Cognitive Remediation Therapy in Schizophrenia: Effects on BDNF Levels

The main objective of the study is to analyse the role of a neurotrophic factor (BDNF) as a putative biological marker of the cognitive recovery in schizophrenia following a Cognitive Remediation Therapy (CRT). Additionally, the role as outcome predictors of BDNF serum levels and the Val66met polymorphism and data from functional and structural neuroimaging will be studied.

Forty patients with schizophrenia disorder and twenty healthy volunteers will be recruited. Patients will be randomly allocated either the experimental group, undergoing an individual CRT for 40 hours during 16 weeks, or the control group following a psycho-educational intervention without any neurocognitive work, both lasting the same amount of hours and period of time. Blood samples will be obtained from participants in four moments: before treatment, at week 4, at week 16, and at 32 week follow-up. In addition, repeated measurements will be obtained with a neurocognitive battery based on the MATRICS consensus battery and the Positive And Negative Syndromes Scale (PANSS). Assessments will be conducted by trained personnel who will remain blind to the group assignment. A factorial model will be performed conducting a repeated measures analysis of covariance (ANCOVA) to study the effects of CRT on the levels of BDNF, neurocognition, symptoms and social functioning, adding the necessary co-variants. Finally, a linear regression model to determine the predictive role of serum levels of BDNF and data from functional and structural neuroimaging on the effects of CRT will be performed.

The program has a duration of 40 sessions (one hour of duration), with two sessions for week during four months. It is carried out individually and utilizes paper and pencil tasks. The main technique utilized is the scaffolding (to provide strategies when the patient cannot carry out the task and to withdraw him when he is yet able of doing it alone) in a context of learning without errors.

The program has a duration of 40 sessions (one hour of duration), with two sessions for week during four months. It is carried out individually and utilizes teaching information and coping skills and neuropsychological issues are not addressed.

Change Measurements of serum BDNF levels will be carried out by personnel blind to subjects' group assignment. Platelet and serum samples will be diluted with diluent included in the R&D Human BDNF Quantikine Enzym Linked Immunosorbent Assay (ELISA) kit (Yasuhito et al. 1987).

Inclusion Criteria: Diagnosis of schizophrenia according to DSM-IV-TR and confirmed by the semi-structured interview (SCID) for the axis 1. Presence of cognitive deficit confirmed by the neuropsychological battery Stable symptomatology at least during the last six months and the estimation of not modifying pharmacological antipsychotic treatment. Exclusion Criteria: Presence of organic-cerebral affectation due to neurological or traumatic conditions Abuse of psychotropic substances Presence of other psychiatric symptomatology

Penades R, Segura B, Inguanzo A, Garcia-Rizo C, Catalan R, Masana G, Bernardo M, Junque C. Cognitive remediation and brain connectivity: A resting-state fMRI study in patients with schizophrenia. Psychiatry Res Neuroimaging. 2020 Sep 30;303:111140. doi: 10.1016/j.pscychresns.2020.111140. Epub 2020 Jul 15.