Aerobic Exercise for the Improvement of Cognition and Enhancement of Recovery in Post-acute Schizophrenia

As part of the measurement of cognitive performance during the screening phase and at the main measurement times (at baseline, day 98, day 182 and day 365), patients and control subjects will be tested using the Verbal Learning and Memory Test (VLMT).

As part of the measurement of cognitive performance during the screening phase and at the main measurement times (at baseline, day 98, day 182 and day 365), patients and control subjects will be tested using a test of verbal declarative episodic memory, the Digit Symbol Substitution Test (DSST).

As part of the measurement of cognitive performance during the screening phase and at the main measurement times (at baseline, day 98, day 182 and day 365), patients and control subjects will be tested using the Trail Making Test A and B (TMT) as a test of executive functions, quick visual comprehension, attention, and processing speed.

The partial aspect of verbal fluid from the letter Cognitive Assessment Tool for Schizophrenia (B-CATS) is also used in the neuropsychological investigation at the main measurement times (at baseline, day 98, day 182 and day 365).

As part of the measurement of cognitive performance during the screening phase and at the main measurement times (at baseline, day 98, day 182 and day 365), patients and control subjects will be tested using the Facial Affect Recognition (AOP) and Theory of Mind methods. These are tasks using the Movie for the Assessment of Social Cognition (MASC).

The assessment of psychopathology on the basis of a patient interview takes place at all main measurement times. At baseline, day 98, 182 and day 365. The PANSS uses a standard procedure for assessing schizophrenia symptoms, which measures the severity of individual symptoms as well as the various symptom subgroups of positive and negative symptoms and general psychopathology.

The Clinical Global Impression Scale (CGI) assesses the overall symptom severity and response to interventions or therapies for psychiatric conditions to assess the effectiveness of the measures applied. It will be called up 9 times from baseline up to 12 months: At baseline, day 14, 68, 98, 140, 182, 196, 273 and day 365.

The Social and Occupational Functioning Assessment Scale (SOFAS) estimates social and professional performance. It will be called up 9 times from baseline up to 12 months: At baseline, day 14, 68, 98, 140, 182, 196, 273 and day 365.

The Social Assessment of Functioning Scale (GAF) also estimates social and professional performance. It takes place at all main measurement times. At baseline, day 98, 182 and day 365.

The Brief Symptom Inventory (BSI-53) records the symptoms using 53 items. It takes place at all main measurement times. At baseline, day 98, 182 and day 365.

The Calgary Depression Scale for Schizophrenia (CDSS) measures suicidality and severity of depressive symptoms. It will be called up 9 times from baseline up to 12 months: At baseline, day 14, 68, 98, 140, 182, 196, 273 and day 365.

The University of California San Diego Performance-based Skills Assessment (UPSA-B) will be used to assess the day-to-day functioning of patients with schizophrenia in the household, communications, finance, transportation, and leisure activities role play situations. It takes place at all main measurement times. At baseline, day 98, 182 and day 365.

Functional Remission of General Schizophrenia (FROGS) is used as a tool to measure changes in functional levels. It takes place at all main measurement times. At baseline, day 98, 182 and day 365.

The Personal and Social Performance Scale (PSP) is also a tool to measure changes in functional levels. It takes place at all main measurement times. At baseline, day 98, 182 and day 365.

Only at the beginning and end of the intervention, and after one year, is the World Health Organization's Quality of Life Questionnaire (WHOQOL-Bref) used to record quality of life (The WHOQOL Group, 1998).

Also, the body height (in meter) and weight (in kg) of the study participants are measured. Thereupon the BMI is calculated from the body weight (kg) divided by the square of the height (m2). The unit of BMI is kg / m2.

At four time points, just prior to initiation of V1, V4, V6 after the end of the intervention and at V9 after the follow-up period of 6 months, structural and functional MRI (fMRI) examinations are performed on a 3 Tesla whole-body MR scanner in patients and healthy control subjects (Siemens) made.

The findings are compared with data from healthy controls and non-diseased first-degree relatives of patients with schizophrenia who have been evaluated in other BMBF-funded studies ("MooDS", "IntegraMent"). In addition, cross-sectional comparisons (TAU + Exercise vs. TAU + BKGT) and progress measurements to characterize treatment effects are planned. The measurements are divided into 2 appointments to reduce the burden on patients and subjects by the measurement time.

First, structural measurements (T1 sequence, duration: approx. 5 minutes) and investigations of the fiber connections in the brain by means of diffusion-weighted imaging (DTI, duration: approx. 10 minutes) are carried out.

By means of fMRI, the tasks resting activity, working memory, episodic memory, reward processing, social perspective takeover, emotion processing as well as ability to inhibit are to be investigated with already well pre-examined tasks.

A function measurement is performed at rest without stimulation (rsMRT), which provides information on the functional networking of different brain regions at rest (duration: approx. 5 minutes). There are also three fMRI surveys that record brain activity during simple psychological tasks. - The ability to inhibit (prefrontal cortex, anterior cingulate gyrus) is examined by means of a so-called flanker task. This is to respond to a specific target stimulus, which is surrounded by either the same (congruent) or by distracting (incongruent) stimuli. - Duration: 11 minutes

As part of the sports medical stress test, the determination of endurance performance in patients and control subjects takes place. For this examination, like in training, finder bike use and measurements of heart rate, lactate concentration and exertion sensation are performed. The ergometry is carried out as a Vita maxima examination, so it ends when the subjects can not or do not want to keep pedaling or when the termination criteria according to Steinacker \& Liu (2002) occur. From the examination, various submaximal and maximal parameters can be determined, have the validity for endurance performance and the training intensity can be determined. The examination is carried out under standardized and safe conditions and after a detailed medical history and physical examination to exclude contraindications.

Activity meters are used to control the physical activity of study participants outside the study intervention.

Also, the attitude of the study participants to therapy and medication is recorded. For this, the Drug Attitude Inventory (DAI) is used. Is takes place at the main measurement times (at baseline, day 98, day 182 and day 365).

The Service Engagement Scale (SES), which assesses accessibility, cooperation, help seeking and adherence, is used. It takes place at the main measurement times (at baseline, day 98, day 182 and day 365).

The laboratory diagnostic measures include a laboratory blood test, with evaluation of blood lipid levels, the C-reactive protein, glycohemoglobin (HBA1c). It takes place at the main measurement times (at baseline, day 98, day 182 and day 365).

Examination of the urine at baseline excludes pregnancy and drug abuse.

Investigation of gene expression takes place at baseline.

Investigation of genome-wide epigenetics takes place at the main measurement times (at baseline, day 98, day 182 and day 365).

Investigation of proteomics at the main measurement times (at baseline, day 98, day 182 and day 365).

Investigation of BDNF levels at the main measurement times (at baseline, day 98, day 182 and day 365).