The association between depressive symptoms, cognitive function, and inflammation in major depression.

The purpose of this study was to assess the association between IL-6 and CRP with depressive items and cognitive function. We included 112 outpatients with major depression from an exercise trial and 57 healthy controls. IL-6, high sensitive CRP (hsCRP), and cognitive function were assessed in all subjects. After baseline assessment, patients were randomised to either a 3months exercise intervention or an exercise control group. Post-intervention IL-6, hsCRP, depressive symptoms, and cognitive function were reassessed in the patient group. IL-6 and hsCRP were significantly increased in depressed patients compared to healthy controls (p=0.02 and 0.04). These differences were no longer significant after adjustment for lifestyle associated variables. We found no association between immune markers and specific depressive symptoms at baseline or as change over time. Regarding the cognitive tests, IL-6 was positively associated with Serial sevens (p=0.008) and hsCRP was inversely associated with Trail making A (p=0.02) and design fluency (p=0.001) at baseline. At 3months follow-up IL-6 and hsCRP levels did not significantly change from baseline and did not differ between the two patient groups. Depression scores was lower compared to baseline but did not differ between groups. Combining the two groups, a decrease in IL-6 was associated to decreased verbal fluency (p=0.02), and a decrease in hsCRP was associated with improvement in Trail making A (p=0.005). In conclusion, the level of IL-6 and hsCRP was increased in depressed outpatients but was not associated to specific depressive symptoms. In terms of cognitive function, we found that higher hsCRP levels were associated to lower psychomotor speed both at baseline and at follow-up.

Test-retest reliability of the Danish Adult Reading Test in patients with comorbid psychosis and cannabis-use disorder.

BACKGROUND: The New Adult Reading Test is a common instrument for assessing pre-morbid IQ for patients with, for instance, schizophrenia. However, test-retest reliability has not been established for patients dually diagnosed with psychosis and substance use disorder. Furthermore, test-retest reliability of the Danish adaptation has never been established in any population. AIMS: To determine the test-retest reliability of the Danish Adult Reading Test (DART) (adapted from the National Adult Reading Test, NART) for patients dually diagnosed with psychosis and cannabis-use disorder. METHODS: This was a secondary analysis of the CapOpus randomized trial. As part of the trial, 103 patients were randomized, and completed the DART up to three times. Pearson's r and pairwise t-tests were calculated. RESULTS: DART score was independent of randomization, cannabis-use frequency and psychopathology. Scores at the last interview were slightly higher than at the first two. Correlation over time was very strong (0.8 < r <0.9) for all pairwise comparisons of interviews. Variations in DART scores and estimated pre-morbid IQ over time were sometimes of borderline statistical significance but not of clinical relevance. CONCLUSIONS: DART and NART have high test-retest reliability, but apparently non-systematic, clinically irrelevant variation over time does occur. CLINICAL IMPLICATION: The Danish adaptation of the New Adult Reading Test possesses good test-retest reliability, making it an appropriate choice for assessment of pre-morbid IQ, and in patients with dually diagnosed psychosis and cannabis-use disorder.

Cognitive and clinical predictors of functional capacity in patients with first episode schizophrenia.

BACKGROUND: The predictors of functional capacity in first episode schizophrenia among seven separable cognitive domains and clinical variables are unknown. AIM: To investigate predictors of functional capacity in first episode schizophrenia and the associations between functional capacity and measures of real-world functioning. METHODS: Socio-demographic, clinical, and cognitive measures from a sample of patients with first episode schizophrenia spectrum disorders aged 18-34years (N=117) were examined at baseline, 4-month follow-up, and 10-month follow-up and used to predict concurrent and longitudinal functional capacity. Symptoms were assessed with the Positive and Negative Syndrome Scale, cognitive functioning with the MATRICS Cognitive Consensus Battery, and functional capacity with the brief version of the University of California San Diego Performance-based Skills Assessment. Linear and logistic regression analyses were adjusted for age, gender, and site. RESULTS: Working memory, negative symptoms, and social cognition accounted for 41% of the variance in functional capacity at baseline. Longitudinally, verbal learning, working memory, and negative symptoms predicted 4-month functional capacity. Working memory and visual learning predicted 10-month functional capacity. Functional capacity was associated to global functioning in the univariate analysis, but in multivariable analyses global functioning, financial independence, and independent living were predicted by negative symptoms or general symptoms explaining 15-23% of the variance. CONCLUSIONS: The strongest single predictor of functional capacity is working memory, followed by negative symptoms. Clinical symptoms, but not functional capacity, predicted real-world functioning. The usability of the UPSA-B in first episode schizophrenia is discussed. Neurocom, ClinicalTrials.gov Identifier: NCT00472862, http://clinicaltrials.gov/ct2/show/NCT00472862?term=neurocom&rank=1.

Cognitive training plus a comprehensive psychosocial programme (OPUS) versus the comprehensive psychosocial programme alone for patients with first-episode schizophrenia (the NEUROCOM trial): a study protocol for a centrally randomised, observer-blinded multi-centre clinical trial.

BACKGROUND: Up to 85% of patients with schizophrenia demonstrate cognitive dysfunction in at least one domain. Cognitive dysfunction plays a major role in functional outcome. It is hypothesized that addition of cognitive training to a comprehensive psychosocial programme (OPUS) enhances both cognitive and everyday functional capacity of patients more than the comprehensive psychosocial programme alone. METHODS: The NEUROCOM trial examines the effect on cognitive functioning and everyday functional capacity of patients with schizophrenia of a 16-week manualised programme of individual cognitive training integrated in a comprehensive psychosocial programme versus the comprehensive psychosocial programme alone. The cognitive training consists of four modules focusing on attention, executive functioning, learning, and memory. Cognitive training involves computer-assisted training tasks as well as practical everyday tasks and calendar training. It takes place twice a week, and every other week the patient and trainer engage in a dialogue on the patient's cognitive difficulties, motivational goals, and progress in competence level. Cognitive training relies on errorless learning principles, scaffolding, and verbalisation in its effort to improve cognitive abilities and teach patients how to apply compensation strategies as well as structured problem solving techniques. At 16-week post-training and at ten-months follow-up, assessments are conducted to investigate immediate outcome and possible long-term effects of cognitive training. We conduct blinded assessments of cognition, everyday functional capacity and associations with the labour market, symptom severity, and self-esteem. DISCUSSION: Results from four-month and ten-month follow-ups have the potential of reliably providing documentation of the long-term effect of CT for patients with schizophrenia. TRIAL REGISTRATION: Clinicaltrials.gov NCT00472862.

Design paper: The CapOpus trial: a randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis.

BACKGROUND: A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. OBJECTIVES: The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. DESIGN: The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient.The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00484302.