The effect of mind- and body-based interventions on poststroke depression and its neural mechanisms: A systematic review and meta-analysis

The effect of mind- and body-based interventions on poststroke depression and its neural mechanisms: A systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The effect of mind- and body-based interventions on poststroke depression and its neural mechanisms: A systematic review and meta-analysis Rangchun HOU, Peter Bohao YANG, Dalinda Isabel SANCHEZ VIDAÑA, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5954227/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Post-stroke depression (PSD) is recognized as the most common psychiatric disorder following a stroke, impacting the subsequent recovery and quality of life of stroke survivors. In recent years, physical activities and mindfulness have been proven to improve depression, however, it remained unknown whether those interventions were also effective in the treatment of PSD. This systematic review aims to assess the effects of mind- and body-based interventions on PSD and their underlying neural mechanisms. The systematic review (PROSPERO registration number: CRD42024514565) searched CINAHL, Cochrane, PsycINFO, PubMed, and Scopus up to March 11, 2024, focusing on English-language studies. Inclusion criteria encompassed randomized controlled trials of stroke patients with depression using validated assessment tools, targeting body-based, mind-based, or mind-body interventions, while excluding psychological or counseling interventions and passive movements. Two authors conducted data extraction with checks for accuracy, and risk of bias was assessed using the PEDro scale, which evaluates study design and methodology, yielding a maximum score of 10 points. Data extraction and risk of bias assessment were conducted by independent reviewers. A total of 68 studies were included, involving 6,825 participants, and 54 of these studies were included in the meta-analysis. The average PEDro score of 6.51 indicates good methodological quality, with combined interventions scoring highest at 7.44, highlighting variability among the studies. Meta-analysis results demonstrate that all mind- and body-based interventions have a significant impact on PSD (p < 0.05), with effect sizes as follows: all mind- and body-based interventions (n = 66, Hedges’ g = -0.572), mind-based interventions (n = 4, Hedges’ g = -0.549), body-based interventions (n = 52, Hedges’ g = -0.532), and combined interventions (n = 10, Hedges’ g = -0.805). The systematic review and meta-analysis revealed that all mind- and body-based interventions significantly improved post-stroke depression, and combined interventions are more effective than mind-based or body-based interventions alone. It is suggested to integrate additional mindfulness elements into the daily exercises of stroke survivors in clinical practice can further alleviate depressive symptoms. Health sciences/Neurology Health sciences/Neurology/Neurological disorders body-based interventions exercise mind-based interventions mindfulness post-stroke depression stroke Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction Stroke is a leading cause of death and disability worldwide, with over 12 million new strokes occurring each year and approximately 101 million stroke survivors worldwide. The impact of stroke is profound, resulting in the loss of over 143 million years of healthy life annually and a global cost exceeding US $ 721 billion, equivalent to approximately 0.66% of the global GDP [ 1 ]. Post-stroke depression (PSD) is one of the common and serious sequelae of stroke. Within two years after a stroke, the incidence of PSD ranges from 11–41%, affecting approximately one-third of stroke survivors [ 2 , 3 ]. It contributes to poor recovery, diminished quality of life, impaired functional abilities, and increased mortality rates [ 4 ]. Currently, the commonly employed approaches for treating PSD involve medication and psychological interventions. However, evidence suggests that the effectiveness of current treatments for PSD only ranges from 30–40% of all cases [ 5 ]. The exact pathophysiology of PSD remains unclear but is believed to be multifactorial, involving a combination of issues related to ischemic-induced neural damage. Single-drug treatments have yielded inconsistent results, while most proposed composite treatment regimens have failed to deliver desired outcomes, often exposing patients to numerous side effects that further compromise their health and increase the risks of other complications [ 6 ]. Psychological therapies, such as cognitive-behavioral therapy, have shown promising initial findings in improving depressive symptoms associated with PSD. However, the studies in this area have shown high heterogeneity and generally lower quality [ 2 , 7 ]. Given the current situation, future directions in PSD treatment call for an integrated approach involving both pharmacological and non-pharmacological strategies. This may include education, mental support, family support, and functional improvement. Exploring additional avenues for positive supplementation is necessary to address the complex nature of PSD [ 6 , 7 ]. Body-based interventions, as one of the conventional treatment modalities for stroke patients, have ample evidence supporting their ability to enhance motor functions and quality of life. There is increasing evidence suggesting that exercise can also improve depression in the general population [ 8 , 9 ]. However, research specifically targeting the improvement of PSD through exercise is relatively scarce, with some studies reporting positive impacts but no definitive conclusions. On the other hand, mind-based interventions present a potentially valuable alternative approach. They are simple, can be practiced independently anywhere, and are relatively inexpensive with fewer side effects compared to pharmacological treatments. There is evidence suggesting mind-based and mind-body interventions provide potential beneficial effects on depression, as well as the effective alleviation of depressive symptoms in adults with chronic physical conditions through mind-body interventions [ 10 – 12 ]. Additionally, research suggests that mind-based interventions can improve cognitive function, which is highly relevant for stroke survivors, as up to 78.7% of them experience some form of cognitive impairment in China [ 13 – 15 ]. This systematic review and meta-analysis aims to investigate the effect of mind- and body-based interventions on PSD. It also seeks to explore the neural mechanisms involved and compare the effectiveness of mind- and body-based approaches. 2. Materials and Methods 2.1. Search strategy The systematic review was carried out in accordance with PRISMA guidelines and has been registered on PROSPERO (registration number: CRD42024514565). Two independent reviewers conducted a comprehensive screening of relevant literature from multiple databases, including CINAHL (all fields, Language: English), Cochrane (all fields, Language: English), PsycINFO (no restrictions), PubMed (Randomized Controlled Trial, Clinical Trial, Language: English), and Scopus (article title, abstract, keywords, Language: English, Document type: Article). The search spanned from the inception of the databases to March 11, 2024, and included studies published in English. The search terms are detailed in Table 1 . 2.2. Study selection The inclusion criteria for the studies were as follows: (1) randomized controlled trials (RCTs), (2) inclusion of stroke patients with symptoms of depression evaluated using validated assessment tools, and (3) interventions falling into one of the following categories: body-based interventions, mind-based interventions, or mind-body-based interventions (interventions that belong to both categories). Psychological or counseling interventions were excluded as they were not considered mind-based interventions. Additionally, passive movement interventions, such as passive range of motion exercises and massage were also excluded. 2.3. Data extraction Two authors were involved in the data extraction process, conducted in Excel, with one author extracting the data and the other verifying its accuracy. Any disagreement was resolved by a third author. The data extracted from each study included study design, description of the participants, details of the intervention, outcome measures assessed, and reported results of depressive symptoms (Mean and SD). If there was missing or omitted information, data relevant to the review was requested from the authors of the included articles and included in the synthesis, provided a response was received within 14 days. 2.4. Risk of bias Two authors independently assessed the quality of reporting and risk of bias for each study using the PEDro scale. Any disagreement was resolved by a third author. 2.5. Statistical analysis The meta-analysis was conducted to compare the effect of mindfulness meditation interventions on depression symptoms with the control group. The Review Manager version 5.4 (Cochrane Collaboration) was used to perform the meta-analysis. To analyze the effect of mindfulness meditation on depression, quantitative data of depressive symptoms measured using validated scales were extracted at baseline, post-test and follow-up. Subgroup analyses were conducted to explore the long-term effects of the mindfulness meditation interventions. Considering the variability of the data, standardized mean differences (SMD) were used to generate effect sizes for the forest plot. A random effect model for meta-analysis was used [ 16 ]. Univariate meta-regression was conducted with patient demographics, such as age and gender (expressed as the percentage of male patients), clinical information including baseline depression level, and intervention details such as the total duration of the intervention, the total number of sessions, and the type of control setting. Meta-regression was performed to explore potential associations between the aforementioned variables and the weighted Hedge’s g values at the study level. Publication bias was assessed using Egger’s test. 3. Results 3.1. Study selection A total of 1702 records were retrieved from CCTR (n = 592), CINAHL (n = 123), PsycInfo (n = 149), PubMed (n = 256) and Scopus (n = 582) (Fig. 1). 520 duplicate records were excluded and the title and abstract of 1182 were screened. 1013 articles were removed after title and abstract screening. Of the remaining 169 studies, 101 papers were excluded for reasons like not being focused on stroke or depression, lacking mind-body interventions, or not meeting the criteria for RCTs. Finally, out of the 68 studies included in the systematic review, those with missing mean and standard deviation data were excluded from the meta-analysis after attempts to contact the authors for this information proved unsuccessful. As a result, the meta-analysis incorporated data from 54 studies. 