Hormonal and Inflammatory Biomarkers and Response to a Cognitive Remediation Therapy in Recent-onset Psychosis: Randomized, Cross-over, Single-blind, Pilot Clinical Trial

Cognitive dysfunction is a core feature of schizophrenia experienced by approximately 75% of the patients. It may occur at the early stages of psychosis, and it is usually unaltered despite positive symptom remission. Cognitive function at psychosis onset is what most strongly predicts worse long-term overall functioning as well as worse functionality in social and occupational areas. Cognitive remediation therapy (CRT) is an intervention targeting cognitive deficit using scientific principles of learning with the ultimate goal of improving functional outcomes. It has been shown to have a significant impact on cognition with medium effect sizes. Some studies have shown improvements in recent-onset psychosis patients reporting moderate to large effects on cognitive outcomes, such as verbal and working memory, visuospatial ability, psychosocial functioning, problem-solving, or executive functioning.

Although CRT is an effective approach, there are data showing that 25-44% of the participants receiving this intervention will not improve. To date, only a limited number of studies have considered potential biomarkers that could predict the treatment response. Hormones and inflammatory markers are potential biomarkers that could moderate the response to CRT because they play important roles in cognitive function in psychiatric and non-psychiatric populations. Previous studies have suggested that hypothalamic-pituitary-adrenal axis hormones (e.g. cortisol), prolactin, thyroid hormones, and inflammatory markers are associated with cognitive performance.

Twenty-eight patients with a recent-onset psychosis aged between 18 and 40 years old and with less than 3 years of duration of the illness will be recruited. Psychotic disorders will include the following DSM-IV diagnosis: schizophrenia, schizoaffective disorder, bipolar disorder, or psychotic disorder not otherwise specified. The patients will be recruited from the Early Intervention Service from Hospital Universitari Parc Taulí Sabadell, (Spain). All participants will be outpatients with stable illness (<4 points in each positive item of the Positive and Negative Syndrome Scale (PANSS) and being on community treatment for at least 4 weeks).

A randomized crossover clinical trial will be performed: one group will first receive computerized CRT (n=14) for three months, and the other group will receive treatment as usual (TAU) in the Early Intervention Service (n=14). Afterward, patients will switch arms to receive alternative intervention.

The intervention will consist of a computerized CRT through Neuropersonal Trainer software (Fernandez-Gonzalo et al. 2015). This includes two rehabilitation modules: 1) the Cognition Module, that addresses the following cognitive domains: on sustained, selective and divided attention; verbal, spatial, visual and working memory; and executive functions including inhibition, sequence and planning; and 2) the Social Cognition Module, which allows working different aspects of emotional processing, the theory of mind and cognitive biases through 43 multimedia-based tasks. Both modules have different levels of complexity. Each CRT session will be individualized to the cognitive needs of each patient by an expert neuropsychologist. The professional can adjust the difficulty level in each treatment session based on the participant baseline cognitive profile and his/her task performance in previous treatment sessions. The neuropsychologist will be guiding the sessions, assuring the understanding of the different tasks, and individually coaching every patient to achieve the correct performance.