The effects of mindful exercise on cognition in patients with schizophrenia: A systematic review and meta-analysis of randomized controlled trials

Cognitive impairment is a core symptom of schizophrenia. This study investigated the effects of mindful exercise on the cognitive performance of individuals with schizophrenia. A systematic review and meta-analysis were performed from inception to March 2023. The quality of included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. A random effects model was used to generate the pooled effect size. Ten randomized controlled trials met the inclusion criteria with fair-to-good methodological quality. The results showed that Mindful exercise significantly improved global cognition in patients with schizophrenia ( g = 0.25, p = .002). There was a significant difference in mindful exercise compared with the passive control group ( g = 0.34, p = .002), whereas no significant difference was found between the mindful exercise and exercise intervention group ( g = 0.09, p = .371). These findings indicate that mindful exercise could be promising for improving cognition in patients with schizophrenia.


Introduction
Cognitive impairment is a core symptom of schizophrenia (Green et al., 2000), which manifests as a range of one to two standard deviations below the general population, becomes apparent in various domains from the onset of illness, and endures over time (Hoff et al., 1999).These cognitive impairments lead to long-term disabilities and significantly affect functional performance (Green et al., 2000;Green et al., 2004).Pharmacological treatments significantly affect psychotic symptoms; however, their effectiveness in addressing cognitive impairment is limited (Fusar-Poli et al., 2015).Recent clinical treatment guidelines have mentioned the benefits of non-pharmacological treatments such as cognitive remediation therapy and aerobic exercise in improving cognitive impairment in patients with schizophrenia (Vita et al., 2022).However, the impact of cognitive remediation and aerobic exercise on cognitive function in individuals with schizophrenia exhibited minimal effect sizes (Cohen's d = 0.21to 0.29) (Shimada et al., 2022;Vita et al., 2021).Seeking alternative treatment approaches to improve cognitive function in schizophrenia is the aim of the present research.
Recent evidence suggests that physical exercise can serve as an adjunct treatment to medications (Vancampfort et al., 2019).Several studies have reported that exercise can improve psychiatric symptoms in addition to physical and mental health in patients with schizophrenia (Dauwan et al., 2016;Firth et al., 2015).In addition, increased levels of aerobic exercise can have a small to moderate effect on global cognition in patients with schizophrenia (Firth et al., 2017).
An updated meta-analysis of 15 clinical trials also indicated that aerobic exercise has small-to-moderate effects on global cognition, attention, working memory, and verbal learning in patients with schizophrenia, recommending group aerobic exercise supervised by trained personnel for >90 min per week for at least 12 weeks to improve cognitive performance (Shimada et al., 2022).However, patients with schizophrenia encounter obstacles in engaging in physical activity due to illness, including fatigue, impaired motor control and coordination, and a lack of motivation (Fogarty and Happell, 2005).In a meta-analysis, approximately one-third of participants with schizophrenia discontinued their exercise regimen during the intervention period (Dauwan et al., 2016).Therefore, there is an urgent need to formulate pragmatic regimens of physical activities in this population.
Mindful exercises such as yoga, qigong, and tai chi emphasize the attainment of wellness through symmetrical physical postures, internal awareness, deep breathing (Gendron et al., 2018).These exercises, commonly practiced in Asian cultures, require coordinated mind-body interactions that are executed in a harmonious manner (Zheng et al., 2018).In investigations related to schizophrenia, research has indicated that patients prefer physical activities characterized by low intensity, self-directed engagement, and the ability to proceed at their own time and pace, along with social support (Tew et al., 2023).Therefore, mindful exercise may align with these features and could be suitable for individuals with schizophrenia.
Plausible mechanisms that account for the potential benefits of mindful exercise should be considered from several perspectives.Firstly, mindful exercises such as baduanjin and tai chi are classified as light-tomoderate aerobic exercises (An et al., 2008;Lan et al., 2008).Prior research indicated that aerobic exercise had small effects on global cognition in schizophrenia (Shimada et al., 2022).Biomechanical, physiological, and psychological changes engendered by aerobic exercise in individuals with schizophrenia can all be achieved through mindful exercises.Second, mindful exercises require individuals to simultaneously focus on the coordination of movements and the regulation of energy/breath (Chen et al., 2016;Wayne et al., 2015), which can impose significant cognitive demands.This demand for practicing mindful exercises has been indicated to have a favorable impact on cognitive function (Wayne et al., 2015).Third, the emphasis on the integration of breathing into rhythmic movements may lead to the downward regulation of the hypothalamic-pituitary-adrenal axis.Recent study has reported increased activation in hypothalamicpituitary-adrenal axis is associated with poor cognitive performance in patients with psychosis (Cherian et al., 2019;Labad et al., 2016).The beneficial effect of mindful exercise might consequently alleviate stress and depression, and enhancing cardiovascular function (Li et al., 2018) and thus leading to better cognitive performance in patients with schizophrenia.
Several recent meta-analyses have shown that mindful exercise may significantly improve positive symptoms (Li et al., 2018;Wei et al., 2020) and reduce negative symptoms (Li et al., 2018;Sabe et al., 2019;Wei et al., 2020;Zheng et al., 2016) and depression (Wei et al., 2020).Previous meta-analyses have also provided evidence supporting mindful exercise for improving quality of life among patients with schizophrenia (Cramer et al., 2013); however, a more recent meta-analysis enrolling 323 participants revealed a non-significant effect on quality of life in patients with schizophrenia as compared to standard treatments (Wei et al., 2020).
For cognitive functions, previous review encompassed 4 randomized controlled trials, indicated inconsistent results regarding the effects of mindful exercise versus non-mindful exercise on working memory in patients with schizophrenia; moreover, no significant difference was found in attention (Li et al., 2018).A more recent meta-analysis that included both randomized and non-randomized controlled trials, totaling 132 participants, found no significant effect of mindful exercise on global cognition in schizophrenia compared with treatment as usual (Wei et al., 2020).This study was inconclusive since non-randomized study designs are prone to confounds thus leading to limitations in study validity (Andrade, 2021).Nevertheless, the authors rated the quality of evidence on cognition relatively low (Wei et al., 2020).Metaanalyses investigating the effects of mindful exercise on cognition in schizophrenia have yet to provide conclusive results owing to insufficient data and methodological issues (Li et al., 2018;Wei et al., 2020).Research is needed to determine the effects of mindful exercise compared with different control interventions, and further metaanalytic reviews are needed to include more recent studies of mindful exercise in schizophrenia for analyses.
We conducted a meta-analysis to evaluate the effects of mindful exercise on cognitive function in patients with schizophrenia.This study also investigated the influence of patient and intervention characteristics on the intervention outcomes using subgroup analysis and metaregression.