3.2. Description of the studies included The studies included a total of 6825 participants, with males accounting for 70.2% of the total cohort (Table 2). Articles on combined mind and body-based interventions encompassed 893 subjects, while those focusing on mind-based interventions included 207 participants. Studies on body-based interventions comprised 5725 individuals. In terms of intervention groups, they are divided into three categories. The first category comprises three papers on mind-based interventions involving 73 participants, incorporating relaxation techniques and mindfulness practices without exercise components [17–19]. The second category, consisting of 65 papers involving 2981 participants, encompasses body-based interventions involving various activities related to the body, such as physical therapy, physical exercise, occupational therapy, and upper and lower limb activities [20–84]. The third category, comprising 11 papers with 470 participants, focuses on combined mind and body-based interventions that integrate physical activities linked to mindfulness, such as yoga and tai chi,, as well as interventions involving exercises and mindfulness practices [30, 42–44, 46, 58, 68, 70, 76, 79, 82]. Therefore, all interventions under the combined mind and body-based category also fall within the scope of body-based interventions. The comparison groups are varied and were classified as follows: 1350 participants were allocated to the exercise or rehabilitation group, 310 individuals were part of control groups involving psychological interventions, 1043 subjects received standard or usual care, 486 participants belonged to the no intervention, no treatment, waitlist, or sham intervention group, and 35 subjects were assigned to educational control groups (Table 2). Regarding the intervention sessions and their durations per session, mind-based interventions typically consisted of 8 to 20 sessions, lasting between 80 to 150 minutes per session. Body-based interventions showed a wider range, ranging from 3 to 312 sessions, with session durations varying from 10 to 210 minutes. Combined interventions spanned from 6 to 60 sessions, lasting between 40 to 210 minutes per session. Table 3 shows the depression scores at baseline, post-test, and follow up. 3.3. Risk of bias The methodological quality of the included studies was assessed using the PEDro scale. The PEDro scale consists of 11 items that evaluate aspects of study design, methodology, and statistical reporting. Each item is scored as either present (1 point) or absent (0 points), with a maximum possible score of 10 points (the first item is not included in the total score) [85]. The average PEDro score across all included studies was 6.51. Studies on mind-based interventions had an average PEDro score of 6, ranging from 4 to 7. Body-based interventions had an average PEDro score of 6.57, ranging from 4 to 8. Combined interventions had an average PEDro score of 7.44, ranging from 6 to 8 ( Table 4 ). This indicates a good overall methodological quality in the included studies and underscores the variability in methodological quality among them [85]. 3.4. Effect size According to Hedges' g values, which categorize effect sizes as small (0.15), medium (0.40), and large (0.75) [86], the meta-analysis results ( Table 5 ) indicate that mind- and body-based interventions, whether used alone or in combination, significantly reduced depressive symptoms compared to the control group (Hedges’ g = -0.572, p < 0.001, I² = 82.51%, p < 0.001, Fig. 2 ). The overall significance remained robust during the leave-one-out sensitivity analysis, showing Hedges’ g values ranging from − 0.485 to -0.584, which consistently demonstrate medium effect sizes. The meta-analysis of 30 studies that included follow-up (n = 30, Table 5 ) showed that mind- and body-based interventions, whether used alone or combined, reduced depressive symptoms from pre-test to follow-up compared to the control (Hedges’ g = -0.739, p < 0.001, I² = 89.77%, p < 0.001, Fig. 3 ). The follow-up period ranges from 3 weeks to 12 months suggesting a long-term effect of the interventions. The subgroup analysis of mind-based interventions (n = 4 Table 5 ) showed a significant reduction of depressive symptoms (Hedges’ g = -0.549, p = 0.001, I² = 0.000, p = 0.497, Fig. 4A ) compared to the control. Similarly, mind-based interventions significantly reduced depressive symptoms after the follow-up period (n = 4, Hedges’ g = -0.802, p = 0.017, I² = 71.66%, p = 0.014, Fig. 4B ) which ranged from 3 weeks to 12 months. The subgroup analysis of body-based interventions (n = 52, Table 5 ) showed a significant reduction of depressive symptoms (Hedges’ g = -0.532, p < 0.001, I² = 83.34%, p < 0.001, Fig. 5A ) compared to the control. Similarly, body-based interventions significantly reduced depressive symptoms after the follow-up period (n = 22, Hedges’ g = -0.700, p < 0.001, I² = 91.33%, p < 0.001, Fig. 5B ) which ranged from 3 weeks to 12 months. Combined mind- and body-based interventions (n = 10) significantly reduced depressive symptoms compared to the control (Hedges’ g = -0.805, p < 0.001, I² = 80.99%, p < 0.001, Fig. 6A ). Similarly, combined mind- and body-based interventions significantly reduced depressive symptoms after the follow-up period (n = 4, Hedges’ g = -0.994, p < 0.001, I² = 77.14%, p = 0.004, Fig. 6B ) which ranged from 3 weeks to 12 months. The univariate meta-regression analysis showed a negative relationship between the total duration of the intervention in hours and the effect size (p = 0.045, Fig. 7 ). 4. Discussion The study aimed to investigate and compare the effects of mind- and body-based interventions on PSD. At post-intervention and follow-up, all interventions involving mind-based, body-based, and combined approaches showed significant improvements in PSD. A negative and significant relationship was observed between the overall duration of interventions and the degree of PSD improvement. All four categories show studies with good quality (average PEDro score ≥ 6) though wherein 40% studies (2/5) with fair quality in the category of mind-based intervention and 13.85% studies (9/65) with fair quality in the category of body-based intervention [ 87 ]. Reduced methodological quality mainly results from the limitation of mind- and body-based interventions per se that are difficult for subjects and therapists blinding [ 88 ]. The result of the risk of bias assessments presents that included studies can offer reliable and valid results while being clustered into the current categories. Nevertheless, the interpretation of current results that included mind-based interventions require more caution, contrasted to results solely from the category of body-based interventions, as PEDro (designed for physiotherapy practice) may not satisfy inherent components of mindfulness like cultural context resulting in inaccurate appraisal, probably underestimated quality of study in the current review [ 89 ]. Future studies may choose an ideal assessment tool and/or set suitable thresholds for assessment results, based on included study designs, to measure the studies’ ‘real’ quality for critical appraisal and more robust interpretation of results. Studies show that engaging in physical activities can significantly improve depression, a fact well-established in both the general population and patients with depression [ 90 , 91 ]. Research reveals that depressive symptoms in stroke patients decrease right after exercise [ 92 ]. For stroke survivors, engaging in physical activities not only improves motor functions like muscle strength, range of motion, balance, and walking but also enhances cognitive abilities and levels of independence in daily activities [ 93 – 95 ]. These improvements are inversely associated with the depressive symptoms experienced by stroke [ 96 – 99 ]. Mindfulness cultivates awareness of present experiences and an attitude of non-judgmental acceptance of current experiences [ 100 ]. Mindfulness can help individuals better cope with adversity [ 101 ]. In stroke patients, mindfulness has been associated with a reduction in depressive symptoms [ 102 , 103 ]. Mindfulness interventions can adjust depression-related mediators, such as breaking patterns of rumination, and boosting resilience that acts as a protective factor against PSD [ 104 – 106 ]. Additionally, mindfulness has been found to alleviate fatigue related to neurological conditions, improve motor imagery post-stroke, and enhance cognitive performance in the general population [ 107 – 111 ]. PSD is closely linked to the brain changes that occur following a stroke, leading to the disruption of key pathways responsible for emotion regulation [ 112 ]. This disruption involves the monoamine systems, glutamatergic systems, excitotoxicity, the gut-brain axis, neuroinflammation, and abnormal neutrophil responses [ 112 , 113 ]. From a neuromechanistic perspective, both body and mind interventions can induce significant neuroplasticity [ 114 – 119 ]. In individuals with cerebral ischemia, exercise improves dendritic and axonal plasticity, promoting neural pathway reconstruction [ 120 ]. Mindfulness can have an impact on specific brain regions; practicing meditation is associated with increased neural activation in regions like the insula, frontal lobe, prefrontal cortex, and hippocampus, potentially leading to improvements in cortical thickness and brain functional connectivity [ 116 , 117 ]. Both exercise and mindfulness can regulate inflammation factors and induce the increase of neurotrophic factors like BDNF [ 121 – 123 ]. Low levels of BDNF are strongly associated with the risk of post-stroke depression [ 124 ]. Exercise also inhibits glutamate expression, and reduces brain damage. Furthermore, it is believed that meditation reduces cortisol levels top-down by altering brain regions, while the body adapts bottom-up to exercise [ 125 , 126 ]. These changes and adaptations ultimately contribute to regulating the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the gut-brain axis [ 125 , 127 , 128 ]. Together, these neurobiological mechanisms associated with exercise and mindfulness work to alleviate post-stroke neuroinflammation, aid in the reconstruction of neural pathways, and regulate emotions. The combination of interventions focusing on physical rehabilitation and mental health forms a connection between the body and mind which holds the potential to generate benefits that go beyond the mere sum of the individual interventions [ 126 ]. Those effective interventions for PSD can lead to improved mental well-being, better functions and social interactions, and enhanced overall quality of life for stroke survivors. The meta-analysis results indicate that the effectiveness of mind and body-based interventions during the follow-up period remained significant, with each intervention type showing a higher effect size at the end of follow-up compared to post-intervention. This suggests the presence of long-term effects of interventions (ranging from 3 weeks to 12 months). Animal studies indicate that animals engaging in exercise within 24 hours after a stroke exhibit improved behavioral outcomes and reduced ischemic volume [ 129 ]. It is believed by researchers that early neuroplasticity post-stroke is more robust, and early physical interventions can prevent learned overuse of the unaffected side, thereby beneficially impacting cortical reorganization, which may continue to have a positive effect on PSD [ 129 , 130 ]. Additionally, both physical and mindfulness interventions contribute to reducing the risk of post-stroke complications. Exercise can reduce the risk of muscle atrophy, pressure ulcers, and cardiovascular diseases, while interventions based on mindfulness may assist in alleviating chronic pain [ 131 – 135 ]. Both exercise and mindfulness provide patients with valuable coping mechanisms and strategies, finally improving their quality of life and alleviating PSD [ 90 , 136 ]. Mind-based interventions alone significantly