CHR-P individuals using a machine-learning approach to identify features that are predictive of long-term functional impairments. Methods Data was available for 111 CHR-P individuals at 6–12 months follow-up. In addition, 47 CHR-negative (CHR-N) participants who did not meet CHR criteria and 55 healthy controls (HCs) were recruited. CHR-P status was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult version (SPI-A). Cognitive assessments included the Brief Assessment of Cognition in Schizophrenia (BACS) and the Penn Computerized Neurocognitive Battery (CNB). Global, social and role functioning scales were used to measure functional status. CHR-P individuals were divided into good functional outcome (GFO, GAF ≥ 65) and poor functional outcome groups (PFO, GAF < 65). Feature selection was performed using LASSO regression with the LARS algorithm and 10-fold cross validation with GAF scores at baseline as the outcome variable. The following features were identified as predictors of GAF scores at baseline: verbal memory, verbal fluency, attention, emotion recognition, social and role functioning and SPI-A distress. This model explained 47% of the variance in baseline GAF scores. In the next step, Support Vector Machines (SVM), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Gaussian Naïve Bayes (GNB), and Random Forest (RF) classifiers with 10-fold cross validation were then trained on those features with GAF category at follow-up used as the binary label column. Models were compared using a calculated score incorporating area under the curve (AUC), accuracy, and AUC consistency across runs, whereby AUC was given a higher weighting than accuracy due to class imbalance. Results CHR-P individuals had slower motor speed, reduced attention and processing speed and increased emotion recognition reaction times (RTs) compared to HCs and reduced attention and processing speed compared to CHR-Ns. At follow-up, 66% of CHR-P individuals had PFO. LDA emerged as the strongest classifier, showing a mean AUC of 0.75 (SD = 0.15), indicating acceptable classification performance for GAF category at follow-up. PFO was detected with a sensitivity of 75% and specificity of 58%, with a total mean weighted accuracy of 68%. Discussion The CHR-P state was associated with significant impairments in cognition, highlighting the importance of interventions such as cognitive remediation in this population. Our data suggest that the development of features using machine learning approaches is effective in predicting functional outcomes in CHR-P individuals. Greater levels of accuracy, sensitivity and specificity might be achieved by increasing training sets and validating the classifier with external data sets. Indeed, machine learning methods have potential given that trained classifiers can easily be shared online, thus enabling clinical professionals to make individualised predictions.

Predictors of psychosocial outcome of bipolar disorder: data from the Stanley Foundation Bipolar Network

Background Impairments in psychosocial functioning have been demonstrated in 30–60% of adults with bipolar disorder (BD). However, the majority of studies investigating the effect of comorbid mental health disorders and age at onset outcomes in BD have focused on traditional outcome measures such as mood symptoms, mortality and treatment response. Therefore, this project aimed to investigate the impact of comorbid mental health disorders and age at onset on longitudinal psychosocial outcome in participants with BD. Method Mixed effects modelling was conducted using data from the Stanley Foundation Bipolar Network. Baseline factors were entered into a model, with Global Assessment of Functioning (GAF) score as the longitudinal outcome measure. Relative model fits were calculated using Akaike’s Information Criterion. Results No individual comorbidities predicted lower GAF scores, however an interaction effect was demonstrated between attention deficit hyperactivity disorder (ADHD) and any anxiety disorder (t = 2.180, p = 0.030). Participants with BD I vs BD II (t = 2.023, p = 0.044) and those in the lowest vs. highest income class (t = 2.266, p = 0.024) predicted lower GAF scores. Age at onset (t = 1.672, p = 0.095) did not significantly predict GAF scores. Conclusions This is the first study to demonstrate the negative psychosocial effects of comorbid anxiety disorders and ADHD in BD. This study adds to the growing database suggesting that comorbid mental health disorders are a significant factor hindering psychosocial recovery.

Duration of untreated psychosis of first-episode psychotic disorders in Yogyakarta, Indonesia

Introduction: Duration of untreated psychosis (DUP) is an important predictor for prognosis in first episode of psychotic disorders. Caregivers often seek help from alternative healers first and health professional later. These would delay proper treatments for the patients, resulting in more severe symptoms and lower functioning on their visit to medical facility. The present study aims to find the association between DUP, symptoms severity, and global functioning in patients with first-episode psychotic disorders. Methods: We identified 100 patients with first episode of psychotic disorders and their caregivers. The instruments used were Brief Psychotic Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Premorbid Schizoid-Schizotypal Traits (PSST), and Global Assessment of Functioning (GAF). Results: There were no significant association between BPRS, PANSS, PSST, and GAF scores and DUP in our subjects. Nevertheless, we found that men had significantly longer DUP compared to women. Conclusion: We found significant association between sex and DUP in this study. Longer DUP leads to delayed treatments and poorer prognosis. Further study is required to confirm our finding.

