A Study on Mahjong Intervention to improve Cognitive Impairment in Patients with Schizophrenia: a pilot, single-blind, randomized, controlled trial

doi:10.21203/rs.3.rs-4665271/v1

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A Study on Mahjong Intervention to improve Cognitive Impairment in Patients with Schizophrenia: a pilot, single-blind, randomized, controlled trial

https://doi.org/10.21203/rs.3.rs-4665271/v1

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Objective

Mahjong, a traditional Chinese tile-based game, has been widely reported to be closely associated with better cognitive function. However, its effects on the cognitive function of patients with schizophrenia have not yet been studied.

Method

In a pilot study, 49 patients diagnosed with schizophrenia were randomly assigned to the intervention group (Mahjong combined with standard treatment) and the control group (standard treatment). The intervention group engaged in cognitive training through Mahjong for 2 hours per day, 4 days per week for 12 weeks. Primary cognitive outcomes were assessed using Cambridge Neuropsychological Test Automated Battery (CANTAB), while secondary outcomes were evaluated with the Positive and Negative Syndrome Scale (PANSS), and the Self-report Quality of Life Measure for People with Schizophrenia (SQLS). Assessments were conducted at baseline (T0), the 4th week (T1), the 8th week (T2), and the 12th week (T3).

Results

There is a significant group-by-time interaction effect in RTI and time effect in PAL. The intervention group showed significant improvements in reaction time and movement time of response to a visual target, visual memory and new learning at T3 compared to baseline. Additionally, the intervention group exhibited significant improvements in SQLS over time.

Conclusion

While this pilot study suggests that prolonged Mahjong intervention may benefit certain cognitive functions and quality of life in patients with schizophrenia, these findings should be interpreted with caution. Further research with larger, more diverse samples and longer follow-up periods is necessary to confirm and extend these findings.

Trial registration:

The trial is registered with https://www.chictr.org.cn/ under registration number ChiCTR2400083439 (date of registration: 2024-01-25).

Schizophrenia

Mahjong

Cognitive Function

Quality of life

Mental disorders remain one of the top ten global burdens, and schizophrenia has one of the highest measured Years Lived with Disability among all diseases, injuries, and risk factors [1]. Cognitive deficits have long been considered a core symptom of schizophrenia and are significant factors leading to disability and treatment refractoriness in schizophrenia patients [2, 3]. These deficits are pervasive, affecting processing speed, verbal memory, working memory, attention, and executive functions [2, 4, 5]. Various cognitive deficits in schizophrenia are closely related to functional outcomes and quality of life [6], posing major obstacles to maintaining work and social life [5, 7]. Therefore, improving cognitive deficits in schizophrenia has garnered increasing attention [8].

Despite significant achievements in treating acute and maintenance phases of schizophrenia [9–11], cognitive deficits have not been adequately addressed [12], with only a few antipsychotic drugs showing potential cognitive benefits [13]. Moreover, the molecular targets for treating cognitive deficits mentioned in the MATRICS have not been sufficiently proven to have cognitive benefits [14–17]. The adjunctive use of cognitive enhancers for schizophrenia patients has shown limited positive effects and lacks evidence to support long-term use [18, 19]. Even promising treatments like transcranial direct current stimulation still require more refinement in therapeutic parameters for restoring cognitive function in schizophrenia patients [20–22].

Cognitive remediation (CR), a widely proven treatment to improve cognitive function [23, 24], but efforts continue to promote CR as a routine treatment for schizophrenia patients [25]. Trained therapists, cognitive exercises, development of cognitive strategies, and facilitating the transfer of cognitive gains to daily functioning are vital factor in the success of CR in producing a cognitive effect [23, 26]. Even relatively more convenient computerized CR still requires supplementary human guidance to achieve greater cognitive benefits [27]. However, not all regions have enough trained psychiatrists [28]. This issue is more pronounced in Asian regions, especially in underdeveloped areas [29–33]. Additionally, the COVID-19 pandemic has further increased the healthcare burden [34]. These problems have significantly hindered the implementation of CR. Therefore, finding an adjunctive treatment that is beneficial for cognitive function and has low healthcare burden is of great importance.

