T.H. McGlashan

Premorbid Adjustment, Onset Types, and Prognostic Scaling: Still Informative?

Efforts emerged to describe, quantify, and predict prognosis once it became clear that the outcomes of Kraepelinian dementia praecox could vary. The concepts and scales that have evolved focus on types of premorbid adjustment and illness onset. Enduring highlights of this literature will be described, and its current and future utility will be discussed.

Insights into psychosis risk from leukocyte microRNA expression.

Dysregulation of immune system functions has been implicated in schizophrenia, suggesting that immune cells may be involved in the development of the disorder. With the goal of a biomarker assay for psychosis risk, we performed small RNA sequencing on RNA isolated from circulating immune cells. We compared baseline microRNA (miRNA) expression for persons who were unaffected (n=27) or who, over a subsequent 2-year period, were at clinical high risk but did not progress to psychosis (n=37), or were at high risk and did progress to psychosis (n=30). A greedy algorithm process led to selection of five miRNAs that when summed with +1 weights distinguished progressed from nonprogressed subjects with an area under the receiver operating characteristic curve of 0.86. Of the five, miR-941 is human-specific with incompletely understood functions, but the other four are prominent in multiple immune system pathways. Three of those four are downregulated in progressed vs. nonprogressed subjects (with weight -1 in a classifier function that increases with risk); all three have also been independently reported as downregulated in monocytes from schizophrenia patients vs. unaffected subjects. Importantly, these findings passed stringent randomization tests that minimized the risk of conclusions arising by chance. Regarding miRNA–miRNA correlations over the three groups, progressed subjects were found to have much weaker miRNA orchestration than nonprogressed or unaffected subjects. If independently verified, the leukocytic miRNA biomarker assay might improve accuracy of psychosis high-risk assessments and eventually help rationalize preventative intervention decisions.

Longitudinal changes in social cognition in individuals at clinical high risk for psychosis: An outcome based analysis

Social cognition deficits have been observed in individuals at clinical high risk (CHR) for psychosis. Longitudinal change in social cognition were analyzed in CHR individuals from the North American Prodrome Longitudinal Study (NAPLS2) based on outcome at 24 months. Individuals (n = 359) were classified into remission, symptomatic, prodromal progression and transition to psychosis (CHR-T) groups. Social cognition was assessed using theory of mind, emotion perception, and social perception tasks. There were no differences at baseline or 24 months between the groups on social cognition. Non-transition groups improved significantly over time on social cognition, but CHR-T did not show this effect.

S01-01 - Early Detection in Psychosis: 5 year Outcome in the Scandinavian Tips-Study

Background During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long term outcome. This study reports the effects of reducing DUP on 5-year course and outcome. Methods During 1997-2000 a total of 281 consecutive patients aged > 17 years with first episode non-affective psychosis were recruited of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) program with public information campaigns and low-threshold psychosis detection teams was established in one health-care area (ED-area), but not in a comparable area (No-ED area). Both areas ran equivalent treatment programs during the first 2 years and need-adapted treatment thereafter. Results At the start of treatment ED-patients had shorter DUP and less symptoms than No-ED-patients. There were no significant differences in treatment (psychotherapy and medication) for the 5 years. Mixed-effects modeling showed better scores for the ED-group on PANSS negative, depressive and cognitive factors and for GAF social functioning at 5 year follow-up. The ED-group also had more contacts with friends. Regression analysis did not find that these differences could be explained by confounders. Conclusions Early treatment had positive effects on clinical and functional status at 5 year follow-up in first episode psychosis.

126 - PERSISTENT DRUG ABUSE IN FIRST EPISODE PSYCHOSIS - 1- AND 2-YEAR OUTCOME

Yale University School of Medicine, New Haven, CT, USAPresenting Author details: tklarsen@online.noArmauer Hansensv 20, 4068 Stavanger, Norway,Tel.: +47 90832795.Background: Abuse of drugs and alcohol is common in first episodepsychosis and frequently linked to poorer outcome [1]**. However,these results are mostly based on samples that are small and/or havelimitedgeneralizability.Theobjectiveofthisistolookat1-and2-yearoutcome in patients with first episode non-affective psychosis withemphasis on the predictive power of abuse of drugs and/or alcoholmeasured at index admission.Methods:Afollow-upstudywithaclinicalepidemiologicalsampleoffirst episode psychosis in patients recruited from four sites [sf1] inScandinavia (three in Norway and one in Denmark). All patients wereassessed on abuse of drugs/alcohol; premorbid functioning, socialfunctioning, and symptom level at admission and symptomatic andfunctional outcome after 1 and 2 years of treatment. All patients wereoffered a similar treatment package containing antipsychotics, familywork and individual psychotherapy.Results: Drug and alcohol abuse at index admission predicted a greaternumber of relapses, poorer social functioning (GAF) and less stableemploymentstatusatboth1-and 2-yearfollow-up.Approximately50%hadstoppedabusingdrugsat1-and2-yearsfollow-up.Persistentabusersat 2 years of follow-up were more often chronically psychotic, had ahighernumberofrelapsesandmoresymptoms(positiveandexcitement)compared to non-abusers. Similar results were found for 1-year follow-up.Thesmallgroup(6%)thatstartedabusingdrugshadmoredepressivesymptoms and the lowest GAF-scores.Conclusions: Persistent abuse is a difficult and significant problem infirst episode psychosis and this study demonstrated poorer outcome inpersistent abusers. However, almost 50% of our sample stopped theabuse during the first 2 years after index admission.Reference:[1] Larsen TK, Melle I, Auestad B, et al. Substance abuse in first-episode non-affective psychosis. Schizophr Res 2006; 88: 55–62.doi:10.1016/j.schres.2007.12.193127 – SUICIDALITY IN FIRST EPISODE PSYCHOSISR. McCaul

Neurocognitive dysfunction in first-episode psychosis: Correlates with symptoms, premorbid adjustment, and duration of untreated psychosis (DUP)

OBJECTIVE The authors examined the relationship of neurocognitive function with duration of untreated psychosis, premorbid illness factors, and clinical symptoms to determine whether long duration of untreated psychosis independently compromises cognitive function. METHOD Patients recruited to a study of the effect of an early detection program on the duration of untreated first-episode psychosis in two catchment areas were compared to patients in a similar treatment program in two other catchment areas without an early detection program. The median duration of untreated psychosis was 10.5 weeks for all patients. A total of 301 patients entered the study, and 207 completed a comprehensive neuropsychological test battery that assessed working memory/fluency, executive function, verbal learning, impulsivity, and motor speed. The median time from start of treatment to neuropsychological testing was 108 days; all patients were tested within 9 months. RESULTS No significant association was found between duration of untreated psychosis and any of the cognitive measures. Strong associations were demonstrated between poorer premorbid school functioning and neurocognitive deficits, especially in verbal learning and working memory. No relationship was found between neurocognitive functions and clinical measures, except for an inverse correlation of Positive and Negative Syndrome Scale negative symptoms and working memory and a positive correlation between positive symptoms and motor speed. CONCLUSIONS The data contribute to a disconfirmation of the hypothesis of an association between duration of untreated psychosis and neurocognitive performance at baseline.