week 6 bio

Schizophrenia Research 262 (2023) 112–120

Available online 8 November 2023 0920-9964/© 2023 Elsevier B.V. All rights reserved.

Effects of physical activity and nutrient supplementation on symptoms and well-being of schizophrenia patients: An umbrella review

Houda El Kirat a,b,c,*, Asmaa Khattabi a,b, Mohammed Khalis b, Zakaria Belrhiti a,b

a Public Health and Management Department, International School of Public Health, Mohammed VI University of Health and Sciences, UM6SS, Casablanca, Morocco b Mohammed VI Center for Research and Innovation, CM6RI, Rabat, Morocco c National School of Public Health, Ministry of Health, and Social Protection, Morocco

A R T I C L E I N F O

Keywords: Umbrella review Systematic reviews Physical activity Nutrition Diet Schizophrenia

A B S T R A C T

Background: Physical activity and nutrient supplementation have been acknowledged to have moderate effects on symptoms and treatment compliance of patients suffering from mental disorders. However, there is still a lack of consensus on whether these interventions are effective on schizophrenia clinical and quality of life outcomes. Our objective was to provide a comprehensive review of systematic reviews that addressed the effects of physical activity and nutrient supplementation on treatment compliance, symptoms and improving the well-being of patients with schizophrenia. Method: We carried out an umbrella review following Johanna Briggs Institute methodological guidance as follows: 1) Formulating a review question, 2) developing a search strategy, 3) systematic search in scientific databases (Medline, Cochrane Library, Science Direct), 4) study selection (title, abstract and full-text screening), 5) data extraction, 6) data charting and synthesis and 7) quality appraisal. Results: Our search strategy yielded 2214 articles published between 1960 and 2023. Nine systematic reviews fitted our inclusion criteria. Our umbrella review suggests that yoga is effective on positive and negative symptoms, and well-being, whereas aerobics is only effective on positive symptoms. We also found that sup- plementing polyunsaturated fatty acids and trace elements reduced schizophrenia’s negative symptoms. Conclusion: Our umbrella review highlighted moderate to low-quality evidence supporting the effectiveness of physical activity on negative and positive schizophrenia symptoms and the overall well-being of patients with schizophrenia. Our review findings support the need to promote physical activity and supplementation of micronutrients, a cost-effective strategy to promote healthy lifestyles in low and middle-income countries.

1. Introduction

Schizophrenia is a chronic mental illness affecting 24 million people (Hjorthøj, Stürup, McGrath, & Nordentoft, 2017). In 2016, schizo- phrenia was ranked among the top 15 leading causes of disability worldwide (Vos et al., 2016). It is considered the eighth primary cause of disability in young adults aged between 15 and 44 years. Schizophrenia has a lifetime prevalence estimated at 4 per 1000 (Ayano et al., 2019; Moreno-Küstner et al., 2018; Saha et al., 2005).

Despite being a low-prevalence disease (Baxter et al., 2013), schizophrenia is responsible for 0.6 % of disability-adjusted life years and decreased quality of life. It is also responsible for a significant economic and social burden (between 0.02 % to 1.65 % of gross

domestic product (GDP)) (Moreno-Küstner et al., 2018) (Chong et al., 2016; He et al., 2020; IHME, 2022; Németh et al., 2018). Schizophrenia is responsible for high medical and social costs estimated at 1.69 per 1000 GDP, judicial and imprisonment costs (0.49 per 1000 GDP), loss of productivity (15.9 per 1000 GDP) in addition to family informal care cost (2.48 per 1000 of GDP) (Charrier et al., 2013).

The diagnosis of schizophrenia requires qualified specialized pro- fessionals to identify a complex set of symptoms, including cognitive impairment, disorganization, and negative and positive symptoms (Guelfi et al., 2021). These symptoms are well-defined in international disease classifications such as the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) (American Psychiatric, 2021; American Psychiatric Association and Association, 2013) and the International Classification of Diseases (ICD-11) (WHO, 2022).

* Corresponding author at: Public health and management department, International School of Public Health, Mohammed VI University of Health and Sciences, UM6SS, Casablanca, Morocco.

E-mail address: [email protected] (H. El Kirat).