Mahjong is a popular social entertainment form in China with a gambling nature that requires attention, information processing, visuomotor coordination, and social interaction, and it is closely associated with cognitive improvement [35–40]. This repetitive cognitive exercise can improve executive function [41], verbal memory [42], attention [43] and eye-hand coordination [44] in the elderly. Otherwise, the higher frequency of playing Mahjong is associated with improved cognitive function and self-coordination abilities [45]. Importantly, Mahjong does not require professional medical personnel for guidance and participation; it can be organized and maintained by the players themselves, reducing the healthcare burden [42]. On the other hand, Mahjong, as a form of social participation, plays a role in increasing interpersonal communication, social support, and promoting mental health [46–50], which helps alleviate stress-related neuronal changes and improve cognitive function [51, 52].

Objective

This study reports a preliminary randomized controlled trial testing the hypothesis that long-term Mahjong intervention in the daily lives of patients with schizophrenia can improve their cognitive function and quality of life.

Study design

This pilot, single-blind, randomized controlled trial was approved by the Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Approval Number: 2024-010-02) and registered with the China Clinical Trials Center (Registration Number: ChiCTR2400080268, date: 2024-01-25). Figure 1 represents the research procedure schematically.

Participants were randomly assigned to 2 groups. The intervention group received Mahjong combined with standard treatment, while the control group received only standard treatment. During the study, the type and dosage of medication for patients were not adjusted. Due to the nature of the intervention, instructors and participants could not be blinded to the group assignments. To minimize potential bias, assessors and data analysts were kept unaware of the intervention groups throughout the study.

Participants

Participants were recruited from the Department of Psychiatry, Yubei District Hospital of Traditional Chinese Medicine, Chongqing, and lived long-term in the inpatient department, with relatively uniform schedules and had sufficient time to play Mahjong.

Patients over 18 years old, with sufficient abilities to complete Mahjong and cognitive function tests, meeting DSM-5 criteria for schizophrenia, having stable conditions, and a total PANSS score of less than 60 were recruited. Patients with severe physical illnesses, organic brain diseases, a history of head trauma, a history of substance abuse, as well as those who were manic, impulsive, or uncooperative were excluded. 58 participants expressed interest, but 3 participants were excluded during the screening process, and 6 withdrew consent. As the trial was conducted in the male patient ward, female patients were not included in this study. After the patients and their families signed informed consent forms, a total of 49 patients were recruited.

Assessment

Assessments were conducted at patient enrollment (T0), and at the fourth week (T1), eighth week (T2), and twelfth week (T3) after enrollment.

Cognitive function

To assess cognitive changes, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was employed, which is a tool previously demonstrated to be highly sensitive in evaluating the cognitive function of schizophrenia [53, 54].

1. Reaction time (RTI) measure the subject’s speed of response to a visual target where the stimulus is either predictable (simple reaction time) or unpredictable (choice reaction time). The outcome measures include accuracy score, reaction time and movement time.

2. Spatial working memory (SWM) assesses the subject's ability to retain and manipulate spatial information in working memory. The outcome measures include between errors and strategy employed. A high strategy score represents poor use of strategy, and a low score equates to effective use.

3. Paired associates learning (PAL) assesses visual memory and new learning. The outcome measures include number of errors.

Clinical outcome

Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) [55]. Otherwise, the Self-report Quality of Life Measure for People with Schizophrenia (SQLS) was used to evaluate patients’ quality of life [56]. In data analysis, patients' medication regimens were converted to equivalent doses of olanzapine for comparison [57].

Intervention

Considering that repetitive and prolonged cognitive remediation can produce greater cognitive benefits [24, 28], the intervention group engaged in cognitive training through Mahjong for 2 hours per day, 4 days per week for 12 weeks. During the trial, researchers reminded and arranged for players, and subjects could also organize their own Mahjong sessions.

