Lasse Randers

The FOCUS trial: cognitive remediation plus standard treatment versus standard treatment for patients at ultra-high risk for psychosis: study protocol for a randomised controlled trial.

BackgroundCognitive deficits are a distinct feature among people at ultra-high risk (UHR) for psychosis and pose a barrier to functional recovery. Insufficient evidence exists on how to ameliorate these cognitive deficits in patients at UHR for psychosis and hence improve daily living and quality of life. The aim of the trial is to investigate whether cognitive remediation can improve cognitive and psychosocial function in patients at UHR for psychosis.MethodsThe FOCUS trial (Function and Overall Cognition in Ultra-high risk States) is a randomised, parallel group, observer-blinded clinical trial enrolling 126 patients meeting the standardised criteria of being at UHR for psychosis. Patients are recruited from psychiatric in- and outpatient facilities in the Copenhagen catchment area. Patients are randomised to one of the two treatment arms: cognitive remediation plus standard treatment versus standard treatment. The cognitive remediation consists of 24 weekly group-based and manualised sessions targeting neurocognition and social cognition. In addition to the group sessions, the patients will be offered 12 individual sessions aiming at maximising the transfer of the effects of the cognitive training to their everyday lives. Follow-up assessments will be conducted at 6 and 12 months after randomisation. The primary outcome is the composite score on the Brief Assessment of Cognition in Schizophrenia at cessation of treatment after 6 months. Secondary outcomes are social and daily functioning, psychosis-like symptoms, negative symptomatology, and depressive symptomatology as measured with the Personal and Social Performance Scale, Brief Psychiatric Rating Scale-Expanded Version, Scale for the Assessment of Negative Symptoms, and the Montgomery-Åsberg Depression Rating Scale.DiscussionThis is the first trial to evaluate the effects of neurocognitive and social cognitive remediation in UHR patients. The FOCUS trial results will provide evidence on the effect of targeted and comprehensive cognitive rehabilitation on cognition, daily living, and symptomatology as well as long-term outcome in preventing transition to psychosis in UHR patients.Trial registrationClinicalTrials.gov NCT 02098408. Date of registration 18 March 2014.

Patterns of white matter microstructure in individuals at ultra-high-risk for psychosis: associations to level of functioning and clinical symptoms

BACKGROUND Individuals at ultra-high-risk (UHR) for psychosis present with emerging symptoms and decline in functioning. Previous univariate analyses have indicated widespread white matter (WM) aberrations in multiple brain regions in UHR individuals and patients with schizophrenia. Using multivariate statistics, we investigated whole brain WM microstructure and associations between WM, clinical symptoms, and level of functioning in UHR individuals. METHODS Forty-five UHR individuals and 45 matched healthy controls (HCs) underwent magnetic resonance diffusion tensor imaging (DTI) at 3 Tesla. UHR individuals were assessed with the Comprehensive Assessment of At-Risk Mental States, Scale for the Assessment of Negative Symptoms, and Social and Occupational Functioning Assessment Scale. Partial least-squares correlation analysis (PLSC) was used as statistical method. RESULTS PLSC group comparisons revealed one significant latent variable (LV) accounting for 52% of the cross-block covariance. This LV indicated a pattern of lower fractional anisotropy (FA), axial diffusivity (AD), and mode of anisotropy (MO) concomitant with higher radial diffusivity (RD) in widespread brain regions in UHR individuals compared with HCs. Within UHR individuals, PLSC revealed five significant LVs associated with symptoms and level of functioning. The first LV accounted for 31% of the cross-block covariance and indicated a pattern where higher symptom score and lower level of functioning correlated to lower FA, AD, MO, and higher RD. CONCLUSIONS UHR individuals demonstrate complex brain patterns of WM abnormalities. Despite the subtle psychopathology of UHR individuals, aberrations in WM appear associated with positive and negative symptoms as well as level of functioning.

Psychopathology and social functioning of 42 subjects from a Danish ultra high‐risk cohort

To make a thorough characterization of the co‐morbidity, psychopathology and demographics in the first Danish ultra high‐risk (UHR) sample.

O7.7. COGNITIVE FUNCTIONING FOLLOWING DISCONTINUATION OF ANTIPSYCHOTIC MEDICATION: A SUB-GROUP ANALYSIS FROM THE OPUS II TRIAL

Abstract Background The presence of cognitive defects in patients suffering from schizophrenia is well established. While the earlier “Kraepelinian” view was one of deteriorating cognitive functioning, more recent studies have found that cognitive deficits tend to be stable or improving over time. Cognitive impairments are associated with poorer functional outcomes and understanding the factors that influence cognitive functioning is critical for understanding how to improve cognitive and functional outcomes in patients. The effect of antipsychotics medication on cognitive functioning in patients diagnosed with schizophrenia is poorly understood. Some studies of second-generation antipsychotics indicated that they improved cognitive functioning while other studies have found that they decrease the level of cognitive functioning. Methods We included patients with schizophrenia who were in treatment with antipsychotics 1.5 years (baseline) after initiation of treatment and followed them up 3.5 years later (n=189). At follow-up 60 (32%) had discontinued their antipsychotic treatment and 129 (68%) were still taking antipsychotics. Using the Brief Assessment of Cognition in Schizophrenia (BACS) we assessed cognition at baseline and follow-up. Results The patients who had discontinued their medication had a higher level of cognitive functioning in all domains at baseline, as well as Global cognitive function (mean z-score -1.50 (SD 1.24) vs. -2.27 (SD 1.30), p<.001). After controlling for relevant confounders (age, sex, baseline functioning and negative symptoms) those who discontinued antipsychotic medication improved significantly more than those who remained on antipsychotic medication during the course of the follow-up on the Token Motor Task (estimated mean change difference -0.46, 95% CI(-0.89; -0.04), p=0.031), the Speed of Processing Domain (estimated mean change difference -0.38, 95% CI(-0.68; -0.08), p=0.012), and Global cognition (estimated mean change difference -0.36, 95% CI(-0.66; -0.07), p=0.016). Discussion Due to the naturalistic design we cannot conclude on the direction of the relationship between antipsychotic medication and cognition. There is no evidence that discontinuation of medication had a negative effect on cognitive functioning. Rather, we find that that discontinuation of medication was associated with better cognitive functioning.

White matter maturation during 12 months in individuals at ultra-high-risk for psychosis

The neurodevelopmental hypothesis of psychosis suggests that disrupted white matter (WM) maturation underlies disease onset. In this longitudinal study, we investigated WM connectivity and compared WM changes between individuals at ultra‐high‐risk for psychosis (UHR) and healthy controls (HCs).