reduced depressive symptoms after the intervention (Hedges’g = -0.549, Fig. 4), and this effect was sustained during the follow-up period (Hedges’g = -0.802, Fig. 4), which lasted from 3 to 12 weeks post-intervention. Mindfulness-based recovery programs for stroke survivors may not only help lower stress levels and enhance recovery behaviors but also significantly reduce post-stroke depression by fostering deeper insights and creating a supportive community throughout the recovery journey [ 137 ]. Mindfulness alleviates depression partially through emotional regulation mechanisms, particularly by enhancing cognitive reappraisal and reducing expressive suppression [ 138 ]. Emotional regulation strategies, such as reappraisal, which involve reframing the meaning of a situation, are negatively associated with depression, while expressive suppression correlates positively with depressive symptoms [ 139 , 140 ]. Mindfulness interventions promote reappraisal as a key component, leading to improved emotional outcomes [ 141 ]. Additionally, mindfulness has been linked to reduced rumination, a maladaptive thought pattern that perpetuates depression, suggesting that it may mediate the relationship between mindfulness and depressive symptoms [ 142 , 143 ]. Structural changes in brain regions have been associated with improvements in depressive symptoms through mind-based interventions [ 144 ]. Meditation practice can influence self-referential processing and enhance present-moment awareness, leading to alterations in the default mode networks, particularly the midline prefrontal cortex and posterior cingulate cortex, which are associated with self-awareness [ 145 ]. Changes in fronto-limbic networks have also been linked to attention and self-awareness, suggesting that these alterations following mindfulness practice may facilitate the treatment of depression [ 144 ]. Also, mindfulness-based interventions have been associated with increased cortical thickness in the insula and somatosensory cortex, correlating with reductions in worry, state anxiety, and depression [ 145 ]. When comparing the effect size of mind- and body-based interventions alone, the magnitude of the effect is similar (n = 4, Hedges’ g = -0.549; n = 52, Hedges’ g = -0.532, respectively) suggesting that either intervention alone may be beneficial. Interestingly, an intervention combining both mind- and body-based approaches results in an even larger effect on post-stroke depression (n = 10, Hedges’ g = -0.805). The compelling evidence of structural brain changes and enhanced self-awareness resulting from mindfulness practices underscores the transformative potential of integrating both mind- and body-based interventions to significantly alleviate post-stroke depression and improve overall well-being. Based on results from the meta-analysis, body-based interventions significantly reduce depressive symptoms compared to the control group (Fig. 5). In terms of short-term effect size (Table 5), the effect of body-based interventions (Hedges’g = -0.532) is lower than combined mind- and body-based interventions (Hedges’g = -0.805). Body-based interventions (Hedges’g = -0.532) may result in slightly less pronounced recovery from depression compared to mind-based interventions (Hedges’g = -0.549). Although the effect was smaller than mind-based and combined interventions, the effect size of body-based interventions was generated by a larger amount of studies than mind-based and combined interventions, which may indicate the results of body-based interventions may have higher reliability. Regarding the underlying mechanism of body-based intervention in reducing depression, brain plasticity may be a significant factor. Brain plasticity was deemed as changes in multiple domains, like structure rebuilding and function activating, which are abnormal in key brain regions of depression patients [ 146 ]. Evidence from an animal study showed that four weeks of treadmill aerobic exercise resulted in a significant increase in the total volume of dentate gyrus (DG) and CA1 of rats treated by chronic unpredictable stress model [ 147 ]. In addition, another review article also indicated that major depressive disorder (MDD) patients have been found to have a decreased hippocampus volume, specifically DG atrophy, whereas individuals with MDD who are on medication show normal, even greater, DG volumes when compared to those who are not currently receiving treatment for MDD [ 148 ]. Overall, the above evidence suggests that body-based interventions may reduce depressive symptoms by modulating and rebuilding brain structures, especially DG. Function activating is also involved in brain plasticity, and many studies that focused on event-related potential (ERP) showed exercise can activate brain function in depressive patients. For instance, a randomized control trial demonstrated that moderate-intensity exercise increases N2 amplitude and decreases BDI-II scores, indicating improved cognitive control and reduced depression symptoms brought by exercise [ 149 ]. Furthermore, another study also showed mediative aerobic exercise significantly increased N2 and P3 amplitudes and reduced BDI-II scores, suggesting aerobic exercise can activate cerebral cortical neuronal excitability and therefore decrease depressive symptoms [ 150 ]. In summary, body-based intervention, especially aerobic exercise, can activate brain functions to achieve favorable changes in EPR in depressed patients. Excepting the clinical implication in improving depressive symptoms, body-based interventions can also provide multidimensional benefits including motor function recovery and cognitive improvement to post-stroke depression patients [ 151 ] , [ 152 ]. According to previous evidence, a community-based study in Auckland, New Zealand that lasted one year showed that 88% of the 680 stroke patients had hemiparesis, which suggested a large proportion of stroke survivors suffered from motor function deficits [ 153 ]. In this way, in addition to improving depressive symptoms, body-based interventions, like aerobic and resistance exercise programs were also effective ways to improve motor functions [ 154 ]. Regarding cognitive functions, similarly, a clinical trial showed that the combination of aerobic and resistance exercise improved overall MoCA scores as well as in subdomains of attention [ 152 ]. In terms of long-term effect, body-based intervention (Hedges’g = -0.700) is slightly less efficacious in reducing depressive symptoms after the follow-up period than mind-based interventions (Hedges’g = -0.802). Interestingly, both short- and long-term effects of body-based interventions were less than mind-based interventions, and the major reason for such phenomenon might be the nature of the interventions. For instance, previous publications indicated that mind-based interventions involve active control of emotion and contain a procedure that results in a mental state characterized by nonjudgmental awareness of the experience of the present moment [ 155 ]. In other words, mind-based interventions are more direct patterns in altering thoughts and emotional regulation compared with body-based interventions. Despite of less efficacious than mind-based interventions, body-based interventions also achieved approximately large effects in long-term post-stroke depression recovery. Regarding the mechanisms of long-term effects, hormone levels modulated by body-based interventions may contribute to the improvement of depressive symptoms. Cortisol secretion abnormalities can lead to mental health issues and constitute one of the numerous hormonal disorders that accompany these symptoms, such as depression. Also, approximately half of patients with recently diagnosed depression have been shown to secrete abnormal amounts of cortisol [ 156 ]. However, based on a meta-analysis study, body-based intervention, especially physical exercise, can reduce the cortisol level [ 157 ]. In other words, depressive symptoms may be improved by reducing cortisol levels which can be altered by body-based interventions. In addition to cortisol, oxytocin may also be involved in regulating depressive symptoms in the opposite direction. Several animal studies showed that both acute and chronic treatment with oxytocin may decrease the immobility duration in forced swimming test suggesting improvement in depressive symptoms [ 158 ] , [ 159 ]. Also, clinical studies revealed that a decreased level of oxytocin in plasma was observed in patients with MDD compared with control group [ 160 ]. In general, existing evidence may suggest that oxytocin levels might be negatively correlated with depressive severity. However, another animal study conducted a regular aerobic voluntary exercise in female mice for 6 weeks, and the results showed that oxytocin levels increased in brain and serum samples after interventions compared with control group [ 161 ]. Altogether, the above evidence may suggest that regular body-based intervention, especially aerobic exercise, may provide a long-term effect on depression recovery by increasing oxytocin levels. In terms of both short- and long-term effect, combined interventions (Hedges’g = -0.805, -0.994) have shown significant improvements in reducing PSD, with an overall effect size exceeding those of mind-based interventions (Hedges’g = -0.549, -0.802) and body-based interventions (Hedges’g = -0.532, -0.700), suggesting that combined interventions are more effective than individual ones. As discussed earlier, the integration of exercise and mindfulness facilitates bidirectional regulation [ 125 , 127 , 128 ]. In addition to the long-term benefits that mindfulness itself brings to mental health, mindfulness enhances attention and awareness, improving motor control and coordination, and offering positive reinforcement to exercise [ 162 – 164 ]. This contributes to strengthening and consolidating the effects of physical activity. Furthermore, combined intervention such as Tai Chi is considered an acceptable intervention for stroke survivors, with studies demonstrating high adherence rates and positive participant feedback [ 165 , 166 ]. This also lays a solid foundation for long-term effects. The total time of mind- and body-based interventions was found to be a significant predictor for their efficacy on post-stroke depression outcomes. This finding aligns with previous indications that superior efficacy was observed on shorter intervention time [ 167 , 168 ]. Given that both long and short interventions are efficacious, shorter interventions bring a higher rate of positive experiences reported from participants generating superiority, whereas on longer interventions impaired adherence is usually observed in participants [ 167 , 169 , 170 ]. Effect sizes of included studies were not associated with other potential factors including age, sex, severity of depression, total number of sessions, and duration of per session. Possible explanations are that mind-and body-based interventions can overcome the variabilities derived from sex, age, and depression state of patients with poststroke depression and the extent to which the efficacy on poststroke depression may not accumulate over time and the number of training sessions. Further optimization of effects on poststroke depression via a balance between rehabilitation adherence and total duration of interventions is suggested [ 171 , 172 ]. 