Mahjong is typically played by four participants seated at a square table, representing the compass points of east, south, west, and north. The game utilizes a set of 144 tiles, with each player initially dealt thirteen tiles from the tile wall, while the dealer, seated in the east position, receives fourteen tiles. The objective of the game is to create a winning hand consisting of four sets of three tiles and a pair of tiles of the same suit, totaling fourteen tiles. The sets can comprise either three identical tiles (known as a “pung”) or three consecutive tiles in the same suit (known as a “chow”). Victory is achieved when a player forms a complete hand and declares “Mahjong”. This declaration signals the end of the game, and the winning player reveals their hand to calculate points based on the hand's complexity and any predetermined scoring rules. Due to the patients' cognitive impairments, we chose the simplest Mahjong rules, where the suits only consist of three types: bamboos, characters, and dots. Detailed rules can be found in The Mahjong Guide – Mahjong games, information and other resources (the-Mahjong-guide.com).

Statistical analysis

Data analysis was conducted using SPSS 25.0 statistical software. Quantitative data were expressed as mean ± SD if approximately normally distributed, otherwise as median and IQR. Intention-to-treat (ITT) analysis was conducted with all randomly assigned participants included in the analysis. Continuous variables were compared using Student's t-test or Mann-Whitney U test. Considering the non-independence of data and the non-normal distribution of some outcomes, Generalized Estimating Equation (GEE) model was applied. During the modeling process of the GEE, interaction terms between time and group were introduced. For the cognitive outcome, adjustments were made for age, education, disease duration, dose equivalents for olanzapine, PANSS total score, and their respective baseline results. For clinical outcomes, adjustments were made for age, educational level, disease duration. P-value of less than 0.05 was considered statistically significant.

To address missing data in our study, Last Observation Carried Forward (LOCF) and Complete Case Analysis were employed. To assess the robustness of our data analysis, we performed GEE analysis on both the LOCF and complete case datasets and compared these results with those from the ITT dataset. All covariates used in the analyses remained unchanged across different datasets.

Baseline characteristics of participants

Participants in the intervention and control groups did not differ in cognitive function and demographic characteristics (Table 1).

Table 1. Baseline demographic, cognitive and clinical characteristics of participants.
Variable	Intervention (n=24)	Control (n=25)		P value
Age, years ^a	42.3 (8.2)		44.7 (7.5)	0.301
Education, years ^b	8.5 (3.0)		9.0 (1.0)	0.395
Duration of disease, years ^a	17.4 (6.3)		19.2 (7.0)	0.355
Antipsychotic drug doses, mg/d ^{b c}	8.0 (8.4)		9.8 (5.8)	0.703
PAL Total errors (adjusted) ^b	48.0 (78.0)		67.0 (44.0)	0.167
PAL Total errors (6 shapes, adjusted) ^b	16.5 (37.0)		28.0 (23.0)	0.207
SWM Between errors ^b	44.5 (40.0)		64.0 (28.0)	0.211
SWM Strategy ^b	40.0 (10)		43.0 (8.0)	0.434
RTI Simple accuracy score ^b	14.1 (1.0)		14.3 (0.8)	0.948
RTI simple reaction time ^b	457.7 (217.9)		485.7 (189.6)	0.631
RTI simple movement time ^a	654.6 (191.9)		697.4 (187.9)	0.435
RTI Five-choice accuracy score ^b	14.0 (2.0)		14.0 (2.0)	0.958
RTI Five-choice reaction time ^b	517.5 (209.1)		539.5 (211.3)	0.841
RTI five-choice movement time ^a	729.4 (170.6)		737.3 (181.0)	0.876
Total SQLS score ^a	53.3 (10.6)		48.2 (13.3)	0.141
Total PANSS score ^a	48.8 (5.3)		50.0 (6.1)	0.478

PANSS Positive and Negative Syndrome Scale, SQLS Self-report quality of life measure for people with schizophrenia

^a mean (SD), ^b median (IQR),

^c all antipsychotic doses were appropriately converted to olanzapine doses [57]