Search strategy
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Moher et al., 2009).Two authors (CCR and LYW) independently performed a literature search of the following databases from inception to March 2023: PubMed, Embase, Cochrane Library, and the Cumulative Index of Nursing and Allied Health (CINAHL).The search terms were as follows: (schizophrenia OR schizophrenia [MeSH] OR schizophrenic OR psychosis OR "severe mental illness") and (mind-body OR mindful OR yoga OR yogic OR tai chi OR taiji [MeSH] OR qigong OR baduanjin OR wuqinxi OR pilates) and (cognitive function OR cognition).A manual search of reference lists was performed to identify any additional studies.

Inclusion criteria
The inclusion criteria were: (1) randomized controlled trials published in peer-reviewed journals; (2) the intervention group comprising at least one type of mindful exercise, such as tai chi, qigong, or yoga, (3) participants in the control group were passive controls or exercise interventions.A passive control were participants received treatment as usual, were instructed to maintain their usual lifestyle or waitlist control.The exercise interventions were participants engaged in dosematched aerobic exercise or combined exercise (such as combined aerobic exercise with resistance exercise); and (4) the study participants were diagnosed with schizophrenia and were older than 18 years.We included studies published in English.

Methodological quality assessment
We evaluated the methodological rigor using the Physiotherapy Evidence Database (PEDro).The PEDro scale comprises 11 items, including: (1) specification of the eligibility criteria; (2) random allocation of participants; (3) concealed allocation; (4) baseline   (Foley et al., 2003), a PEDro total score ranging from 9 to 10 was classified as excellent, scores from 6 to 8 were deemed good, scores from 4 to 5 were considered fair, and scores lower than 4 were regarded as poor.Two authors (CCR and LYW) conducted the assessments independently.Discrepancies were resolved through discussions.

Data extraction
Two independent reviewers (CCR and CTT) used predeveloped data extraction forms to retrieve all relevant information, including participant characteristics, details of the intervention, and outcome measures.The primary outcome was global cognition, which was operationally defined as the mean change in all cognitive outcome measures from preto post-test.When multiple cognitive domains were assessed, a composite global cognition score was derived by averaging the change in the scores of each domain (McGurk et al., 2007;Shimada et al., 2022;Wykes et al., 2011).The secondary outcome was acceptability, which was defined as the percentage of participants who discontinued the study before study completion.