5. Limitations of the review This review has several limitations. One primary limitation is the exclusion of articles published in languages other than English. This restriction diminishes the breadth and diversity of the available evidence and may introduce language bias, potentially overlooking relevant studies that could offer valuable insights into the topic. Additionally, the heterogeneity among the included studies could limit the generalizability of the findings. Variations in populations, interventions, and outcomes may all impact the conclusions drawn from the meta-analysis. 6. Conclusions The systematic review and meta-analysis found that all mind- and body-based interventions have significant improvement in post-stroke depression, and combined interventions are more effective than mind-based or body-based interventions alone. It’s suggested to integrate additional mindfulness elements into the daily exercises of stroke survivors in clinical practice can further alleviate depressive symptoms. Abbreviations BDI Beck Depression Inventory CES-D Center for Epidemiologic Studies Depression Scale GDS Geriatric Depression Scale HADS Hospital Anxiety and Depression Scale GHQ General Health Questionnaire HAMD Hamilton Depression Rating Scale MDI Major Depression Inventor PHQ Patient Health Questionnaire PMS Depression in Profile of Mood State SDS Self-Rating Depression Scale Declarations Declaration of conflicting interest The authors declare that they have no conflict of interest. Funding statement The authors declare that no funding was received to support the preparation of this systematic review. Author Contribution Conceptualization, and Supervision: FKNK, ZJJ, SVDI; Methodology, Data curation, and Formal analysis: HR, YPB, CJNM, FTKH, ZRR; Writing - original draft: HR, YPB, SVDI; Writing - review & editing: NSPC, LBWM, FKNK. Data Availability All data generated or analyzed during this study are available from the corresponding author on request. References Feigin, V. 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Impact of rehabilitation adherence and depressive symptoms on post-stroke self-care ability and quality of life: a longitudinal study. Top. Stroke Rehabil . 31 , 361–371. https://doi.org/10.1080/10749357.2023.2259652 (2024). Tables Tables 1 to 5 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table110NOV24.docx Table208JAN25.docx Table308JAN25.docx Table408JAN25.docx Table505JAN25.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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K. FONG","email":"","orcid":"","institution":"Department of Rehabilitation Sciences, The Hong Kong Polytechnic University","correspondingAuthor":false,"prefix":"","firstName":"Kenneth","middleName":"N. K.","lastName":"FONG","suffix":""}],"badges":[],"createdAt":"2025-02-04 01:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5954227/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5954227/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":76640588,"identity":"2702b8db-8af1-4742-bc3f-2d89a73a21c8","added_by":"auto","created_at":"2025-02-19 08:10:36","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":314387,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flowchart of study selection\u003c/p\u003e","description":"","filename":"FIgure110NOV24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/620c69319f18168be9b6596f.jpg"},{"id":76641169,"identity":"fbbc4402-a517-402d-ade3-ab31bd33dfd1","added_by":"auto","created_at":"2025-02-19 08:18:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":666614,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of the effect of mind- and body-based interventions on post-stroke depression.\u003c/p\u003e","description":"","filename":"FIgure210NOV24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/bde4981a13c294b5a9a7f16b.jpg"},{"id":76640591,"identity":"8ad3aab4-9843-480a-a929-bcac16cf5ef3","added_by":"auto","created_at":"2025-02-19 08:10:36","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":465692,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of the effect of mind- and body-based interventions on post-stroke depression, including studies with follow-up.\u003c/p\u003e","description":"","filename":"FIgure310NOV24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/a2c770a12e1fd66b7560aadd.jpg"},{"id":76640593,"identity":"c9eec6ac-4ba0-4c3e-8208-3a893c4d22cc","added_by":"auto","created_at":"2025-02-19 08:10:36","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":452945,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of the effect of mind-based interventions on post-stroke depression (A) without follow-up and (B) including studies with follow-up.\u003c/p\u003e","description":"","filename":"FIgure410NOV24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/4cb18251378c8493efad4fa6.jpg"},{"id":76640602,"identity":"fde5365d-2288-40ff-a41a-1d6fe1b80940","added_by":"auto","created_at":"2025-02-19 08:10:37","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2719107,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of the effect of body-based interventions on post-stroke depression (A) without follow-up and (B) including studies with follow-up.\u003c/p\u003e","description":"","filename":"FIgure510NOV24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/6cb976a3bfd1637e46516912.jpg"},{"id":76640616,"identity":"85edff59-2f22-4db5-80ae-ebd936b7c051","added_by":"auto","created_at":"2025-02-19 08:10:38","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":510144,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of the effect of combined mind- and body-based interventions on post-stroke depression (A) without follow-up and (B) including studies with follow-up.\u003c/p\u003e","description":"","filename":"FIgure610NOV24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/210ab5ba5922563aa2a47fcf.jpg"},{"id":76642912,"identity":"a1d4e97a-70d6-4cdf-b81a-5111131d2683","added_by":"auto","created_at":"2025-02-19 08:26:37","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1397679,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-regression of the association between each of the following covariates: (A) mean age, (B) sex, (C) total number of sessions in the intervention, (D) duration per intervention session in minutes, (E) total duration of the intervention in hours, (F) baseline score (depression), and (G) the type of control (1 = exercise or rehabilitation, 2 = psychological-related interventions, 3 = standard/usual care, 4 = No intervention, no treatment, waitlist, or sham intervention, 5 = education), and the effect sizes of mind- and body-based interventions. Each study is represented by a circle proportional to its weight in the analysis.\u003c/p\u003e","description":"","filename":"Figure722OCT24.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/18fe926e049f440e2add399c.jpg"},{"id":99788880,"identity":"be2814c0-5b29-448e-a767-64f24357090b","added_by":"auto","created_at":"2026-01-08 12:48:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7685745,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/13a410ea-3259-4077-9d36-a3653009764c.pdf"},{"id":76642911,"identity":"0e5305d9-01aa-4598-a6bc-b4a7517dc809","added_by":"auto","created_at":"2025-02-19 08:26:36","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14904,"visible":true,"origin":"","legend":"","description":"","filename":"Table110NOV24.docx","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/22d71d93f58fecf5afe57b75.docx"},{"id":76642910,"identity":"2ffbd5c4-6ec4-4d77-af7c-195bfc237f0f","added_by":"auto","created_at":"2025-02-19 08:26:36","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":142640,"visible":true,"origin":"","legend":"","description":"","filename":"Table208JAN25.docx","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/c2e3f2f8482c6faa3c505926.docx"},{"id":76641162,"identity":"0bfc7ce8-d09a-49f8-8580-493ff07f4804","added_by":"auto","created_at":"2025-02-19 08:18:36","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":174947,"visible":true,"origin":"","legend":"","description":"","filename":"Table308JAN25.docx","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/41ad3abf468e34eb68821749.docx"},{"id":76640608,"identity":"294986a2-7c71-4030-8c50-b5c81aa00846","added_by":"auto","created_at":"2025-02-19 08:10:37","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":112888,"visible":true,"origin":"","legend":"","description":"","filename":"Table408JAN25.docx","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/7b37a97db600f3c7de2f489e.docx"},{"id":76640624,"identity":"dc18dfa1-8341-457f-8878-e08934e87887","added_by":"auto","created_at":"2025-02-19 08:10:38","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":16834,"visible":true,"origin":"","legend":"","description":"","filename":"Table505JAN25.docx","url":"https://assets-eu.researchsquare.com/files/rs-5954227/v1/50440c96b25a44f219f751a7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of mind- and body-based interventions on poststroke depression and its neural mechanisms: A systematic review and meta-analysis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eStroke is a leading cause of death and disability worldwide, with over 12\u0026nbsp;million new strokes occurring each year and approximately 101\u0026nbsp;million stroke survivors worldwide. The impact of stroke is profound, resulting in the loss of over 143\u0026nbsp;million years of healthy life annually and a global cost exceeding US\u003cspan\u003e$\u003c/span\u003e721\u0026nbsp;billion, equivalent to approximately 0.66% of the global GDP [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Post-stroke depression (PSD) is one of the common and serious sequelae of stroke. Within two years after a stroke, the incidence of PSD ranges from 11\u0026ndash;41%, affecting approximately one-third of stroke survivors [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It contributes to poor recovery, diminished quality of life, impaired functional abilities, and increased mortality rates [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, the commonly employed approaches for treating PSD involve medication and psychological interventions. However, evidence suggests that the effectiveness of current treatments for PSD only ranges from 30\u0026ndash;40% of all cases [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The exact pathophysiology of PSD remains unclear but is believed to be multifactorial, involving a combination of issues related to ischemic-induced neural damage. Single-drug treatments have yielded inconsistent results, while most proposed composite treatment regimens have failed to deliver desired outcomes, often exposing patients to numerous side effects that further compromise their health and increase the risks of other complications [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Psychological therapies, such as cognitive-behavioral therapy, have shown promising initial findings in improving depressive symptoms associated with PSD. However, the studies in this area have shown high heterogeneity and generally lower quality [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Given the current situation, future directions in PSD treatment call for an integrated approach involving both pharmacological and non-pharmacological strategies. This may include education, mental support, family support, and functional improvement. Exploring additional avenues for positive supplementation is necessary to address the complex nature of PSD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBody-based interventions, as one of the conventional treatment modalities for stroke patients, have ample evidence supporting their ability to enhance motor functions and quality of life. There is increasing evidence suggesting that exercise can also improve depression in the general population [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, research specifically targeting the improvement of PSD through exercise is relatively scarce, with some studies reporting positive impacts but no definitive conclusions.