Cognitive function outcomes

Compared to baseline (T0), the intervention group showed significant reduction in RTI simple reaction time and five-choice reaction time. Specifically, at T3, the RTI simple reaction time decreased from 592.58 ms (SE 34.07) at baseline to 425.91 ms (SE 30.36), and the five-choice reaction time decreased from 553.33 ms (SE 37.36) at baseline to 460.82 ms (SE 30.52). Similarly, the intervention group exhibited significant reduction in RTI movement time. At T3, the RTI simple movement time decreased from 654.61 ms (SE 38.34) at baseline to 544.76 ms (SE 27.54), and the five-choice movement time decreased from 729.39 ms (SE 34.10) at baseline to 604.34 ms (SE 32.24). The RTI simple accuracy score of the intervention group improved to 14.50 (SE 0.20) at T3, compared to 14.37 (SE 0.37) for the control group, showing a significant group effect. Additionally, compared with baseline, the PAL total errors decreased from 68.46 (SE 11.38) to 64.01 (SE 10.10) at T3. However, in the other SWM tests, GEE analysis did not reveal any significant time, group, or group-by-time interaction effects between the intervention and control groups (Table 2).

Clinical outcomes

Compared to baseline (T0), the intervention group showed significant improvements in SQLS over time, as indicated by the significant group-by-time interaction effects and time effects. At T3, the SQLS total scores were 45.92 (SE 2.59) for the intervention group and 50.01 (SE 3.04) for the control group. No significant differences were observed in PANSS between the intervention and control groups (Table 2).

Sensitivity Analysis

During the study, 8 patients dropped out, while 41 patients completed the trial. Comparing the baseline characteristics between dropout and completer patients revealed that dropout patients were older (50.88 years vs. 42.10 years, p＜0.001), had a longer duration of illness (22.38 years vs. 17.54 years, p = 0.001). We conducted a sensitivity analysis using the LOCF and complete case datasets with GEE. The covariates remained consistent with those used in the original ITT analysis. The results indicated that the statistical significance of the group-by-time interaction, time effect, and group effect were consistent across the ITT, LOCF, and complete case datasets, demonstrating the robustness of our primary findings.

Table 2. Primary and Secondary Outcomes
Outcome	Intervention (n=24)	Control (n=22)	Group-by-Time Interaction Effect		Time effect		Group effect
			Wald χ2	P	Wald χ2	P	Wald χ2	P
RTI Simple accuracy score (SE)			8.176	0.043	4.810	0.186	3.281	0.070
T0	14.17 (0.20)	14.20 (0.17)
T1	14.33 (0.16)	13.46 (0.27)
T2	14.19 (0.19)	13.62 (0.31)
T3	14.36 (0.20)	14.03 (0.36)
RTI simple reaction time (SE), ms			18.162	＜0.001	9.161	0.027	1.646	0.199
T0	492.58 (34.07)	515.75（33.37）
T1	484.71（51.53）	511.67（29.47）
T2	463.34（33.23）	561.97（47.51）
T3	425.91（30.36）	533.17（40.41）
RTI simple movement time (SE), ms			15.532	0.001	36.071	＜0.001	2.695	0.101
T0	654.61（38.34）	697.36（36.81）
T1	613.22（29.80）	653.51（33.81）
T2	594.79（32.68）	675.71（28.00）
T3	544.76（27.54）	662.90（32.84）
RTI Five-choice accuracy score (SE)			1.554	0.670	5.669	0.129	0.725	0.394
T0	13.88（0.18）	13.84（0.19）
T1	13.96（0.23）	13.50（0.32）
T2	14.09（0.31）	13.92（0.26）
T3	14.22（0.32）	13.91（0.28）
RTI five-choice reaction time (SE), ms			19.944	＜0.001	11.184	0.011	0.729	0.393
T0	553.33（37.36）	545.26（31.87）
T1	539.98（56.30）	543.96（30.07）
T2	509.36（34.56）	583.59（41.38）
T3	460.82（30.52）	561.85（42.81）
RTI five-choice movement time (SE), ms			24.436	＜0.001	34.482	＜0.001	0.858	0.354
T0	729.39（34.10）	737.25（35.47）
T1	683.17（30.71）	686.87（34.61）
T2	667.91（37.42）	717.36（31.72）
T3	604.34（32.24）	710.93（36.09）
SWM Between errors (SE)			4.828	0.185	3.717	0.294	3.460	0.063
T0	48.50 (4.77)	56.92 (4.03)
T1	45.13 (4.74)	58.87 (4.54)
T2	45.34 (4.70)	56.87 (4.30)
T3	44.93 (4.27)	56.43 (4.31)
SWM Strategy (SE)			5.722	0.126	1.003	0.800	0.030	0.862
T0	38.17 (1.56)	39.52 (1.68)
T1	39.13 (1.42)	37.81 (1.75)
T2	38.88 (1.31)	39.03 (1.86)
T3	38.40 (1.28)	39.64 (1.70)
PAL Total errors (adjusted) (SE)			2.834	0.418	8.234	0.041	0.496	0.481
T0	68.46 (11.38)	75.60 (8.83)
T1	63.29 (10.47)	75.59 (8.81)
T2	62.09 (9.51)	71.59 (9.31)
T3	64.01 (10.10)	73.60 (9.67)
PAL Total errors (6 shapes, adjusted) (SE)			0.532	0.912	4.067	0.254	0.770	0.380
T0	25.25 (3.61)	29.60 (2.73)
T1	25.00 (3.60)	28.45 (2.83)
T2	24.47 (3.22)	27.86 (2.79)
T3	24.28 (3.26)	28.06 (3.04)
SQLS total score (SE)			12.042	0.007	23.847	＜0.001	0.008	0.931
T0	53.34（2.11）	48.20（2.60）
T1	49.30（2.35）	47.41（2.68）
T2	44.11（2.26）	45.97（2.98）
T3	43.30（2.17）	47.38（2.76）
PANSS total score (SE)			7.518	0.057	1.754	0.625	1.239	0.266
T0	48.83（1.06）	50.00（1.19）
T1	48.04（1.03）	51.17（1.28）
T2	49.31（1.19）	50.80（1.28）
T3	49.13（1.03）	50.25（1.30）