Contents lists available at ScienceDirect

Schizophrenia Research

journal homepage: www.elsevier.com/locate/schres

https://doi.org/10.1016/j.schres.2023.10.021 Received 7 February 2023; Received in revised form 21 October 2023; Accepted 22 October 2023

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The clinical management of schizophrenia is challenged by special- ized staff availability, the high cost of psychotherapy sessions, the low efficacy of psychotropic drugs on negative symptoms, side effects and poor therapeutic compliance (Citrome & Vreeland, 2008; Jones, Hacker, Cormac, Meaden, & Irving, 2012; Kelley & Kelley, 2015; Kittel- Schneider & Reif, 2016; Malchow et al., 2013; Ruddy & Dent-Brown, 2007; Ruddy & Milnes, 2005).

Recently, promising evidence suggested that physical activity (Firth, Cotter, Elliott, French, & Yung, 2015; Stanton & Happell, 2014; Van- campfort, Knapen, et al., 2012; Vancampfort et al., 2014, 2017; Van- campfort et al., 2012a; Vancampfort et al., 2012b) and nutriment supplementation (Irving et al., 2006; Peet, 2003) are effective on reducing positive and negative symptoms and psychotropic side effects (Faulkner et al., 2021; Mukundan et al., 2010) while being cost-effective and a feasible intervention (Bernard and Ninot, 2011). To our knowl- edge, there is still limited documentation summarizing existing evidence on the effect of physical activity and nutrients on schizophrenia (Faulkner et al., 2022).

To fill this gap, we conducted a systematic umbrella review, a sys- tematic review of systematic reviews, that addressed the effect of physical activity and supplementation of micronutrients on the reduc- tion of schizophrenia symptoms, cognitive impairments, and the well- being of patients.

2. Material and methods

We adopted the umbrella review methodology (Aromataris et al., 2015; Grant and Booth, 2009; Worswick et al., 2013) that proved appropriate in synthesizing the effectiveness of a broad range of het- erogeneous interventions addressing the same health problem. In prac- tice, this umbrella review was carried out in line with the Joanna Briggs methodological guidance (Aromataris et al., 2015) and the Prisma Checklist reporting guidelines (Page, 2021)

2.1. Specifying the review question

We developed the following review question: What is the effect of physical activity and nutrient supplementation on symptoms and the well-being of adults with schizophrenia?

Our review question is structured using the following PICO frame- work (Population, Intervention, Comparison, Outcome) as suggested by (Peters et al., 2015) and (Higgins et al., 2019).

Population (P): Patients with a diagnosis of schizophrenia accord- ing to the DSM-IV or DSM-V classification manual, aged over 18 years. Interventions (I): 1) Physical activity is a voluntary motor activity with a level of

energy expenditure beyond the threshold of sedentariness and

loss of autonomy (Page et al., 2021). We did not distinguish be- tween types of physical activity (jogging, climbing…etc.).

2) Nutrient supplementation is defined as any form of diet. Comparison (C): Control groups include patients with schizo- phrenia treated with the standard clinical therapeutics. Outcome (O): We defined the primary outcomes as the main clinical diagnosis criteria for schizophrenia included in the DSM V (APA, 2013) and ICD_10 and ICD_ classifications (International Classifica- tion of Diseases) (WHO, 2022) in line with other studies(Keefe et al., 2008):

2.1.1. Primary outcomes O1: Disappearance of positive symptoms:. Delusional ideation, con-

ceptual disorganization, hallucinatory activity, excitement, and ideas of greatness, distrust, persecution, and hostility.

O2: Improvement of negative symptoms: Blunted expression of emotion, emotional withdrawal, poor contact, passive/apathetic social withdrawal, difficulty with abstraction, lack of spontaneity and fluency in conversation, and stereotyped thinking.

O3: General/psychological well-being: Somatic preoccupation, anx- iety, guilt, tension, mannerism and posture disorder, depression, psy- chomotor slowing, lack of cooperation, disorientation, lack of attention, lack of judgment and awareness of the illness, volitional disorder, poor impulse control, excessive self-preoccupation, active social avoidance.

O4: Dyskinesia related to psychotropic treatments.

2.1.2. Secondary outcomes O5: Cognitive functioning: Following recent evidence on the potential

effects of intense physical exercise on the cognitive functioning of pa- tients with schizophrenia (Firth et al., 2017a; Gebreegziabhere et al., 2022), we included cognitive functioning as a secondary outcome.