\u003c/p\u003e \u003cp\u003eOn the other hand, mind-based interventions present a potentially valuable alternative approach. They are simple, can be practiced independently anywhere, and are relatively inexpensive with fewer side effects compared to pharmacological treatments. There is evidence suggesting mind-based and mind-body interventions provide potential beneficial effects on depression, as well as the effective alleviation of depressive symptoms in adults with chronic physical conditions through mind-body interventions [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Additionally, research suggests that mind-based interventions can improve cognitive function, which is highly relevant for stroke survivors, as up to 78.7% of them experience some form of cognitive impairment in China [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis systematic review and meta-analysis aims to investigate the effect of mind- and body-based interventions on PSD. It also seeks to explore the neural mechanisms involved and compare the effectiveness of mind- and body-based approaches.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Search strategy\u003c/h2\u003e \u003cp\u003e The systematic review was carried out in accordance with PRISMA guidelines and has been registered on PROSPERO (registration number: CRD42024514565). Two independent reviewers conducted a comprehensive screening of relevant literature from multiple databases, including CINAHL (all fields, Language: English), Cochrane (all fields, Language: English), PsycINFO (no restrictions), PubMed (Randomized Controlled Trial, Clinical Trial, Language: English), and Scopus (article title, abstract, keywords, Language: English, Document type: Article). The search spanned from the inception of the databases to March 11, 2024, and included studies published in English. The search terms are detailed in \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Study selection\u003c/h2\u003e \u003cp\u003eThe inclusion criteria for the studies were as follows: (1) randomized controlled trials (RCTs), (2) inclusion of stroke patients with symptoms of depression evaluated using validated assessment tools, and (3) interventions falling into one of the following categories: body-based interventions, mind-based interventions, or mind-body-based interventions (interventions that belong to both categories). Psychological or counseling interventions were excluded as they were not considered mind-based interventions. Additionally, passive movement interventions, such as passive range of motion exercises and massage were also excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Data extraction\u003c/h2\u003e \u003cp\u003eTwo authors were involved in the data extraction process, conducted in Excel, with one author extracting the data and the other verifying its accuracy. Any disagreement was resolved by a third author. The data extracted from each study included study design, description of the participants, details of the intervention, outcome measures assessed, and reported results of depressive symptoms (Mean and SD). If there was missing or omitted information, data relevant to the review was requested from the authors of the included articles and included in the synthesis, provided a response was received within 14 days.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Risk of bias\u003c/h2\u003e \u003cp\u003eTwo authors independently assessed the quality of reporting and risk of bias for each study using the PEDro scale. Any disagreement was resolved by a third author.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e \u003cp\u003eThe meta-analysis was conducted to compare the effect of mindfulness meditation interventions on depression symptoms with the control group. The Review Manager version 5.4 (Cochrane Collaboration) was used to perform the meta-analysis. To analyze the effect of mindfulness meditation on depression, quantitative data of depressive symptoms measured using validated scales were extracted at baseline, post-test and follow-up. Subgroup analyses were conducted to explore the long-term effects of the mindfulness meditation interventions. Considering the variability of the data, standardized mean differences (SMD) were used to generate effect sizes for the forest plot. A random effect model for meta-analysis was used [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUnivariate meta-regression was conducted with patient demographics, such as age and gender (expressed as the percentage of male patients), clinical information including baseline depression level, and intervention details such as the total duration of the intervention, the total number of sessions, and the type of control setting. Meta-regression was performed to explore potential associations between the aforementioned variables and the weighted Hedge\u0026rsquo;s \u003cem\u003eg\u003c/em\u003e values at the study level. Publication bias was assessed using Egger\u0026rsquo;s test.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003e3.1. Study selection\u003c/h2\u003e\n \u003cp\u003eA total of 1702 records were retrieved from CCTR (n\u0026thinsp;=\u0026thinsp;592), CINAHL (n\u0026thinsp;=\u0026thinsp;123), PsycInfo (n\u0026thinsp;=\u0026thinsp;149), PubMed (n\u0026thinsp;=\u0026thinsp;256) and Scopus (n\u0026thinsp;=\u0026thinsp;582) (Fig.\u0026nbsp;1). 520 duplicate records were excluded and the title and abstract of 1182 were screened. 1013 articles were removed after title and abstract screening. Of the remaining 169 studies, 101 papers were excluded for reasons like not being focused on stroke or depression, lacking mind-body interventions, or not meeting the criteria for RCTs. Finally, out of the 68 studies included in the systematic review, those with missing mean and standard deviation data were excluded from the meta-analysis after attempts to contact the authors for this information proved unsuccessful. As a result, the meta-analysis incorporated data from 54 studies.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003e3.2. Description of the studies included\u003c/h2\u003e\n \u003cp\u003eThe studies included a total of 6825 participants, with males accounting for 70.2% of the total cohort (Table 2). Articles on combined mind and body-based interventions encompassed 893 subjects, while those focusing on mind-based interventions included 207 participants. Studies on body-based interventions comprised 5725 individuals.\u003c/p\u003e\n \u003cp\u003eIn terms of intervention groups, they are divided into three categories. The first category comprises three papers on mind-based interventions involving 73 participants, incorporating relaxation techniques and mindfulness practices without exercise components [17\u0026ndash;19]. The second category, consisting of 65 papers involving 2981 participants, encompasses body-based interventions involving various activities related to the body, such as physical therapy, physical exercise, occupational therapy, and upper and lower limb activities [20\u0026ndash;84]. The third category, comprising 11 papers with 470 participants, focuses on combined mind and body-based interventions that integrate physical activities linked to mindfulness, such as yoga and tai chi,, as well as interventions involving exercises and mindfulness practices [30, 42\u0026ndash;44, 46, 58, 68, 70, 76, 79, 82]. Therefore, all interventions under the combined mind and body-based category also fall within the scope of body-based interventions.\u003c/p\u003e\n \u003cp\u003eThe comparison groups are varied and were classified as follows: 1350 participants were allocated to the exercise or rehabilitation group, 310 individuals were part of control groups involving psychological interventions, 1043 subjects received standard or usual care, 486 participants belonged to the no intervention, no treatment, waitlist, or sham intervention group, and 35 subjects were assigned to educational control groups (Table\u0026nbsp;2).\u003c/p\u003e\n \u003cp\u003eRegarding the intervention sessions and their durations per session, mind-based interventions typically consisted of 8 to 20 sessions, lasting between 80 to 150 minutes per session. Body-based interventions showed a wider range, ranging from 3 to 312 sessions, with session durations varying from 10 to 210 minutes. Combined interventions spanned from 6 to 60 sessions, lasting between 40 to 210 minutes per session. Table 3 shows the depression scores at baseline, post-test, and follow up.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003e3.3. Risk of bias\u003c/h2\u003e\n \u003cdiv\u003e\n \u003cp\u003eThe methodological quality of the included studies was assessed using the PEDro scale. The PEDro scale consists of 11 items that evaluate aspects of study design, methodology, and statistical reporting. Each item is scored as either present (1 point) or absent (0 points), with a maximum possible score of 10 points (the first item is not included in the total score) [85].\u003c/p\u003e\n \u003cp\u003eThe average PEDro score across all included studies was 6.51. Studies on mind-based interventions had an average PEDro score of 6, ranging from 4 to 7. Body-based interventions had an average PEDro score of 6.57, ranging from 4 to 8. Combined interventions had an average PEDro score of 7.44, ranging from 6 to 8 (\u003cstrong\u003eTable\u0026nbsp;4\u003c/strong\u003e). This indicates a good overall methodological quality in the included studies and underscores the variability in methodological quality among them [85].\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003e3.4. Effect size\u003c/h2\u003e\n \u003cp\u003eAccording to Hedges\u0026apos; g values, which categorize effect sizes as small (0.15), medium (0.40), and large (0.75) [86], the meta-analysis results (\u003cstrong\u003eTable\u0026nbsp;5\u003c/strong\u003e) indicate that mind- and body-based interventions, whether used alone or in combination, significantly reduced depressive symptoms compared to the control group (Hedges\u0026rsquo; g = -0.572, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u0026sup2; = 82.51%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cstrong\u003eFig.\u0026nbsp;2\u003c/strong\u003e). The overall significance remained robust during the leave-one-out sensitivity analysis, showing Hedges\u0026rsquo; g values ranging from \u0026minus;\u0026thinsp;0.485 to -0.584, which consistently demonstrate medium effect sizes.\u003c/p\u003e\n \u003cp\u003eThe meta-analysis of 30 studies that included follow-up (n\u0026thinsp;=\u0026thinsp;30, \u003cstrong\u003eTable\u0026nbsp;5\u003c/strong\u003e) showed that mind- and body-based interventions, whether used alone or combined, reduced depressive symptoms from pre-test to follow-up compared to the control (Hedges\u0026rsquo; g = -0.739, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u0026sup2; = 89.77%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cstrong\u003eFig.\u0026nbsp;3\u003c/strong\u003e). The follow-up period ranges from 3 weeks to 12 months suggesting a long-term effect of the interventions.