PANSS Positive and Negative Syndrome Scale, SQLS Self-report quality of life measure for people with schizophrenia

To the authors’ knowledge this is the first randomized controlled trial aimed at exploring the effects of prolonged Mahjong intervention on cognitive function in patients with schizophrenia. Over time, the intervention group showed improvements in reaction time and movement time of response to a visual target, associative learning and short-term visual memory. Moreover, the quality of life of schizophrenia patients also improved during the Mahjong intervention.

Previous research indicates that playing Mahjong can provide cognitive benefits for the elderly [58] and is associated with a slower decline in cognitive function [45, 59]. Even among individuals already diagnosed with dementia, Mahjong can yield cognitive benefits, and these effects persist for up to a month after stopping the activity [42]. Additionally, similar to other cognitive games, playing Mahjong involves various cognitive functions. Participants need to analyze and strategize based on the information they receive, followed by logical operations, thus gaining cognitive training in the process [60, 61]. Our study found that after long-term Mahjong intervention, schizophrenia patients showed significant improvement in reaction time, consistent with previous research indicating that Mahjong can enhance attention [43]. Mahjong requires attentional control to quickly identify and remember visual information, while patients' eye-hand coordination is repeatedly trained [44], ultimately leading to improvements in specific cognitive functions.

Research has also preliminarily explored the brain changes induced by Mahjong. For instance, during Mahjong, an increase in oxygenated hemoglobin concentration in language-related cortical areas has been observed [62], and identifying Mahjong tiles by touch activates the player's bilateral sensorimotor cortex [63]. Similarly, in experts who have played shogi (Japanese chess) for a long time, neural response times in the frontal and temporal lobes are significantly shortened, allowing quicker reactions to global and local cognitive information [64]. Additionally, early studies have found that repetitive motor tasks in healthy individuals can lead to motor cortex activation and behavioral improvements [65]. Like other cognitive activity, in processing complex information such as in Mahjong, the brain utilizes neurons distributed across multiple processing levels and regions to complete relevant perceptual and cognitive inputs and action outputs [66]. This type of board game appears to meet the three key points of neuroscience-informed cognitive training methods, namely enhancing perceptual processes, ensuring intensive and adaptive training schedules, and engaging the brain's reward and attention systems [66]. These factors might explain why long-term Mahjong intervention improves cognitive function in schizophrenia patients.

