Brain Health and Exercise in Schizophrenia (PEHP)

Brain Health: Effects of Exercise on Hippocampal Volume and Memory Deficits in Persons With Schizophrenia

To determine the effects of aerobic exercise on hippocampal volumes and severity of psychotic symptoms in a population of psychosis patients compared to healthy age/gender matched volunteers. Psychosis patients often suffer from a number of cognitive difficulties, including poor memory function, poor problem-solving capacity and difficulties with attention and concentration. Poor fitness and associated neurovascular deficits may arise from various sources, including poor mental health, adverse side effects of antipsychotic medications and independent cardiovascular deficits that may be due to neurodevelopmental abnormalities in patients with schizophrenia. These factors are likely contributing to markedly increased stroke risk and early mortality. These problems are not well addressed by current clinical treatments, nor is neurovascular stroke risk readily or accurately detected in clinic.In contrast, evidence from aging research strongly suggests that increased cardiovascular fitness may provide numerous cognitive benefits by promoting brain growth, particularly in the frontal lobes and the hippocampi, while reducing the risk of stroke. The current study will measure the effects of aerobic exercise on brain volumes in a population of chronic psychosis patients to determine if 1) hippocampal volumes increase in response to exercise and 2) if parallel improvements in cognitive functioning occur. Additionally, baseline and follow-up stroke risk will be assessed using a novel non-invasive approach of retinal imaging to determine the presence of underlying neurovascular pathology.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizoaffective Disorder; Poor Memory

Detailed Description

This is a 12-week, randomized trial with two parallel groups. Throughout the trial, subjects will be treated on their prescribed dose of medication. Once informed consent is obtained, subjects and healthy volunteers will be randomly assigned to either an aerobic or a resistance exercise program (N = 30 per diagnostic group in each of two exercise conditions). Patients will continue to receive their antipsychotics and other prescribed medications. Healthy volunteer data will be used to establish normal exercise-induced neuroplasticity in a non-psychiatric, non-medicated population and to establish differences in retinal vessel integrity between patients and healthy volunteers. All training will be conducted at the UBC Hospital and at dedicated exercise training facilities at the University of British Columbia. All fitness assessments (based on the initial 6-minute walk test) and exercise sessions will be monitored by trained research assistants (RAs) under the guidance of the Canadian Society for Exercise Physiology-Certified Exercise Physiologists (CSEP-CEPs). The RAs will receive pre-study exercise training from the CSEP-CEPs. During the course of the study, the training intensity will be changed according to the individual participant's response and needs via the CSEP-CEPs and RAs.

Clinical data (current medications, current diagnoses, symptom profiles, resting heart rate, blood pressure, weight) will be collected on the hospital wards at baseline and follow-up. Neuroimaging and retinal imaging will be ascertained at the UBC MRI Research Centre at baseline and follow-up. Concurrent baseline assessments of executive functioning, memory capacity and crystallized IQ will be performed at baseline. Cognitive measures, excluding IQ, will be re-assessed at follow-up. Follow-up measures will only be collected in cases were patients are still available and willing to participate in study activities.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Donna J Lang, PhD; Phone Number: 4727 604-875-2000; Email: donna.lang@ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • Recruiting
      • UBC Hospital
      • Contact: Ava Grier, BSc; Phone Number: 7053444449; Email: avagrier@student.ubc.ca
      • Contact: Donna J Lang, PhD; Phone Number: 4727 604-875-2000; Email: dlang@interchange.ubc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Sixty in-patients with chronic schizophrenia will be recruited at UBC Hospital and 60 age and gender-matched healthy (asymptomatic) community volunteers will be recruited through local community paper advertisements or posters at local community centres.

Description

Inclusion Criteria:

• Age 18 to 45 years
• Able to provide written, informed consent in English
• Patients may be on prescribed medications
• DSM-IV diagnosis of schizophrenia or schizoaffective disorder
• Normal visual acuity (or normal visual acuity achievable with corrective lenses)
• Physical ability to be engaged in a regular exercise program

Exclusion Criteria:

• A history of organic disorders (dementia, severe head injury, or developmental disorders such as autism, mental retardation, Down's Syndrome)
• A current DSM-IV diagnosis of substance dependence (during prior 12 months, excluding tobacco)
• Any history of DSM-IV diagnoses (Axis I) for other psychiatric disorders
• History of angina, heart attack or transient ischemic attacks
• Non-independent mobility or limb prostheses
• A history of severe head injury leading to loss of consciousness for > 5 minutes
• Contra-indications for neuroimaging (metal implants, non-removable orthodontic devices, severe claustrophobia, pregnancy, or surgeries within the previous 6 months)
• Currently already enrolled in a regular exercise program

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase hippocampal volume with aerobic training in schizophrenic and healthy volunteers.	Hippocampal volumes will be measured from structural MRI scans. T1-weighted 3D SPGR (spoiled gradient recalled) and high-resilution T2- weighted structural images will be obtained for the purposes of volumetric assessment of the hippocampi and the whole brain	Base-line, 8 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increases in hippocampal volumes will be positively associated with improvements in working memory performance in schizophrenia.	The Hopkins Verbal Learning Test (HVLT), will be used to assess memory function. Multiple versions of the HVLT exist (12) so practice effects will be minimized. The Rey-Osterrieth Complex Figure Test (ROCF), in which subjects are asked to reproduce a complex line drawing from memory, will be used to assess attention and working memory.	Baseline, Week 4, 8 and 12.

Collaborators and Investigators

• Sponsor: BC Mental Health and Addictions Research Institute
• Collaborators: University of British Columbia; Canadian Institutes of Health Research (CIHR); Simon Fraser University
• Investigators: Principal Investigator: Donna J Lang, PhD, University of British Columbia, Dept. of Radiology; Study Chair: William G Honer, Professor, University of British Columbia, Dept of Psychiatry; Study Chair: Allen Thornton, Unspecified, Simon Fraser University; Study Chair: Darren Warburton, Ass. Prof, University of British Columbia, Dept. of Human Kinetics; Study Chair: Alexandra T Vertinsky, Clin. Instr., University of British Columbia, Dept. of Radiology; Study Chair: Alexander Rauscher, Ass. Prof., University of British Columbia, Dept. of Radiology

Publications and helpful links

General Publications

• Woodward ML, Gicas KM, Warburton DE, White RF, Rauscher A, Leonova O, Su W, Smith GN, Thornton AE, Vertinsky AT, Phillips AA, Goghari VM, Honer WG, Lang DJ. Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia. Schizophr Res. 2018 Dec;202:158-165. doi: 10.1016/j.schres.2018.06.054. Epub 2018 Jun 29.
• Kim DD, Lang DJ, Warburton DER, Woodward ML, White RF, Barr AM, Honer WG, Procyshyn RM. Heart-rate response to alpha2-adrenergic receptor antagonism by antipsychotics. Clin Auton Res. 2017 Dec;27(6):407-410. doi: 10.1007/s10286-017-0444-4. Epub 2017 Jul 3.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: June 21, 2011
• First Submitted That Met QC Criteria: July 12, 2011
• First Posted (Estimated): July 13, 2011

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Schizophrenia; Mental Health; Schizoaffective Disorder; Brain Health; Poor memory
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: 231233-BSB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED