Louise Birkedal Glenthøj

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.

The effect of cognitive remediation in individuals at ultra-high risk for psychosis: a systematic review

Cognitive deficits are prominent features of the ultra-high risk state for psychosis that are known to impact functioning and course of illness. Cognitive remediation appears to be the most promising treatment approach to alleviate the cognitive deficits, which may translate into functional improvements. This study systematically reviewed the evidence on the effectiveness of cognitive remediation in the ultra-high risk population. The electronic databases MEDLINE, PsycINFO, and Embase were searched using keywords related to cognitive remediation and the UHR state. Studies were included if they were peer-reviewed, written in English, and included a population meeting standardized ultra-high risk criteria. Six original research articles were identified. All the studies provided computerized, bottom-up-based cognitive remediation, predominantly targeting neurocognitive function. Four out of five studies that reported a cognitive outcome found cognitive remediation to improve cognition in the domains of verbal memory, attention, and processing speed. Two out of four studies that reported on functional outcome found cognitive remediation to improve the functional outcome in the domains of social functioning and social adjustment. Zero out of the five studies that reported such an outcome found cognitive remediation to affect the magnitude of clinical symptoms. Research on the effect of cognitive remediation in the ultra-high risk state is still scarce. The current state of evidence indicates an effect of cognitive remediation on cognition and functioning in ultra-high risk individuals. More research on cognitive remediation in ultra-high risk is needed, notably in large-scale trials assessing the effect of neurocognitive and/or social cognitive remediation on multiple outcomes.

Course of illness in a sample of patients diagnosed with a schizotypal disorder and treated in a specialized early intervention setting. Findings from the 3.5 year follow-up of the OPUS II study

BACKGROUND Previous studies report that 20% to 30% of those initially diagnosed with schizotypal disorder go on to develop a psychotic disorder (predominantly schizophrenia). Schizotypal disorder share some traits of those used to identify patients at ultra-high risk for psychosis. METHOD As part of a randomized clinical trial testing the effect of prolonged specialized early intervention, we recruited 83 participants diagnosed with a schizotypal disorder. Participants were recruited 18 months into their two-year treatment program, and follow-up interviews were conducted three and a half year later. They were randomized to either discontinuation after the standard two year treatment or continuation of the specialized treatment for totally five year. The study investigated whether prolonged treatment could affect the rate of transition to psychosis and other clinical outcomes, and what would predict transition to psychosis. RESULTS Of those 59 who attended the follow-up interview 19 (32%) developed a psychotic disorder at follow-up. There were no differences between the two treatment groups on transition rates or clinical outcomes. We found that lower level of functioning at baseline predicted transition to psychosis. DISCUSSION Comparable to previous ultra-high risk studies, we found that level of functioning was the strongest predictor of transition to psychosis. Prior studies have found effect of specialized early intervention on transition rates, but we were not able to reproduce this finding. This may be attributable to the intervention in our study occurring at a later stage in the illness than prior studies.

Negative symptoms mediate the relationship between neurocognition and function in individuals at ultrahigh risk for psychosis.

Neurocognition is known to impact functioning in individuals at ultrahigh risk (UHR) for psychosis, but studies investigating potential mediators of this relationship are scarce. Building on evidence from schizophrenia spectrum disorders, the study tested whether negative symptoms and social skills act as mediators between neurocognition and functional outcome in UHR individuals.

T16. GLUTAMATERGIC CHANGES IN UHR

Abstract Background The search for biomarkers may prove significant for short-term identification of UHR individuals (remission/non-remission). On a long-term basis, biomarkers might give the opportunity to delay or prevent psychotic episodes. Disturbances of the neurotransmitters glutamate and GABA have long been suspected to be involved in the pathophysiology of psychosis. These disorders have also found been found in people at UHR, making it a promising area for early detection. Cognitive deficits in schizophrenia are present prior to the onset of psychosis, and may be linked to perturbed glutamate and GABA function. Data suggest that this link is already present in UHR states. Methods Participants: UHR individuals who meet the CAARMS criteria recruited from Mental Health Services in the Capital Region of Denmark and matching healthy controls. Examinations 1H-MRS of the ACC and thalamus. Diagnostic and psychopathological tests: CAARMS, SCID, SOFAS, PSP, Cornblatt, SANS, BPRS, MADRS, YMRS, CGI, PAS, SPI-A, AQoL Cognitive tests as part of collaborative studies. Results So far 116 UHR individuals and 42 healthy controls have been scanned (December 2017) Very early preliminary analysis of the baseline data finds no significant difference in glutamate levels (in ACC and thalamus) in UHR patients compared to matched healthy controls. Baseline data remains to be analysed in relation to relevant subgroups of patients e.g. based on clinical outcome. GABA analysis and analysis of follow-up data are also yet to be performed. Data will be ready for the meeting, and will be presented. Discussion More studies are needed in this field, since results so far have been diverging. Baseline data remains to be analysed in relation to relevant subgroups of patients e.g. based on clinical outcome. GABA analysis and analysis of follow-up data are also yet to be performed. Glutamate data will be presented at the meeting.

Non-pharmacological modulation of cerebral white matter organization: A systematic review of non-psychiatric and psychiatric studies

Objective: Neuroplasticity is a well‐described phenomenon, but effects of non‐pharmacological interventions on white matter (WM) are unclear. Here we review associations between active non‐pharmacological interventions and WM organization in healthy subjects and in psychiatric patients. Method: A systematic review of non‐psychiatric and psychiatric studies in MEDLINE and EMBASE databases. We included longitudinal, controlled studies in human participants aged 18–60 years published in peer‐reviewed journals between 2000 and 2017. Studies required active interventions lasting between one day and one year, targeting cognitive‐, motor‐ or sensory domains. The primary outcome was intervention‐related brain changes in diffusion‐weighted imaging (DWI) derived measures. Results: We included 25 studies. Twenty studies reported positive findings. Five studies investigated psychiatric patients. Nine randomized, controlled trials (RCTs) reported DWI changes following cognitive interventions. Interventions were too heterogeneous to perform a meta‐analysis. Intervention duration of at least eight weeks appeared required to induce consistent WM changes. Conclusions: Non‐pharmacological interventions can induce changes in WM. DWI is a relevant correlate of e.g. cognitive training in prospective, long‐term RCTs of psychiatric patients. HIGHLIGHTSNon‐pharmacological interventions can induce changes in white matter.Minimal intervention duration of 8 weeks is required to induce consistent WM‐changes.Associations between cognitive interventions and WM is substantiated.DWI is a relevant correlate of cognitive training in RCTs of psychiatric patients.

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).

Examining speed of processing of facial emotion recognition in individuals at ultra-high risk for psychosis: Associations with symptoms and cognition

Emotion recognition is an aspect of social cognition that may be a key predictor of functioning and transition to psychosis in individuals at ultra-high risk (UHR) for psychosis (Allott et al., 2014). UHR individuals exhibit deficits in accurately identifying facial emotions (van Donkersgoed et al., 2015), but other potential anomalies in facial emotion recognition are largely unexplored. This study aimed to extend current knowledge on emotion recognition deficits in UHR individuals by examining: 1) whether UHR would display significantly slower facial emotion recognition than healthy controls, 2) whether an association between emotion recognition accuracy and emotion recognition latency is present in UHR, 3) the relationships between emotion recognition accuracy, neurocognition and psychopathology in UHR.