2.2. Systematic searches

We searched three international databases (Medline, Science-direct and Cochrane Library) for published papers between 1960 and 2023. For Medline, we used the following search strategy: "physical activity, Diet, Nutrition, Lifestyle, Schizophrenia, ((Schizophrenia) AND ((((((physical activity) OR "Exercise/therapeutic use" [Majr]) OR "Diet" [Mesh]) OR "Nutrition Therapy" [Mesh]) OR "Life Style"[Mesh]) AND Review[ptyp]))". To manage references, we used Mendeley reference management software.

2.3. Study selection

The first and last author performed the study selection. No disagreement between the reviewers was reported. Inclusion and exclusion criteria are presented in Box 1.

We included systematic reviews (SR) that addressed our PICO framework mentioned above. We included exclusively systematic re- views of randomized control trials (RCTs), considered the gold standard form of evidence about effective interventions (Bothwell, Greene, Podolsky, & Jones, 2016; Hariton and Locascio, 2018). See Box 1:

2.4. Systematic data extraction and synthesis

We used systematic data charting form for interventions as defined in the Cochrane Handbook for systematic reviews see Box 2. Data extrac- tion was performed by the first author and checked by the last author.

2.5. Quality appraisal

Quality appraisal of included systematic reviews was carried out by two independent researchers (HE, ZB) using the updated AMSTAR 2 checklist (Shea et al., 2017). The AMSTAR 2 checklist is comprised of

Abbreviations

AMSTAR a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions,

DSM Diagnostic and Statistical Manual ICD International Classification of Disease PICO Population, Intervention, Comparison, Outcome RCT Randomized controlled trial RoB Risk of bias tool RR Relative Risk SMD Standards mean difference WHOQOL-BREF World Health Organization Quality of Life-BREF

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sixteen items with critical and non-critical bias criteria. The overall quality of each systematic review is assessed using the four following grading categories: High quality: no or one non-critical weakness; Mod- erate: More than one non-critical weakness; Low: Only one critical flaw; Critically low: More than one critical flaw with or without non-critical flaws.

3. Results

In the following section, we will present the general characteristics of included studies and a summary of evidence about the effectiveness of physical activity and nutrient supplementation on positive, negative, and cognitive impairment in patients with schizophrenia. We finally present the overall quality appraisal of evidence in included reviews. We suggest practical and policy implications for psychiatric and medical social practice, health policy, and system research.

3.1. Study selection

We identified 2214 articles. Fig. 1 represents the different steps of study selection according to the standards for reporting standards for systematic reviews and meta-analysis (PRISMA) (Stovold et al., 2014). After title and abstract screening, we retained sixty-six papers for full- text selection. Only nine systematic reviews were included (see excluded studies with reasons of exclusion in Appendix 1).

3.2. Study characteristics

The nine included studies were published between 2006 and 2023 (Broderick et al., 2015; Firth et al., 2017a; Firth et al., 2017b; Irving et al., 2006; Kim et al., 2023; Ren and Xia, 2013; Sabe et al., 2020; Vancampfort et al., 2012a; Vancampfort et al., 2012b).

We identified four systematic reviews without meta-analysis (two

reviews of yoga interventions (Broderick et al., 2015; Vancampfort et al., 2012b), one review of aerobic and strength training (Vancampfort et al., 2012a), one review of polyunsaturated fatty supplementation) (Irving et al., 2006) and five systematic reviews with meta-analysis (Dance therapy (n = 1) (Ren and Xia, 2013), vitamins, antioxidants and trace elements supplementation (n = 1) (Firth et al., 2017b) and physical activity including aerobic and non-aerobic exercises (n = 3) (Firth et al., 2017a; Kim et al., 2023; Sabe et al., 2020).

Included systematics reviews comprising 90 primary studies and a total of 448,029 patients. Physical activity interventions are heteroge- neous. They include a broad range of interventions (Yoga (Vancampfort, Knapen, et al., 2012; Broderick, Knowles, Chadwick, & Vancampfort, 2016), dance therapy (Ren and Xia, 2013), Aerobic physical therapy, strength training aerobics and stretching (Vancampfort et al., 2012a; Sabe et al., 2020; Firth et al., 2017a; Kim et al., 2023; Sabe et al., 2020)). No heterogeneity measures were reported in included reviews.

Only two reviews addressed nutrient supplementation. They comprise supplementation with polyunsaturated fatty acids (Irving et al., 2006) and with vitamins, antioxidants and trace elements (zinc and cobalamine) (Firth et al., 2017a, 2017b) (see Tables 1 and 2).