Statistical analysis
A random-effects model was applied to calculate Hedge's g and 95 % confidence intervals (CIs) for primary outcome.According to Cohen's (1992) guidelines, the effect sizes were categorized as small (0.2), medium (0.5), or large (0.8).The secondary outcome was calculated using odds ratios (OR) and 95 % CI with reference to mindful exercise group.We conducted subgroup analyses to investigate the effects of mindful exercise compared to different types of exercise, such as aerobic exercise alone or combined aerobic exercise with resistance exercise.We also conducted meta-regression analyses to assess the impact of methodological rating, age of participants, intervention length, and weekly amount of practice on the effects of mindful exercise.We also performed a sensitivity analysis by individually removing the included articles one at a time to assess the impact of each study on the obtained results.I 2 was used to assess the heterogeneity of the included studies.I 2 values of 25 %, 50 %, and 75 % corresponded to low, moderate, and high heterogeneity, respectively.All statistical analyses were conducted using the Comprehensive Meta-analysis 4 software.

Search results and participant details
Studies of 10 journal articles were eligible for inclusion.The details of the search results and reasons for exclusion are summarized in Fig. 1.The study characteristics and intervention details are presented in Table 1.Five studies were conducted in China, 4 in India, and 1 in Taiwan.Regarding participant recruitment settings, five studies recruited participants from outpatient settings, three from inpatient settings, and two from both outpatient and inpatient settings.The analysis included 909 participants: 376 were assigned to receive mindful exercise and 533 to receive control conditions.Among the control conditions, 313 participants were assigned to passive control group, 220 were assigned to aerobic exercise group.The mean age was 39.8 years (range = 23.8-55.0years).
The mindful exercise program lasted 55 min on average per session (range = 40-60 min), four sessions per week (range = 1-7 sessions), and lasted for an average of 10 weeks (range = 3-24 weeks).The overall duration of the intervention was 30.5 h (range = 15-80 h).In these studies, six trials used yoga (Behere et al., 2011;Bhatia et al., 2022;Bhatia et al., 2017;Govindaraj et al., 2021;Jayaram et al., 2013;Lin et al., 2015), two used baduanjin (Chen et al., 2022;Li et al., 2020), one used tai chi (Ho et al., 2016), and one used yijinjing (Gao et al., 2021).The descriptions of these mindful exercise were presented in Table 2.For comparison, 5 studies adopted a 3-group comparison design.Among them, four studies included all groups in the analysis (Behere et al., 2011;Bhatia et al., 2017;Ho et al., 2016;Lin et al., 2015), whereas one study included only the mindful exercise group and the control group (treatment as usual) in the analysis, we excluded the group which mindful meditation was added to mindful exercise thus leading to unmatched dose of intervention.(Bhatia et al., 2022).Six studies used an exercise control group, five studies applied aerobic exercise (Behere et al., 2011;Bhatia et al., 2017;Chen et al., 2022;Li et al., 2020;Lin et al., 2015), and one combined aerobic exercise and resistance training (Ho et al., 2016).Among these aerobic exercise groups, all exercise interventions were implemented by certified coaches, qualified instructors, or trained mental health professionals following a group format (Table 1).The intensity of aerobic exercise was monitored in 4 of the included studies (Bhatia et al., 2017;Chen et al., 2022;Ho et al., 2016;Lin et al., 2015).

Quality assessment
The average score on the PEDro scale was 6.3 (range = 4-8 points).This result indicated that the included studies were of fair-to-good methodological quality (Table 3).All studies provided detailed descriptions of the inclusion criteria, detailed information on randomization procedures, and baseline comparability.

Factors associated with intervention effect
In the subgroup analysis of different control conditions, no significant was found between the mindful exercise aerobic exercise alone (Number of studies =5, total sample size =331, g = 0.12, 95 % CI = − 0.10 to 0.35, p = .292).There was no significant difference between mindful exercise and combined exercise (Number of studies =1, total sample size =77, g = − 0.30, 95 % CI = − 0.50 to 0.44, p = .902).
Meta-regression analysis revealed no significant correlation between the age of the participants and the pooled effect size (p = .77).There were no significant associations between the intervention factors and the methodological rating (p > .10 for all).Sensitivity analysis revealed no change in the overall results after individually removing the included studies one at a time.

