Brain Image Markers Associated With Cognitive Training and Aerobic Exercise in Schizophrenia

This study evaluates the brain correlates of Cognitive Training and Aerobic Exercise in schizophrenia. A third of participants will receive Cognitive Training plus Standard Care for schizophrenia. Another third of participants will receive Aerobic Exercise Training plus Standard Care for schizophrenia. A control group will of participants will receive Standard Care plus Occupational Activities for the same duration and frequency as the experimental groups.

This study, randomized, open, controlled with schizophrenia-standard-care, is aimed to determine structural and functional brain changes associated to cognitive remediation and physical exercise in schizophrenia.

The study participants will be enrolled in the catchment area of the Hospital Psiquiatrico de Alava, in the province of Alava, Basque Region, Northern Spain.147 patients diagnosed with schizophrenia will be randomly assigned to Cognitive Training Group or Aerobic Exercise Group or a Control Group for a five-month period.

Both Cognitive Training Group patients and Aerobic Exercise Group patients will participate in training sessions of 60 min/d, 3 d/wk. Patients assigned to Control Group will receive the standard care for schizophrenia in this area plus occupational activities for the same duration and frequency than the two experimental groups.

Cognitive Training will be implemented through REHACOP, a cognitive remediation program for Spanish speaking patients with schizophrenia whose efficacy on cognitive performance and negative symptoms has already been demonstrated in patients with schizophrenia. REHACOP is a "paper \& pencil" based cognitive remediation program that covers 8 cognitive domains including social cognition. It is based on the principles of Optimization, Restauration \& Compensation.

Aerobic Exercise Training will consist of an intensive physical exercise program supervised by certified graduates and doctorate students of Physical Activity and Sport Sciences. Sessions will include 10-minute warming-up and 10-minute back exercises and stretches. The main part of the session will consist of aerobic exercise (20-minute indoor bicycle) and muscle-resistance and strength exercises for 20 minutes. The intensity of the sessions will be determined on a case by case basis according to the HR necessary to achieve the intensity ranges (R2-moderate and R3-high). During the sessions, the bicycle's power and pace will be individually adjusted to achieve the selected HR.

The assessment batteries, neuroimaging and Serum BDNF levels will be administered and determined at baseline and immediately following the completion of the Cognitive Remediation or Aerobic Exercise interventions.

Primary outcomes: Structural and functional brain changes will be assessed by MRI neuroimaging. A Philips Achieva 3.0T MRI system equipped with a modular 32-channel architecture. 3 different types of images will be acquired: a) T1-weighted MRI imaging, b) Diffusion Tensor imaging, c) fMRI imaging at rest and using a cognitive paradigm.

Secondary outcomes will be changes in cognitive performance, clinical and functional changes and Serum BDNF changes.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of Schizophrenia (DSM-5 F20.9)
* More than 2 years since the onset of the disease.
* Stable cognitive impairment.
* Moderate severity of cognitive impairment in MATRICS scores (T score \< 40 in, at least, 1 out of 7 cognitive domains).

Exclusion Criteria:

* Subjects clinically unstable (PANSS positive score \> 19).
* Cognitive impairment due to another medical condition (neurocognitive disorders, brain injury, intellectual disability, etc.)