3.3. Effects on schizophrenia symptoms

3.3.1. Positive symptoms Four reviews reported beneficial effects of yoga sessions, physical

exercise and supplementation of micronutrients on the reduction of positive symptoms (Vancampfort et al., 2012a) (24, 28, 35) (see Tables 3 and 4). Interventions with statistically significant effects are: two in- terventions with aerobic exercises (SMD (standard median difference) SMD, − 0.27; 95 % CI, − 0.46 to, − 0.09; p = 0.004) (Sabe et al., 2020) and basic body awareness exercises (no effect size, 3 out of 4 RCT with significant positive effects) (Vancampfort et al., 2012a) and Yoga (RCT, n:83, RR 0.70 CI 0.55 to 0.88) (Broderick et al., 2015). Other studies

Box 1 Inclusion and exclusion criteria.

Inclusion criteria: Compliance with the PICO framework. Systematic review of RCTs. Exclusion criteria: Other types of reviews: narrative reviews, systematic reviews of other study designs such as cross-over randomized trial, cross-sectional, prevalence, ecological studies, cohort studies, time series. Reviews addressing other outcomes such as somatic effects related to schizophrenia (e.g., obesity, and metabolic syndrome). Reviews addressing other mental disorders. Primary articles.

Box 2 Data extraction chart.

Author, Year, Systematic review objectives. Databases. Type of intervention (Physical activity or nutrition supplementation). Characteristics of the intervention (frequency, component, time to follow up, participants). Number of included studies in systematic review. Effects and outcomes measures (Relative risk, Odds Ratios, Standard mean differences (SMD).

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suggested that combining dietary zinc supplementation with vitamin B has beneficial effects on schizophrenia positive symptoms and that zinc supplementation alone has a significant effect on positive symptoms (p = 0.04) (Firth et al., 2017a, 2017b).

3.3.2. Negative symptoms Our review shows that yoga, dance therapy and aerobic physical

activity were reported to have a positive effect on the reduction of negative symptoms. Our findings suggest that yoga interventions allow a reduction of 17 % and 37 % of negative symptoms (Vancampfort et al., 2012a). Our review also shows that dance therapy is associated with significant statistical reduced relative risk (1 RCT, n: 83, RR 0.70, CI 0.55 to 0.88) and associated 20 % improvement of negative symptoms compared to control groups (Ren and Xia, 2013). Additionally, our umbrella review shows that aerobic physical activity is associated with reduced relative risk of negative symptoms (1 RCT, n = 45, RR 0.62, 95 % CI 0.39 to 0.97) (Ren and Xia, 2013) and a standardized mean dif- ference of − 0.24 (95 % CI − 0.43 to − 0.06; p = 0.01) (Sabe et al., 2020).

In contrast, two included systematic reviews (Irving et al., 2006; Vancampfort et al., 2012b) have shown that polyunsaturated fatty acid supplementation and physical exercise have no effect on negative symptoms of schizophrenia.

Some scholars (Firth et al., 2017a, 2017b) suggested that the type of micronutrient is associated with different effectiveness levels. The combination of vitamin C, vitamin E, and zinc has a beneficial effect on the negative symptoms of schizophrenia. At the same time, no study has reported any effects of vitamin B or chromium (see Table 3).

3.3.3. General well-being Our review findings suggest that physical activity has positive effects

on the general well-being of patients with schizophrenia. Included re- views showed that yoga has a statistically significant effect (1 RCT, n =

Fig. 1. PRISMA flowchart.

Table 1 Summary of included reviews by type of intervention.

Intervention type No. of reviews

Period of publication

The median of included studies

Physical activity 7 Yoga (Broderick et al., 2015;

Vancampfort et al., 2012b) 2 1960–2011 6 (3;8)

Dance(Ren and Xia, 2013) 1 1960–2012 1 Physical exercise: aerobic,

strengthening (Firth et al., 2017a; Kim et al., 2023; Sabe et al., 2020; Vancampfort et al., 2012a)

4 1960–2023 12,5 (10;17;10)

Dietary supplementation 2 Vitamin (Firth et al., 2017b) 1 1960–2016 18 Unsaturated fatty (Irving et al.,

2006) 1 1986–2007 8

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83, RR 0.88 CI 0.77 to 1) on quality-of-life scores which resulted in an increase of quality of life scores in four subdimensions: 1) Physical (+16 % to +23 %), 2) Psychological (+32 % to +49 %), 3) Social (+29 % and

+65 %; 4) Environmental (+7 % to +19 %) (Vancampfort et al., 2012b).