The Swedish version of the Sheehan Disability Scale - a valid and brief measure of functioning

Rationale, aims and objective: The Sheehan Disability Scale (SDS) is a brief instrument used to measure functional disability, but the Swedish translation has not been psychometrically evaluated. The aim of this paper is to test the psychometric properties of the Swedish translation and to further examine concurrent and external validity.Method: In this cross-sectional study, 160 young psychiatric patients from an open care unit in Sweden, were recruited based on a clinical diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD) and/or Borderline Personality Disorder (BPD) and re-diagnosed for confirmation. Participants were interviewed concerning socio-demographic data and a socio-demographic index (SDI) was constructed. Reliability of SDS was measured as internal consistency and an exploratory factor analysis was performed. Level of functioning was measured by SDS scores and Global Assessment of Functioning (GAF). SDS, both self-assessed and expert rated and GAF scores were compared to measure concurrent validity, while SDS and the SDI were compared to measure external validity.Results: The Swedish SDS had a Cronbach’s alpha coefficient of 0.77. An exploratory factor analysis showed that the SDS-items loaded on a single factor with an eigenvalue of 2.06. Self-assessed SDS-scores correlated with expert rated GAF-scores (r = -0.606) and, to some extent, with SDI scores (r = 0.280). Patients with an SDI score ≥ 1 had higher SDS-scores (t=2.70, p=0.008).Conclusions: The Swedish SDS has similar psychometric properties as the English and Spanish versions. It showed both concurrent and external validity, but external validity was weaker

Substance abuse in first episode psychosis: Baseline characteristics and clinical outcome

IntroductionThere are high rates of substance use disorders (SUD) amongst first episode psychosis (FEP). SUD have been linked to better premorbid adjustment, more severe positive and negative symptoms at presentation and poorer symptomatic and functional outcome [1]. Moreover, shorter duration of untreated psychosis (DUP) has been described as an important predictor of outcome in FEP [2].AimsWith this study, we want to know which baseline characteristics and clinical outcomes differ between FEP patients with and without substance use.MethodsOne hundred and seventy-five FEP were consecutively admitted to Hospital del Mar since January 2008 to September 2014 and entered the FEP programme of the institution. The included evaluation was socio-demographic and clinical data at baseline and 1 year follow-up. We studied differences in age, gender, DUP, GAF scores at baseline and 1 year follow-up and PANSS subscale scores at base and 1 year follow-up between substance users and non-users.ResultsCannabis: we found that users were significative younger (P < 0.01), had a higher proportion of males (P < 0.01) and a significative shorter DUP in users (P = 0.008).Alcohol: we found that users were significative younger (P < 0.009), had a higher proportion of males (P < 0.003) and a significative lower PANNS negative scores at baseline (P = 0.01) and 1 year follow-up (P = 0.03).ConclusionsIn our sample of first episode psychosis, cannabis and alcohol use is linked with a younger age and a high proportion of males. Moreover, it seems that cannabis use could be associated with a shorter DUP.References not available.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Exploring Outcome and Validity of the GAF in Psychiatric Inpatient Care

A small number of studies have investigated predictive factors in relation to the Global Assessment of Functioning (GAF) scale. This study aimed to explore the influence of clinical and socio-demographic factors in a psychiatric inpatient setting in relation to treatment outcome measured by the GAF. The studied psychiatric inpatient sample consisted of 816 episodes of care, with GAF ratings made at both admission and discharge. Multiple linear regressions were performed to analyze what variables predicted GAF scores at admission and at discharge. Significant predictors of GAF scores at admission were age, schizophrenia, other psychotic disorders, and no registered diagnosis. GAF scores at admission, patients’ diagnoses, and ward affiliation were able to significantly predict GAF at discharge. Specialized wards did not necessarily deliver the best treatment results in spite of their diagnostic specialization. This study provides support to the construct validity of the GAF when used as a measure of outcome.

Short-term functional outcome and premorbid adjustment in clinical high-risk patients. Results of the EPOS project

PurposeIn patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment.MethodsIn all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed.ResultsDuring the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model.ConclusionA great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.