\u003c/p\u003e\n \u003cp\u003eThe subgroup analysis of mind-based interventions (n\u0026thinsp;=\u0026thinsp;4 \u003cstrong\u003eTable\u0026nbsp;5\u003c/strong\u003e) showed a significant reduction of depressive symptoms (Hedges\u0026rsquo; g = -0.549, p\u0026thinsp;=\u0026thinsp;0.001, I\u0026sup2; = 0.000, p\u0026thinsp;=\u0026thinsp;0.497, \u003cstrong\u003eFig.\u0026nbsp;4A\u003c/strong\u003e) compared to the control. Similarly, mind-based interventions significantly reduced depressive symptoms after the follow-up period (n\u0026thinsp;=\u0026thinsp;4, Hedges\u0026rsquo; g = -0.802, p\u0026thinsp;=\u0026thinsp;0.017, I\u0026sup2; = 71.66%, p\u0026thinsp;=\u0026thinsp;0.014, \u003cstrong\u003eFig.\u0026nbsp;4B\u003c/strong\u003e) which ranged from 3 weeks to 12 months.\u003c/p\u003e\n \u003cp\u003eThe subgroup analysis of body-based interventions (n\u0026thinsp;=\u0026thinsp;52, \u003cstrong\u003eTable\u0026nbsp;5\u003c/strong\u003e) showed a significant reduction of depressive symptoms (Hedges\u0026rsquo; g = -0.532, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u0026sup2; = 83.34%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cstrong\u003eFig.\u0026nbsp;5A\u003c/strong\u003e) compared to the control. Similarly, body-based interventions significantly reduced depressive symptoms after the follow-up period (n\u0026thinsp;=\u0026thinsp;22, Hedges\u0026rsquo; g = -0.700, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u0026sup2; = 91.33%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cstrong\u003eFig.\u0026nbsp;5B\u003c/strong\u003e) which ranged from 3 weeks to 12 months.\u003c/p\u003e\n \u003cp\u003eCombined mind- and body-based interventions (n\u0026thinsp;=\u0026thinsp;10) significantly reduced depressive symptoms compared to the control (Hedges\u0026rsquo; g = -0.805, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u0026sup2; = 80.99%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cstrong\u003eFig.\u0026nbsp;6A\u003c/strong\u003e). Similarly, combined mind- and body-based interventions significantly reduced depressive symptoms after the follow-up period (n\u0026thinsp;=\u0026thinsp;4, Hedges\u0026rsquo; g = -0.994, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u0026sup2; = 77.14%, p\u0026thinsp;=\u0026thinsp;0.004, \u003cstrong\u003eFig.\u0026nbsp;6B\u003c/strong\u003e) which ranged from 3 weeks to 12 months. The univariate meta-regression analysis showed a negative relationship between the total duration of the intervention in hours and the effect size (p\u0026thinsp;=\u0026thinsp;0.045, \u003cstrong\u003eFig.\u0026nbsp;7\u003c/strong\u003e).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe study aimed to investigate and compare the effects of mind- and body-based interventions on PSD. At post-intervention and follow-up, all interventions involving mind-based, body-based, and combined approaches showed significant improvements in PSD. A negative and significant relationship was observed between the overall duration of interventions and the degree of PSD improvement.\u003c/p\u003e \u003cp\u003eAll four categories show studies with good quality (average PEDro score\u0026thinsp;\u0026ge;\u0026thinsp;6) though wherein 40% studies (2/5) with fair quality in the category of mind-based intervention and 13.85% studies (9/65) with fair quality in the category of body-based intervention [\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e]. Reduced methodological quality mainly results from the limitation of mind- and body-based interventions per se that are difficult for subjects and therapists blinding [\u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e88\u003c/span\u003e]. The result of the risk of bias assessments presents that included studies can offer reliable and valid results while being clustered into the current categories. Nevertheless, the interpretation of current results that included mind-based interventions require more caution, contrasted to results solely from the category of body-based interventions, as PEDro (designed for physiotherapy practice) may not satisfy inherent components of mindfulness like cultural context resulting in inaccurate appraisal, probably underestimated quality of study in the current review [\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e89\u003c/span\u003e]. Future studies may choose an ideal assessment tool and/or set suitable thresholds for assessment results, based on included study designs, to measure the studies\u0026rsquo; \u0026lsquo;real\u0026rsquo; quality for critical appraisal and more robust interpretation of results.\u003c/p\u003e \u003cp\u003eStudies show that engaging in physical activities can significantly improve depression, a fact well-established in both the general population and patients with depression [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e, \u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e]. Research reveals that depressive symptoms in stroke patients decrease right after exercise [\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e92\u003c/span\u003e]. For stroke survivors, engaging in physical activities not only improves motor functions like muscle strength, range of motion, balance, and walking but also enhances cognitive abilities and levels of independence in daily activities [\u003cspan additionalcitationids=\"CR94\" citationid=\"CR93\" class=\"CitationRef\"\u003e93\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e]. These improvements are inversely associated with the depressive symptoms experienced by stroke [\u003cspan additionalcitationids=\"CR97 CR98\" citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR99\" class=\"CitationRef\"\u003e99\u003c/span\u003e]. Mindfulness cultivates awareness of present experiences and an attitude of non-judgmental acceptance of current experiences [\u003cspan citationid=\"CR100\" class=\"CitationRef\"\u003e100\u003c/span\u003e]. Mindfulness can help individuals better cope with adversity [\u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e]. In stroke patients, mindfulness has been associated with a reduction in depressive symptoms [\u003cspan citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e, \u003cspan citationid=\"CR103\" class=\"CitationRef\"\u003e103\u003c/span\u003e]. Mindfulness interventions can adjust depression-related mediators, such as breaking patterns of rumination, and boosting resilience that acts as a protective factor against PSD [\u003cspan additionalcitationids=\"CR105\" citationid=\"CR104\" class=\"CitationRef\"\u003e104\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR106\" class=\"CitationRef\"\u003e106\u003c/span\u003e]. Additionally, mindfulness has been found to alleviate fatigue related to neurological conditions, improve motor imagery post-stroke, and enhance cognitive performance in the general population [\u003cspan additionalcitationids=\"CR108 CR109 CR110\" citationid=\"CR107\" class=\"CitationRef\"\u003e107\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR111\" class=\"CitationRef\"\u003e111\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePSD is closely linked to the brain changes that occur following a stroke, leading to the disruption of key pathways responsible for emotion regulation [\u003cspan citationid=\"CR112\" class=\"CitationRef\"\u003e112\u003c/span\u003e]. This disruption involves the monoamine systems, glutamatergic systems, excitotoxicity, the gut-brain axis, neuroinflammation, and abnormal neutrophil responses [\u003cspan citationid=\"CR112\" class=\"CitationRef\"\u003e112\u003c/span\u003e, \u003cspan citationid=\"CR113\" class=\"CitationRef\"\u003e113\u003c/span\u003e]. From a neuromechanistic perspective, both body and mind interventions can induce significant neuroplasticity [\u003cspan additionalcitationids=\"CR115 CR116 CR117 CR118\" citationid=\"CR114\" class=\"CitationRef\"\u003e114\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR119\" class=\"CitationRef\"\u003e119\u003c/span\u003e]. In individuals with cerebral ischemia, exercise improves dendritic and axonal plasticity, promoting neural pathway reconstruction [\u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e]. Mindfulness can have an impact on specific brain regions; practicing meditation is associated with increased neural activation in regions like the insula, frontal lobe, prefrontal cortex, and hippocampus, potentially leading to improvements in cortical thickness and brain functional connectivity [\u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e, \u003cspan citationid=\"CR117\" class=\"CitationRef\"\u003e117\u003c/span\u003e]. Both exercise and mindfulness can regulate inflammation factors and induce the increase of neurotrophic factors like BDNF [\u003cspan additionalcitationids=\"CR122\" citationid=\"CR121\" class=\"CitationRef\"\u003e121\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR123\" class=\"CitationRef\"\u003e123\u003c/span\u003e]. Low levels of BDNF are strongly associated with the risk of post-stroke depression [\u003cspan citationid=\"CR124\" class=\"CitationRef\"\u003e124\u003c/span\u003e]. Exercise also inhibits glutamate expression, and reduces brain damage. Furthermore, it is believed that meditation reduces cortisol levels top-down by altering brain regions, while the body adapts bottom-up to exercise [\u003cspan citationid=\"CR125\" class=\"CitationRef\"\u003e125\u003c/span\u003e, \u003cspan citationid=\"CR126\" class=\"CitationRef\"\u003e126\u003c/span\u003e]. These changes and adaptations ultimately contribute to regulating the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the gut-brain axis [\u003cspan citationid=\"CR125\" class=\"CitationRef\"\u003e125\u003c/span\u003e, \u003cspan citationid=\"CR127\" class=\"CitationRef\"\u003e127\u003c/span\u003e, \u003cspan citationid=\"CR128\" class=\"CitationRef\"\u003e128\u003c/span\u003e]. Together, these neurobiological mechanisms associated with exercise and mindfulness work to alleviate post-stroke neuroinflammation, aid in the reconstruction of neural pathways, and regulate emotions. The combination of interventions focusing on physical rehabilitation and mental health forms a connection between the body and mind which holds the potential to generate benefits that go beyond the mere sum of the individual interventions [\u003cspan citationid=\"CR126\" class=\"CitationRef\"\u003e126\u003c/span\u003e]. Those effective interventions for PSD can lead to improved mental well-being, better functions and social interactions, and enhanced overall quality of life for stroke survivors.