3.3.4. Dyskinesia Three systematic reviews (Irving et al., 2006; Ren and Xia, 2013;

Vancampfort et al., 2012a) explored the effect of interventions on dyskinesia and found no beneficial effect of polyunsaturated fatty acid supplementation, exercise, or micronutrient supplementation on dyski- nesia. The overall effects reported in the nine systematic reviews are summarized in Table 4.

3.3.5. Cognitive dysfunction Only two reviews reported positive effects of physical activity on

cognitive impairment symptoms (Broderick et al., 2015; Firth et al., 2017a). This includes statistically significant improvement of overall cognitive function, particularly working memory. Whereas no statisti- cally significant differences were observed in regard to cognitive pro- cessing speed and verbal learning and memory (Firth et al., 2017b).

3.4. Quality assessment

To assess the methodological quality of included reviews, we used the updated AMSTAR 2 checklist developed by (Shea et al., 2007) (see Table 5). All reviews used a well-defined search strategy and considered the risk of bias (RoB) in discussing their results and the overall quality of included primary studies. Six out of seven reviews assessed publication bias and its impact on review findings. Only four systematics reviews had previously published a systematic review protocol. With the exception of Sabe et al. (2020), all included systematic reviews have at least one critical flaw. Therefore, the overall confidence in the quality of evidence is between low and moderate quality evidence.

4. Discussion

This umbrella review aimed to summarize the effect of physical ac- tivity and nutrient supplementation on the symptoms and quality of life of patients with schizophrenia.

Our review highlighted the beneficial effects of vitamin C, vitamin E and zinc supplementation, yoga and dance therapy and aerobic exercise.

Table 2 General characteristics of included reviews.

Review ID (Author, Year)

Study objective Databases explored Study design

No of studies

Number of participants

(Irving et al., 2006)

Evaluate the effect of polyunsaturated fatty acid supplementation on the symptoms of schizophrenia

CINAHL, EMBASE, (RCT) 8 517

(Vancampfort et al., 2012b)

Assess the effectiveness of yoga on schizophrenia symptoms

EMBASE, PsycINFO, PubMed, ISI Web of Science, CINAHL, PEDro and Cochrane Library.

RCT 3 125

(Vancampfort et al., 2012a)

Assess the effectiveness of physical activity on schizophrenia symptoms

EMBASE, PsycINFO, RCT 10 322

(Ren and Xia, 2013)

Assess the effect of dance therapy on schizophrenia

Cochrane Schizophrenia Group, Chinese main medical databases RCT 1 45

(Broderick et al., 2015)

Assess effect of yoga on schizophrenia versus standard treatment

MEDLINE, PubMed, EMBASE, CINAHL, BIOSIS, AMED, PsycINFO, and registries of clinical trials

RCT 8 447

(Firth et al., 2017a, 2017b)

Evaluate the effect of vitamin and mineral supplementation on the symptoms of schizophrenia

Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, AMED

RCT 18 832

(Firth et al., 2017a)

Assessing the effect of exercise on global cognition and specific cognitive domains in people with schizophrenia

Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, AMED (Allied and Complementary Medicine) HMIC Health Management Information Consortium, Ovid MEDLINE, PsycINFO, Embase and Google Scholar

RCT 10 (7 are RCT)

383

(Sabe et al., 2020)

Evaluating the effect of physical exercise on schizophrenia negative symptoms

Medline, Embase, PsycARTICLES, PsycINFO, the Cochrane Database

RCT 17 954

(Kim et al., 2023) Assessing the effect of physical activity on positive and negative symptoms of schizophrenia

PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, and Web of Science and manual search on Google Scholar.

RCT 15 1642

RCT: Randomized controlled trial.

Table 3 Characteristics of interventions.

Revue Type of intervention dosage Duration Frequency

(Irving et al., 2006)

Omega3 and Omega 6 dietary supplementation

6 to 16 weeks Not reported

(Vancampfort et al., 2012b)

Yoga (only postures, breathing practices and relaxation were emphasized, no meditation included).