In addition to cognitive impairments and clinical symptoms, social isolation can significantly impact patients' quality of life [67]. Mahjong, as a group social recreational activity, is often associated with better quality of life in healthy populations [50, 68]. Participation in recreational activities can also benefit people with psychosis [69], and the frequency of participation is positively correlated with better quality of life [70]. Previous studies have shown that Mahjong can reduce depressive symptoms in patients with mild dementia [40], and most psychosocial interventions can improve the quality of life for patients [71]. In this trial, we found that patients showed improvements in SQLS after participating in long-term Mahjong intervention. This improvement could be because leisure activities impart their mental health benefits by increasing individuals’ perception of spending their time effectively [72]. In addition, as the social motivation theory suggests, humans are driven by the need to belong and be socially connected. When schizophrenia patients engage in Mahjong, their fundamental psychological needs are met, which can enhance overall well-being and happiness.

Given that schizophrenia patients' cognitive function and brain structure deteriorate over time [73, 74]. Early prevention of progressive cognitive decline in schizophrenia patients may be necessary [75]. However, due to economic and resource constraints, priority and awareness issues, personalization and suitability deficiencies, and the lack of implementation context and evidence, CR struggles to become a routine cognitive treatment method [25]. Therefore, before CR can be widely implemented, incorporating board games like Mahjong, which have cognitive training and social attributes, low medical burden, and can be conducted independently by patients, into the daily activities of schizophrenia patients seems to have potential benefits, especially for long-term hospitalized patients.

The lack of significant improvement in certain cognitive domains when comparing the two groups could be due to the intensity and specificity of cognitive training required for these complex functions [76], which may not be fully addressed by playing Mahjong. Therefore, cognitive training that does not specifically target working memory, is unlikely to produce significant transfer effects [77]. Additionally, reduced gray matter volume [78], white matter disruptions [79] and excessive synaptic deficits [80] collectively contribute to the limited efficacy of Mahjong interventions.

Limitation

As a pilot trial, several limitations should be acknowledged. Firstly, this was a single-center study with a small sample size. The findings may not be representative of the population of patients with different state of schizophrenia. Secondly, due to practical constraints, our study included only male patients. This gender-specific sample may introduce a bias and limit the applicability of our findings to female patients. Previous research has shown that gender differences can influence cognitive function in schizophrenia [81]. Thirdly, our sample predominantly consisted of patients with long disease durations and older age. Chronicity and age can significantly impact cognitive function and plasticity, potentially affecting the responsiveness to cognitive interventions [82]. Lastly, patients who showed an interest in Mahjong were enrolled. This selection criterion could introduce a self-selection bias, as patients who are naturally inclined towards engaging in such cognitive activities might already have better baseline cognitive function or motivation, potentially skewing the results.

In conclusion, while this pilot study suggests that prolonged Mahjong training may benefit certain cognitive functions and quality of life in patients with schizophrenia, further research with larger, more diverse samples and longer follow-up periods is necessary to confirm and extend these findings.

CANTAB: Cambridge Neuropsychological Test Automated Battery; CR: Cognitive remediation

GEE: Generalized Estimating Equation; ITT: Intention-to-treat; LOCF: Last Observation Carried Forward; PAL: Paired associates learning; PANSS: Positive and Negative Syndrome Scale; RTI: Reaction time; SQLS: Self-report Quality of Life Measure for People with Schizophrenia; SWM: Spatial working memory.

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Approval Number: 2024-132-01). All participants provided written informed consent prior to their inclusion in the study.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Competing interests

There is no conflict of interest to report related to this work.

Funding

This study was supported by the Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0107). The funders played no part in shaping the study's design, data gathering, data analysis, data interpretation, or manuscript composition.

Authors' contributions

RQH and ZLX contributed to the study's conceptualization, design, and manuscript writing. YWG and JTL managed the database. JYL and HRL conducted the statistical analysis. RQH prepared the initial manuscript draft. All authors participated in manuscript revisions, and reviewed and approved the final submitted version. QHL supervised the research progress, coordinated collaboration, contributed to manuscript revisions, and secured funding and resources.

Acknowledgements

We thank the medical staff of Yubei District Hospital of Traditional Chinese Medicine for their support and coordination during the data collection process. We also thank the patients' families for their consent and support of this study.

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A Study on Mahjong Intervention to improve Cognitive Impairment in Patients with Schizophrenia: a pilot, single-blind, randomized, controlled trial

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