\u003c/p\u003e \u003cp\u003eThe meta-analysis results indicate that the effectiveness of mind and body-based interventions during the follow-up period remained significant, with each intervention type showing a higher effect size at the end of follow-up compared to post-intervention. This suggests the presence of long-term effects of interventions (ranging from 3 weeks to 12 months). Animal studies indicate that animals engaging in exercise within 24 hours after a stroke exhibit improved behavioral outcomes and reduced ischemic volume [\u003cspan citationid=\"CR129\" class=\"CitationRef\"\u003e129\u003c/span\u003e]. It is believed by researchers that early neuroplasticity post-stroke is more robust, and early physical interventions can prevent learned overuse of the unaffected side, thereby beneficially impacting cortical reorganization, which may continue to have a positive effect on PSD [\u003cspan citationid=\"CR129\" class=\"CitationRef\"\u003e129\u003c/span\u003e, \u003cspan citationid=\"CR130\" class=\"CitationRef\"\u003e130\u003c/span\u003e]. Additionally, both physical and mindfulness interventions contribute to reducing the risk of post-stroke complications. Exercise can reduce the risk of muscle atrophy, pressure ulcers, and cardiovascular diseases, while interventions based on mindfulness may assist in alleviating chronic pain [\u003cspan additionalcitationids=\"CR132 CR133 CR134\" citationid=\"CR131\" class=\"CitationRef\"\u003e131\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR135\" class=\"CitationRef\"\u003e135\u003c/span\u003e]. Both exercise and mindfulness provide patients with valuable coping mechanisms and strategies, finally improving their quality of life and alleviating PSD [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e, \u003cspan citationid=\"CR136\" class=\"CitationRef\"\u003e136\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMind-based interventions alone significantly reduced depressive symptoms after the intervention (Hedges\u0026rsquo;g = -0.549, Fig.\u0026nbsp;4), and this effect was sustained during the follow-up period (Hedges\u0026rsquo;g = -0.802, Fig.\u0026nbsp;4), which lasted from 3 to 12 weeks post-intervention. Mindfulness-based recovery programs for stroke survivors may not only help lower stress levels and enhance recovery behaviors but also significantly reduce post-stroke depression by fostering deeper insights and creating a supportive community throughout the recovery journey [\u003cspan citationid=\"CR137\" class=\"CitationRef\"\u003e137\u003c/span\u003e]. Mindfulness alleviates depression partially through emotional regulation mechanisms, particularly by enhancing cognitive reappraisal and reducing expressive suppression [\u003cspan citationid=\"CR138\" class=\"CitationRef\"\u003e138\u003c/span\u003e]. Emotional regulation strategies, such as reappraisal, which involve reframing the meaning of a situation, are negatively associated with depression, while expressive suppression correlates positively with depressive symptoms [\u003cspan citationid=\"CR139\" class=\"CitationRef\"\u003e139\u003c/span\u003e, \u003cspan citationid=\"CR140\" class=\"CitationRef\"\u003e140\u003c/span\u003e]. Mindfulness interventions promote reappraisal as a key component, leading to improved emotional outcomes [\u003cspan citationid=\"CR141\" class=\"CitationRef\"\u003e141\u003c/span\u003e]. Additionally, mindfulness has been linked to reduced rumination, a maladaptive thought pattern that perpetuates depression, suggesting that it may mediate the relationship between mindfulness and depressive symptoms [\u003cspan citationid=\"CR142\" class=\"CitationRef\"\u003e142\u003c/span\u003e, \u003cspan citationid=\"CR143\" class=\"CitationRef\"\u003e143\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStructural changes in brain regions have been associated with improvements in depressive symptoms through mind-based interventions [\u003cspan citationid=\"CR144\" class=\"CitationRef\"\u003e144\u003c/span\u003e]. Meditation practice can influence self-referential processing and enhance present-moment awareness, leading to alterations in the default mode networks, particularly the midline prefrontal cortex and posterior cingulate cortex, which are associated with self-awareness [\u003cspan citationid=\"CR145\" class=\"CitationRef\"\u003e145\u003c/span\u003e]. Changes in fronto-limbic networks have also been linked to attention and self-awareness, suggesting that these alterations following mindfulness practice may facilitate the treatment of depression [\u003cspan citationid=\"CR144\" class=\"CitationRef\"\u003e144\u003c/span\u003e]. Also, mindfulness-based interventions have been associated with increased cortical thickness in the insula and somatosensory cortex, correlating with reductions in worry, state anxiety, and depression [\u003cspan citationid=\"CR145\" class=\"CitationRef\"\u003e145\u003c/span\u003e]. When comparing the effect size of mind- and body-based interventions alone, the magnitude of the effect is similar (n\u0026thinsp;=\u0026thinsp;4, Hedges\u0026rsquo; g = -0.549; n\u0026thinsp;=\u0026thinsp;52, Hedges\u0026rsquo; g = -0.532, respectively) suggesting that either intervention alone may be beneficial. Interestingly, an intervention combining both mind- and body-based approaches results in an even larger effect on post-stroke depression (n\u0026thinsp;=\u0026thinsp;10, Hedges\u0026rsquo; g = -0.805). The compelling evidence of structural brain changes and enhanced self-awareness resulting from mindfulness practices underscores the transformative potential of integrating both mind- and body-based interventions to significantly alleviate post-stroke depression and improve overall well-being.\u003c/p\u003e \u003cp\u003eBased on results from the meta-analysis, body-based interventions significantly reduce depressive symptoms compared to the control group (Fig.\u0026nbsp;5). In terms of short-term effect size (Table\u0026nbsp;5), the effect of body-based interventions (Hedges\u0026rsquo;g = -0.532) is lower than combined mind- and body-based interventions (Hedges\u0026rsquo;g = -0.805). Body-based interventions (Hedges\u0026rsquo;g = -0.532) may result in slightly less pronounced recovery from depression compared to mind-based interventions (Hedges\u0026rsquo;g = -0.549). Although the effect was smaller than mind-based and combined interventions, the effect size of body-based interventions was generated by a larger amount of studies than mind-based and combined interventions, which may indicate the results of body-based interventions may have higher reliability.\u003c/p\u003e \u003cp\u003eRegarding the underlying mechanism of body-based intervention in reducing depression, brain plasticity may be a significant factor. Brain plasticity was deemed as changes in multiple domains, like structure rebuilding and function activating, which are abnormal in key brain regions of depression patients [\u003cspan citationid=\"CR146\" class=\"CitationRef\"\u003e146\u003c/span\u003e]. Evidence from an animal study showed that four weeks of treadmill aerobic exercise resulted in a significant increase in the total volume of dentate gyrus (DG) and CA1 of rats treated by chronic unpredictable stress model [\u003cspan citationid=\"CR147\" class=\"CitationRef\"\u003e147\u003c/span\u003e]. In addition, another review article also indicated that major depressive disorder (MDD) patients have been found to have a decreased hippocampus volume, specifically DG atrophy, whereas individuals with MDD who are on medication show normal, even greater, DG volumes when compared to those who are not currently receiving treatment for MDD [\u003cspan citationid=\"CR148\" class=\"CitationRef\"\u003e148\u003c/span\u003e]. Overall, the above evidence suggests that body-based interventions may reduce depressive symptoms by modulating and rebuilding brain structures, especially DG. Function activating is also involved in brain plasticity, and many studies that focused on event-related potential (ERP) showed exercise can activate brain function in depressive patients. For instance, a randomized control trial demonstrated that moderate-intensity exercise increases N2 amplitude and decreases BDI-II scores, indicating improved cognitive control and reduced depression symptoms brought by exercise [\u003cspan citationid=\"CR149\" class=\"CitationRef\"\u003e149\u003c/span\u003e]. Furthermore, another study also showed mediative aerobic exercise significantly increased N2 and P3 amplitudes and reduced BDI-II scores, suggesting aerobic exercise can activate cerebral cortical neuronal excitability and therefore decrease depressive symptoms [\u003cspan citationid=\"CR150\" class=\"CitationRef\"\u003e150\u003c/span\u003e]. In summary, body-based intervention, especially aerobic exercise, can activate brain functions to achieve favorable changes in EPR in depressed patients.\u003c/p\u003e \u003cp\u003eExcepting the clinical implication in improving depressive symptoms, body-based interventions can also provide multidimensional benefits including motor function recovery and cognitive improvement to post-stroke depression patients [\u003cspan citationid=\"CR151\" class=\"CitationRef\"\u003e151\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e [\u003cspan citationid=\"CR152\" class=\"CitationRef\"\u003e152\u003c/span\u003e]. According to previous evidence, a community-based study in Auckland, New Zealand that lasted one year showed that 88% of the 680 stroke patients had hemiparesis, which suggested a large proportion of stroke survivors suffered from motor function deficits [\u003cspan citationid=\"CR153\" class=\"CitationRef\"\u003e153\u003c/span\u003e]. In this way, in addition to improving depressive symptoms, body-based interventions, like aerobic and resistance exercise programs were also effective ways to improve motor functions [\u003cspan citationid=\"CR154\" class=\"CitationRef\"\u003e154\u003c/span\u003e]. Regarding cognitive functions, similarly, a clinical trial showed that the combination of aerobic and resistance exercise improved overall MoCA scores as well as in subdomains of attention [\u003cspan citationid=\"CR152\" class=\"CitationRef\"\u003e152\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn terms of long-term effect, body-based intervention (Hedges\u0026rsquo;g = -0.700) is slightly less efficacious in reducing depressive symptoms after the follow-up period than mind-based interventions (Hedges\u0026rsquo;g = -0.802). Interestingly, both short- and long-term effects of body-based interventions were less than mind-based interventions, and the major reason for such phenomenon might be the nature of the interventions. For instance, previous publications indicated that mind-based interventions involve active control of emotion and contain a procedure that results in a mental state characterized by nonjudgmental awareness of the experience of the present moment [\u003cspan citationid=\"CR155\" class=\"CitationRef\"\u003e155\u003c/span\u003e]. In other words, mind-based interventions are more direct patterns in altering thoughts and emotional regulation compared with body-based interventions.\u003c/p\u003e \u003cp\u003eDespite of less efficacious than mind-based interventions, body-based interventions also achieved approximately large effects in long-term post-stroke depression recovery. Regarding the mechanisms of long-term effects, hormone levels modulated by body-based interventions may contribute to the improvement of depressive symptoms. Cortisol secretion abnormalities can lead to mental health issues and constitute one of the numerous hormonal disorders that accompany these symptoms, such as depression. Also, approximately half of patients with recently diagnosed depression have been shown to secrete abnormal amounts of cortisol [\u003cspan citationid=\"CR156\" class=\"CitationRef\"\u003e156\u003c/span\u003e]. However, based on a meta-analysis study, body-based intervention, especially physical exercise, can reduce the cortisol level [\u003cspan citationid=\"CR157\" class=\"CitationRef\"\u003e157\u003c/span\u003e]. In other words, depressive symptoms may be improved by reducing cortisol levels which can be altered by body-based interventions. In addition to cortisol, oxytocin may also be involved in regulating depressive symptoms in the opposite direction. Several animal studies showed that both acute and chronic treatment with oxytocin may decrease the immobility duration in forced swimming test suggesting improvement in depressive symptoms [\u003cspan citationid=\"CR158\" class=\"CitationRef\"\u003e158\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e [\u003cspan citationid=\"CR159\" class=\"CitationRef\"\u003e159\u003c/span\u003e]. Also, clinical studies revealed that a decreased level of oxytocin in plasma was observed in patients with MDD compared with control group [\u003cspan citationid=\"CR160\" class=\"CitationRef\"\u003e160\u003c/span\u003e]. In general, existing evidence may suggest that oxytocin levels might be negatively correlated with depressive severity. However, another animal study conducted a regular aerobic voluntary exercise in female mice for 6 weeks, and the results showed that oxytocin levels increased in brain and serum samples after interventions compared with control group [\u003cspan citationid=\"CR161\" class=\"CitationRef\"\u003e161\u003c/span\u003e]. Altogether, the above evidence may suggest that regular body-based intervention, especially aerobic exercise, may provide a long-term effect on depression recovery by increasing oxytocin levels.