8 to 16 weeks 2 to 5 sessions a week (duration 45 min to 60 min)

(Vancampfort et al., 2012a)

Aerobics, exercise, muscle strengthening, relaxation; “asic body awareness exercises”

Between 1 session to 20, 25 or 45 min

1 to 7 times/ week for 20 and 60 min/session

(Ren and Xia, 2013)

Dance therapy 4 months

(Broderick et al., 2015)

Yoga (postures, breathing practices, relaxation, and in some studies, three minutes meditation exercises)

1 to 4 months 8 to 36 sessions (45 to 60 min/ session)

(Firth et al., 2017a, 2017b)

Vitamin B supplementation (2 mg/day to 1200 mg)

5 days to 24 weeks

Vitamin E (544 IU a day + vitamin C (1000 mg par jour)

16 weeks

Zinc: 150 mg per day 6 weeks Chromium 400 micro-G per day

12 weeks

(Firth et al., 2017b)

Aerobic exercise/resistance 4 to 24 weeks 2 to 4 sessions/ week (20 to 60 min/session)

(Sabe et al., 2020)

Physical exercise (non- aerobic and aerobic programs) and cognitive training

17 to 22 weeks

Mean exercise duration 25 min to 49 min

(Kim et al., 2023)

Aerobic exercise, neuromotor exercise, multicomponent exercise

8 to 32 weeks 1 to 7 sessions/ week (30 to 60 min/ session)

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Table 4 Effects of physical activity or nutrient supplementation on schizophrenia symptoms.

ID (Author, Year) Effect on schizophrenia symptoms

Positive symptoms Negative symptoms Well-being Dyskinesia

(Irving et al., 2006)

No effect Not reported Not reported No effect on dyskinesia

(Vancampfort et al., 2012b)

− 20 % to − 33 % reduction of positive symptoms

− 17 % to − 37 % reduction of negative symptoms

Significant increase of quality-of-life scores (WHOQOL- BREF): 1) Physical: +16 % and +23 %; 2) Psychological (+32 %) and +49 %); 3) Social by +29 % and +65 %; 4) Environmental (+19 %) and (+7 %)

Not reported

(Vancampfort et al., 2012a)

Significant effect on positive symptoms

Not reported Improved quality of life through yoga and decreased anxiety

No significant effect

(Ren and Xia, 2013)

No significant difference Significant positive effect (1 RCT, n = 43, MD − 4.40 95 % CI − 8.15 to − 0.65) 20 % reduction of negative symptoms vs control group (1RCT, n = 45, risk ratio (RR) 0.62 95 % CI 0.39 to 0.97).

No significant difference Not reported

(Julie Broderick et al., 2015)

Positive effect: RCT, n:83, RR 0.70 CI 0.55 to 0.88

Positive effect:1RTC, n:83, RR 0.70 CI 0.55 to 0.88

Quality of life: 1 RCT: N = 60, MD 15.50, 95 % CI 4.27 to 26.73. Increase of Social Occupational Functioning Scale, 1 RCT, n = 83), RR 0.88 CI 0.77 to1

Not reported

(Sabe et al., 2020)

Significant effect on positive symptoms (SMD [1], − 0.18; 95 % CI, − 0.34 to − 0.02; p = 0.03),

Significant effect on negative symptoms (SMD, − 0.24; 95 % CI, − 0.43 to − 0.06; p = 0.01)

Not reported Not reported

(Firth et al., 2017a, 2017b)

Vitamin B (3 studies): No effect (G = 0.26,95 % CI (0.24 to 0.76), p 0.31)

Vit B: No effects (g = 0.154, 95 % CI − 0.12 to 0.42, p = 0.26)

Not reported Not reported

No effect of Vitamin E + Vitamin C Positive effect of the combination of Vitamin E + Vitamin C.

Not reported No effect of vitamin E

Significant effect of Zinc Supplementation on positive symptoms (p = 0.04)

Significant effect of Zinc Supplementation (p = 0,02)

Significant effect, p = 0.03 Not reported

Table 5 Quality appraisal of included systematic reviews using updated AMSTAR checklist.

