Kristine Krakauer

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.

Premorbid adjustment in individuals at ultra-high risk for developing psychosis: a case-control study

Deterioration in premorbid adjustment is related to ultra‐high risk (UHR) individuals developing psychosis, but it has not been examined how UHR individuals’ development differs compared to healthy controls. This study investigates differences in premorbid adjustment between UHR individuals and a healthy control group.

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.

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.

Multiple measures of HPA axis function in ultra high risk and first-episode schizophrenia patients

INTRODUCTION Abnormalities within hypothalamus-pituitary-adrenal (HPA) axis might interact with other neurobiological systems to enhance the risk of psychosis. Most of the neurodevelopmental and HPA axis changes occur in adolescence; this is also the period when prodromal and psychotic symptoms occur for the first time. More knowledge about how various stress components interact can advance understanding of the link between psychosis and the HPA axis. METHOD We examined 41 ultra high-risk (UHR) patients and 40 antipsychotic-naïve first-episode schizophrenia (FES) patients and compared them with 47 matched controls. The Perceived Stress Scale and the Recent Life Events Questionnaire were used to assess the stress levels. Day-time saliva samples were taken to measure cortisol. The pituitary gland volume was measured manually on the structural MRI using stereology. RESULTS Only the UHR patients, had a higher cortisol increase just after awakening (p = 0.009) compared to healthy controls. In UHR patients, we found a negative correlation between cortisol increase after awakening and symptom severity (p = 0.008). Pituitary gland volume and diurnal cortisol were not significantly different among the three groups. There was no correlation between pituitary gland volume, perceived stress/recent life events and any of the cortisol measures or symptoms. CONCLUSION Symptom severity during the very early phase of illness (UHR) seems to be associated with altered cortisol increase. Longitudinal studies in UHR patients would be useful to examine how stress levels affect the course of the illness.

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.