Discussion
This meta-analysis investigated the effects of mindful exercises on cognitive function in individuals with schizophrenia.The pooled effect sizes across all cognitive outcomes indicated that mindful exercises had a positive effect on global cognition compared to the control conditions.The pooled effect size g was 0.25 across studies.The results revealed that mindful exercise was superior to standard treatment in improving  cognitive performance (g = 0.34).This review found that mindful exercises were significantly better than usual care, but showed no significant difference when compared with aerobic exercise.This finding suggests that mindful exercises, compared to usual care, may be a promising therapy to enhance cognitive function in individuals with schizophrenia, with efficacy similar to that of other types of exercise.In addition, mindful exercise may be considered as a valuable alternative to exercise for improving cognitive function in individuals with schizophrenia.
Mindful exercise had a small but impressive effect on global cognition.A previous meta-analysis found that aerobic exercise had small-tomoderate effects (g = 0.41) on global cognition in people with schizophrenia (Firth et al., 2017).A recent meta-analysis also showed small effects (Cohen's d = 0.21) of aerobic exercise on global cognition (Shimada et al., 2022).Consistent with these findings, this meta-analytic review found that mindful exercises have small to moderate effects on cognitive functioning in individuals with schizophrenia.Most of the clinical trials included in the current study used group-based interventions, with nine trials implementing exercise sessions of over 90 min per week and six trials with intervention periods of at least 12 weeks.Furthermore, most of the interventions were led by professionals of mindful exercises.These intervention characteristics align with the core elements of effective aerobic exercise interventions for cognitive functioning in patients with schizophrenia identified in recent studies (Shimada et al., 2022).
This study analyzed the acceptability of mindful exercise compared to aerobic exercise or passive control conditions.Although the results revealed a lower odds ratio toward mindful exercise on discontinuing the exercise regimen, the results were not statistically significant.Previous research indicated that providing professional support to help patients with severe mental illness may overcome barriers to physical activity participation (Firth et al., 2016).In the current study, both The items of PEDro scale are:   mindful and aerobic exercises were led by trained professionals, which might have enhanced the acceptability of the exercise regimen.Mindful exercise may be a feasible alternative to aerobic exercise and may complement with various exercise regimens.This provided support for the idea that mindful exercise, when conducted with professional guidance, may be a feasible alternative to aerobic exercise.Recent studies have found that combining aerobic exercise with cognitive remediation can enhance cognitive functioning in first-episode psychosis (Nuechterlein et al., 2023) and individuals with schizophrenia (Deste et al., 2023).Future research on mindful exercise could also explore the applications mentioned above.This study had some limitations.Research on the effects of mindbody exercises on cognitive function in patients with schizophrenia is at an early stage.In the current meta-analysis, only 10 research reports with 909 subjects were included for overall analysis, for head to head comparisons, only 6 to 8 studies were included, which may have led to an inconclusive results regarding the effects of mindful exercise on cognition.Moreover, the current study had limited power to compare the benefits of different types of mindful exercise (e.g., yoga, tai-chi, and Baduanjin) and control interventions.Furthermore, as only a few studies reported on the outcomes of specific domains of cognition, the effect of mindful exercise on specific aspects of cognition in schizophrenia awaits further scrutiny.Another limitation of the current study was the absence of psychosocial functioning as an outcome measure.A recent review has indicated that physical exercise is efficacious in enhancing overall functioning, social functioning, and daily life function in patients with schizophrenia (Korman et al., 2023).There is a need for comparative efficacy research that compares the benefits of mindful exercise and other intervention (e.g., brisk walking) based on a larger sample.Notably, some of the studies included in the meta-analysis had methodological limitations.Four studies did not implement assessor blindness and are thus at risk of detection bias.As such, further studies are warranted to address the gaps in research.Although we conducted a systematic search, we did not include gray literature.Furthermore, only studies published in English were included.Publication bias should be considered when interpreting results of this meta-analytic review.
The potential influence of cultural contexts warrants further consideration.Previous studies on mindfulness therapies were primarily conducted in Asian countries (Vancampfort et al., 2021).In our present research, all studies included for analysis were published by Asian authors (see Table 1).Whether the findings of this study can be generalized to Western cultures remains unclear.Studies on mindful exercises outside Asian countries are needed to validate our findings.Future research should investigate the moderating effects of patient characteristics, such as age, previous experience with mindful exercise, medication usage, and psychiatric symptoms.In addition, the intervention characteristics of mindful exercises (e.g., intensity and frequency) warrant consideration based on a larger body of literature.Moreover, future studies should examine the effect of mind-body exercise on various cognitive domains in individuals with schizophrenia, such as attention, memory, information processing speed, and executive function.
In conclusion, our study presents a comprehensive review of the effects of mindful exercise on the cognitive function in individuals with schizophrenia.These findings indicate a noteworthy enhancement in global cognitive performance after mindful exercise.Furthermore, mindful exercises demonstrated superiority over standard treatments  and exhibited effects similar to those of other forms of exercise.Subsequent research should identify key components of mindful exercises that may contribute to cognitive enhancement in individuals with schizophrenia.

Fig. 2 .
Fig. 2. Meta-analysis of mindful exercise vs control group on global cognition in schizophrenia.

Fig. 3 .
Fig. 3. Meta-analysis of mindful exercise vs aerobic exercise on global cognition in schizophrenia.

Fig. 4 .
Fig. 4. Meta-analysis of mindful exercise vs treatment as usual on global cognition in schizophrenia.

Table 1
Details of included studies.

Table 2
Descriptions of mindful exercise.

Table 3
Evaluation of methodological quality according to the PEDro scale.

Table 4
Meta-analysis of mindful exercise in people with schizophrenia.