AMSTAR 2 Checklist adapted from (Shea,2017)

60 02

,g ni

v rI

t r of

p ma

cn aV,et al 2012b)

(Vancam pfor

t fort Probst et al 2012b)

Ren,2013

Broderick;20 15

Firth,2017a

Firth, 2017b

Sabe, 2020

Kim ,2023

1) Did the research ques�ons and inclusion criteria for the review include the components of PICO? NO YES YES YES YES YES YES YES YES

2) Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report jus�fy any significant devia�ons from the protocol? ***

NO NO YES YES YES NO YES YES YES

3)Did the review authors explain their selec�on of the study designs for inclusion in the review? YES YES YES YES YES YES YES YES YES

4) Did the review authors use a comprehensive literature search strategy? *** Par�al YES YES YES YES YES YES YES YES YES

5) Did the review authors perform study selec�on in duplicate? YES YES YES YES YES YES YES YES YES

6) Did the review authors perform data extrac�on in duplicate? YES YES YES YES YES YES YES YES YES

7) Did the review authors provide a list of excluded studies and jus�fy the exclusions? *** NO YES NO NO NO NO YES YES YES

8) Did the review authors describe the included studies in adequate detail? Par�al YES YES YES YES Par�al

YES YES YES Par�al YES YES

9) Did the review authors use a sa�sfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? *** YES NO YES Par�al

YES YES Par�al YES YES Par�al

YES YES

10) Did the review authors report on the sources of funding for the studies included in the review? YES NO NO NO NO NO NO NO NO

11) If meta-analysis was performed did the review authors use appropriate methods for sta�s�cal combina�on of results? *** YES NO NO YES Par�al

YES YES YES YES YES

12)If meta-analysis was performed, did the review authors assess the poten�al impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis? YES NO NO YES NO NO YES YES YES

13) Did the review authors account for RoB in individual studies when interpre�ng/discussing the results of the review? *** YES YES YES YES YES YES YES Par�al

YES YES

14)Did the review authors provide a sa�sfactory explana�on for, and discussion of, any heterogeneity observed in the results of the review? YES YES YES YES YES YES YES NO YES

15) If they performed quan�ta�ve synthesis did the review authors carry out an adequate inves�ga�on of publica�on bias (small study bias) and discuss its likely impact on the results of the review? *** YES YES YES YES YES NO YES YES YES

16)Did the review authors report any poten�al sources of conflict of interest, including any funding they received for conduc�ng the review? YES YES YES YES YES YES NO YES YES

Total number of cri�cal weaknesses 2 3 2 1 1 3 0 0 0 Total number of non-cri�cal weakness 3 2 2 1 2 2 1 2 1

OVERALL QUALITY OF THE EVIDENCE (*** Cri�cal items)

Cri�cally low

Cri�cally low

Cri�cally low Low Low Cri�cally

low High quality Moderate High

quality

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This was supported by a high-quality systematic review (Sabe et al., 2020). Our review findings support existing evidence on the positive effects of micronutrient supplementation on mental health (e.g. depression) (Ekong and Iniodu, 2021).

Our review findings also support that yoga posture, breathing and relaxation exercise (i.e. sessions of 45 min each for about 16 weeks are associated with significant improvement of positive and negative symptoms and the general well-being of patients living with schizo- phrenia (Ren and Xia, 2013; Sabe et al., 2020; Vancampfort et al., 2012b).

Furthermore, our review showed that most yoga interventions did not include a meditation component, except for Ikai et al. (2014) and Ikai et al. (2013) described in the Broderick et al. (2015) review. This stems from existing evidence on the negative effects of prolonged meditation on schizophrenia symptoms (Bangalore and Varambally, 2012; Dyga and Stupak, 2015; Sharma et al., 2022; Suchandra et al., 2021). Thus, yoga interventions need to be implemented by specialized skilled professionals aware of schizophrenia conditions (Suchandra et al., 2021).

On the other hand, yoga is considered a complementary treatment for all types of mental illnesses. It acts mainly on flexibility, improving mood and coping with stress (Rao et al., 2021). Evidence also suggests that yoga is effective during acute phases of schizophrenia in terms of compliance with treatment and reduction of anxiety and agitation. This may be attributed to potential effects on neural reconnection through meditation and concentration on the breath (Arasappa et al., 2021; Schulze et al., 2021).

Our review findings also suggested different effects of various forms of physical activity. For instance, physical exercises such as stretching, jogging and weight training are effective on positive symptoms and general well-being, while dance therapy positively affects negative symptoms. A plausible explanation underlying the effect of aerobic physical activity might be attributed to the increase in the hippocampus size compared to control groups (Girdler et al., 2019). This stems from the role of the hippocampus in memory, cognition, and executive functions (negative schizophrenia symptoms) (Girdler et al., 2019).

Physical exercise (jogging and strengthening) and zinc supplemen- tation are beneficial to the positive symptoms that quality of life Measured by the abbreviated WHO quality of life questionnaire (WHOQOL-BRE). In addition, physical activity is also effective in improving the quality of life of patients with schizophrenia by improving their physical condition and reducing their risk of chronic diseases.

