Schizophrenia is associated with cognitive impairment, and treatment of cognitive dysfunction in these patients represents an area of unmet need. What is the role of exercise?
Cognitive impairments are a core symptom in patients with schizophrenia that can adversely affect treatment response and functional outcomes.1 Presently, there is limited evidence for significant pro-cognitive effects for antipsychotics and other pharmacologic approaches.2 Therefore, treatment of cognitive impairment in schizophrenia represents a tremendous area of unmet need.
Regarding non-pharmacological treatments, there has been significant research on the effects of exercise on brain structure and functional performance.3 A meta-analysis found that aerobic exercise exerted a positive effect on global cognition and some cognitive domains, but not others, in patients with schizophrenia, but findings are limited by small samples, as well as variable types and intensity of exercise and study designs.4
Huang and colleagues5 performed a 12-week randomized controlled trial of the effects of aerobic walking on cognitive function in patients with schizophrenia, and whether the intensity of aerobic walking is associated with changes in cognition. Patients were randomized 1:1 based on age and sex to usual treatment with antipsychotics with or without aerobic walking. Inclusion criteria were aged 20 to 60 years, DSM-5 diagnosis of schizophrenia, stable antipsychotic dose for at least 1 month, Positive and Negative Syndrome Scale (PANSS) total score < 95, no history of major physical illness, and no physical disability that caused difficulty walking.
The aerobic walking protocol
The program comprised 150 minutes/week of outdoor walking, typically divided over 3 to 5 sessions and each with a 5-minute warm-up, followed by a 5-minute cool-down. Transportation was provided to the exercise sessions if needed. Participants wore a Fitbit to monitor heart rate and exercise intensity. Research staff supervised each participant and provided guidance based on heart rate. The patients could rest if needed. Participants were stratified into high- and low-intensity groups based on the average in-session heart rate reserve. Cognition was evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS).
Data were analyzed using intention-to-treat and per-protocol analyses. Multivariate general linear model repeated measures were used to investigate the effects of time, group, and the time x group interaction on cognition, controlling for illness duration. The authors randomized 67 patients to treatment-as-usual (TAU, n = 34) or aerobic walking (n = 33) who completed the baseline assessment. Thirty-three patients in the TAU and 31 in the aerobic walking group completed the 12-week trial.
The mean age was 42 years; mean BMI was 27; mean PANSS total score was 79; and 42% were male. Importantly, at baseline, subjects in the aerobic walking group scored approximately 0.5 standard deviations lower on global cognition than the TAU group. The mean duration of aerobic walking was 129 minutes/week. Eleven patients achieved high-intensity walking and 22 maintained low-intensity. In the entire intent-to-treat sample, the authors found a trend for a group effect for greater improvement in verbal fluency in the aerobic walking group. They also found a significant group effect on attention and processing speed in high- versus low-intensity aerobic walking.
The authors stated that theirs was the first trial of the effects of aerobic walking and exercise intensity on cognitive function in schizophrenia. The majority (> 90%) of patients completed the trial, with a mean of 3 days of exercise per week, suggesting that this intervention is feasible and acceptable to patients, and that supervision and transportation are associated with retention. Study limitations include the modest sample size (especially the high-intensity group) and relatively short study duration, as well as the inability for blinding to the intervention.
“Mrs M” is a 48-year-old Black woman with a history of chronic schizophrenia. During hospitalization for an episode of illness exacerbation, her antipsychotic medication was changed. Over the next 4 months, she gained approximately 50 lb. Mrs M declined to lower the dose of her antipsychotic or change medications because of her clinical improvement and worry about risk of another illness relapse. However, she was receptive to the recommendation for increased physical activity for weight loss. Mrs M started walking with a neighbor friend for about 30 minutes at a moderate pace at least 3 times per week. Over the next year, she lost 36 pounds. Although there were no clinically appreciable changes in her cognitive function, she reported “feeling better” as a result of her exercise regimen.
The Bottom Line
A supervised aerobic walking program involving moderate-intensity exercise is feasible and acceptable in patients with schizophrenia. Higher intensity aerobic exercise may have modest pro-cognitive effects in these patients.
Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.
1. Hoe M, Nakagami E, Green MF, Brekke JS. The causal relationships between neurocognition, social cognition and functional outcome over time in schizophrenia: a latent difference score approach. Psychol Med. 2012;42:2287–2299.
2. Harvey PD. Pharmacological cognitive enhancement in schizophrenia. Neuropsychol Rev. 2009;19:324–335.
3. Sommer IE, Kahn RS. The magic of movement; the potential of exercise to improve cognition. Schizophr Bull. 2015;41:776–778.
4. Firth J, Stubbs B, Rosenbaum S, et al. Aerobic exercise improves cognitive functioning in people with schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2017;43:546–556.
5. Huang Y-C, Hung C-F, Hsu S-T, et al. Effects of aerobic walking on cognitive function in patients with schizophrenia: a randomized controlled trial. J Psychiatr Res. 2021;134:173-180.