\u003c/p\u003e \u003cp\u003eIn terms of both short- and long-term effect, combined interventions (Hedges\u0026rsquo;g = -0.805, -0.994) have shown significant improvements in reducing PSD, with an overall effect size exceeding those of mind-based interventions (Hedges\u0026rsquo;g = -0.549, -0.802) and body-based interventions (Hedges\u0026rsquo;g = -0.532, -0.700), suggesting that combined interventions are more effective than individual ones. As discussed earlier, the integration of exercise and mindfulness facilitates bidirectional regulation [\u003cspan citationid=\"CR125\" class=\"CitationRef\"\u003e125\u003c/span\u003e, \u003cspan citationid=\"CR127\" class=\"CitationRef\"\u003e127\u003c/span\u003e, \u003cspan citationid=\"CR128\" class=\"CitationRef\"\u003e128\u003c/span\u003e]. In addition to the long-term benefits that mindfulness itself brings to mental health, mindfulness enhances attention and awareness, improving motor control and coordination, and offering positive reinforcement to exercise [\u003cspan additionalcitationids=\"CR163\" citationid=\"CR162\" class=\"CitationRef\"\u003e162\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR164\" class=\"CitationRef\"\u003e164\u003c/span\u003e]. This contributes to strengthening and consolidating the effects of physical activity. Furthermore, combined intervention such as Tai Chi is considered an acceptable intervention for stroke survivors, with studies demonstrating high adherence rates and positive participant feedback [\u003cspan citationid=\"CR165\" class=\"CitationRef\"\u003e165\u003c/span\u003e, \u003cspan citationid=\"CR166\" class=\"CitationRef\"\u003e166\u003c/span\u003e]. This also lays a solid foundation for long-term effects.\u003c/p\u003e \u003cp\u003eThe total time of mind- and body-based interventions was found to be a significant predictor for their efficacy on post-stroke depression outcomes. This finding aligns with previous indications that superior efficacy was observed on shorter intervention time [\u003cspan citationid=\"CR167\" class=\"CitationRef\"\u003e167\u003c/span\u003e, \u003cspan citationid=\"CR168\" class=\"CitationRef\"\u003e168\u003c/span\u003e]. Given that both long and short interventions are efficacious, shorter interventions bring a higher rate of positive experiences reported from participants generating superiority, whereas on longer interventions impaired adherence is usually observed in participants [\u003cspan citationid=\"CR167\" class=\"CitationRef\"\u003e167\u003c/span\u003e, \u003cspan citationid=\"CR169\" class=\"CitationRef\"\u003e169\u003c/span\u003e, \u003cspan citationid=\"CR170\" class=\"CitationRef\"\u003e170\u003c/span\u003e]. Effect sizes of included studies were not associated with other potential factors including age, sex, severity of depression, total number of sessions, and duration of per session. Possible explanations are that mind-and body-based interventions can overcome the variabilities derived from sex, age, and depression state of patients with poststroke depression and the extent to which the efficacy on poststroke depression may not accumulate over time and the number of training sessions. Further optimization of effects on poststroke depression via a balance between rehabilitation adherence and total duration of interventions is suggested [\u003cspan citationid=\"CR171\" class=\"CitationRef\"\u003e171\u003c/span\u003e, \u003cspan citationid=\"CR172\" class=\"CitationRef\"\u003e172\u003c/span\u003e].\u003c/p\u003e"},{"header":"5. Limitations of the review","content":"\u003cp\u003eThis review has several limitations. One primary limitation is the exclusion of articles published in languages other than English. This restriction diminishes the breadth and diversity of the available evidence and may introduce language bias, potentially overlooking relevant studies that could offer valuable insights into the topic. Additionally, the heterogeneity among the included studies could limit the generalizability of the findings. Variations in populations, interventions, and outcomes may all impact the conclusions drawn from the meta-analysis.\u003c/p\u003e"},{"header":"6. Conclusions","content":"\u003cp\u003eThe systematic review and meta-analysis found that all mind- and body-based interventions have significant improvement in post-stroke depression, and combined interventions are more effective than mind-based or body-based interventions alone. It\u0026rsquo;s suggested to integrate additional mindfulness elements into the daily exercises of stroke survivors in clinical practice can further alleviate depressive symptoms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBDI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBeck Depression Inventory\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCES-D\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCenter for Epidemiologic Studies Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGeriatric Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHADS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHospital Anxiety and Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGHQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGeneral Health Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHAMD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHamilton Depression Rating Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMDI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMajor Depression Inventor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePHQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatient Health Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDepression in Profile of Mood State\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSelf-Rating Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclaration of conflicting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\u003ch2\u003eFunding statement\u003c/h2\u003e \u003cp\u003eThe authors declare that no funding was received to support the preparation of this systematic review.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization, and Supervision: FKNK, ZJJ, SVDI; Methodology, Data curation, and Formal analysis: HR, YPB, CJNM, FTKH, ZRR; Writing - original draft: HR, YPB, SVDI; Writing - review \u0026amp; editing: NSPC, LBWM, FKNK.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are available from the corresponding author on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFeigin, V. 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Stroke Rehabil\u003c/em\u003e. \u003cb\u003e31\u003c/b\u003e, 361\u0026ndash;371. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/10749357.2023.2259652\u003c/span\u003e\u003cspan address=\"10.1080/10749357.2023.2259652\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"body-based interventions, exercise, mind-based interventions, mindfulness, post-stroke depression, stroke","lastPublishedDoi":"10.21203/rs.3.rs-5954227/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5954227/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePost-stroke depression (PSD) is recognized as the most common psychiatric disorder following a stroke, impacting the subsequent recovery and quality of life of stroke survivors. In recent years, physical activities and mindfulness have been proven to improve depression, however, it remained unknown whether those interventions were also effective in the treatment of PSD. This systematic review aims to assess the effects of mind- and body-based interventions on PSD and their underlying neural mechanisms. The systematic review (PROSPERO registration number: CRD42024514565) searched CINAHL, Cochrane, PsycINFO, PubMed, and Scopus up to March 11, 2024, focusing on English-language studies. Inclusion criteria encompassed randomized controlled trials of stroke patients with depression using validated assessment tools, targeting body-based, mind-based, or mind-body interventions, while excluding psychological or counseling interventions and passive movements. Two authors conducted data extraction with checks for accuracy, and risk of bias was assessed using the PEDro scale, which evaluates study design and methodology, yielding a maximum score of 10 points. Data extraction and risk of bias assessment were conducted by independent reviewers. A total of 68 studies were included, involving 6,825 participants, and 54 of these studies were included in the meta-analysis. The average PEDro score of 6.51 indicates good methodological quality, with combined interventions scoring highest at 7.44, highlighting variability among the studies. Meta-analysis results demonstrate that all mind- and body-based interventions have a significant impact on PSD (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with effect sizes as follows: all mind- and body-based interventions (n\u0026thinsp;=\u0026thinsp;66, Hedges\u0026rsquo; g = -0.572), mind-based interventions (n\u0026thinsp;=\u0026thinsp;4, Hedges\u0026rsquo; g = -0.549), body-based interventions (n\u0026thinsp;=\u0026thinsp;52, Hedges\u0026rsquo; g = -0.532), and combined interventions (n\u0026thinsp;=\u0026thinsp;10, Hedges\u0026rsquo; g = -0.805). The systematic review and meta-analysis revealed that all mind- and body-based interventions significantly improved post-stroke depression, and combined interventions are more effective than mind-based or body-based interventions alone. It is suggested to integrate additional mindfulness elements into the daily exercises of stroke survivors in clinical practice can further alleviate depressive symptoms.\u003c/p\u003e","manuscriptTitle":"The effect of mind- and body-based interventions on poststroke depression and its neural mechanisms: A systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-19 08:10:31","doi":"10.21203/rs.3.rs-5954227/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a79545ea-7bfe-458f-957d-c3cca12acf38","owner":[],"postedDate":"February 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":44216471,"name":"Health sciences/Neurology"},{"id":44216472,"name":"Health sciences/Neurology/Neurological disorders"}],"tags":[],"updatedAt":"2026-01-01T08:23:50+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-19 08:10:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5954227","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5954227","identity":"rs-5954227","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}