4.1. Strengths and limitations

To our knowledge, our review is the first umbrella review that syn- thesizes and summarizes existing evidence on the effects of physical activity and nutrient supplementation in improving positive and nega- tive symptoms, cognitive impairment, and the quality of life of patients living with schizophrenia.

Therefore, our review has some limitations such as the non- integration of another type of systematic reviews of cross over trials, cohort, and case control studies. This was related to the trade-off be- tween comprehensiveness and feasibility of the review.

The majority of included systematic reviews were of low to moderate quality with the exception of Firth et al. (2017a) and Kim et al. (2023). However, our umbrella review has summarized the “gold standard” evidence on the effectiveness of physical activity and nutrient supple- mentation interventions on schizophrenia and in public health in gen- eral (Hariton and Locascio, 2018; Higgins et al., 2019) by focusing exclusively on systematic reviews of RCTs.

The heterogeneity and the use of different measurement scales of schizophrenia symptoms and well-being prevented us from assessing the cumulative effect of different interventions using meta-analysis. This is a common limitation in many umbrella reviews (Aromataris et al., 2015;

Higgins et al., 2019; Worswick et al., 2013). Only two systematic reviews included in this umbrella review have

reported effects on cognitive outcomes (Broderick et al., 2015; Firth et al., 2017a). As stated by Broderick et al. (2015) and Gebreegziabhere et al. (2022), most RCTs of physical activity interventions in patients with schizophrenia often underreport cognitive dysfunction symptoms. Finally, our umbrella review only focused on systematic reviews of RCTs, thus, recent well designed RCTs not yet included in a systematic review, may have been missed. For instance, an example is the recent RCT addressing the role of yoga in improving social cognition in schizophrenia not yet included in a systematic review (Govindaraj et al., 2021).

4.2. Implications for practice

Our umbrella review has summarized existing evidence about the importance of integrating physical activity and supplementation of micronutrients in patients with schizophrenia. Our results might inform national mental health programs, as an adjunct strategy, to foster the reduction of negative and positive symptoms and cognitive dysfunc- tions. This might improve the well-being of patients living with schizophrenia. Our review, in line with Gebreegziabhere et al. (2022), suggests the importance of promoting the assessment of cognitive symptoms in patients with schizophrenia and promotion of physical activity such as aerobic and yoga by skilled professionals to ease the suffering of patients living with schizophrenia.

We urge frontline workers including psychiatrists, psychologists, rehabilitators, and nutritionists to work collaboratively in multidisci- plinary teams to promote physical activity and nutrient supplementation while providing counseling about the appropriate physical exercise and nutrient supplementation to improve the well-being of patients with schizophrenia.

4.3. Implications for research

More attention should be paid to the standardization of measurement scales of positive, negative, cognitive, and quality of life scales in schizophrenia related future studies. Researchers also need to integrate physical activity into national health policies. More research is needed to understand the barriers preventing patients with schizophrenia from benefiting from nutrient supplementation and engaging in physical ac- tivity. Research is also needed to assess whether healthcare organiza- tions and urban environments are enabling environments for physical activity for patients living with schizophrenia at national and regional level and in urban and rural areas.

5. Conclusion

Our umbrella review provides a comprehensive summary of existing evidence in one single document about the effect of physical activity and supplementation of micronutrients to ease the suffering of those with schizophrenia. We, therefore, urge healthcare policymakers to take into consideration the integration of promoting physical activity and nutrient supplementations in National health policies aiming at improving the well-being of citizens including patients with schizophrenia.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Houda El Kirat: PhD candidate, conceptualization, screening, data extraction, formal analysis Writing- Original draft preparation,

H. El Kirat et al.

Schizophrenia Research 262 (2023) 112–120

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Visualization. Professor Zakaria Belrhiti, PhD supervisor, conceptualization,

building search strategies, title and abstract screening, methodological support, critical revisions of different drafts and supervision.

Professor Mohammed Khalis revised an earlier version of the manuscript with expertise in nutrition.

Professor Asmaa Khattabi, PhD supervisor, revised an earlier version of the manuscript and provided expertise in epidemiology.

Declaration of competing interest

We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

We bring to your attention, that this manuscript has not been sub- mitted for publication in any other journal.

Acknowledgement

NA.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.schres.2023.10.021.

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