The Effect of Muscular Strength on Depression Symptoms in Adults: A Systematic Review and Meta-Analysis

The aim was to systematically review the relationship between muscular strength (MS) and depression symptoms (DS) among adults, and conduct a meta-analysis to determine the pooled odds ratio (OR) for the relationship between MS and DS. The strategies employed in this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies published up to December 2019 were systematically identified by searching in the PubMed, Scopus, and Web of Science electronic databases. Inclusion criteria were: (1) cross-sectional, longitudinal and intervention studies; (2) outcomes included depression or DS; (3) participants were adults and older adults; and (4) the articles were published in English, French, Portuguese, or Spanish. A total of 21 studies were included in the review, totalling 87,508 adults aged ≥18 years, from 26 countries. The systematic review findings suggest that MS has a positive effect on reducing DS. Meta-analysis findings indicate that MS is inversely and significantly related to DS 0.85 (95% CI: 0.80, 0.89). Interventions aiming to improve MS have the potential to promote mental health and prevent depression. Thus, public health professionals could use MS assessment and improvement as a strategy to promote mental health and prevent depression.


Introduction
Depression is a mental health disorder affecting more than 300 million adults around the world [1]. It is the largest contributor to worldwide disability, and leads to almost one million suicide deaths annually [1]. The most common treatment for depression includes pharmacotherapy and psychotherapy [2,3], which, in the long term, can be expensive and costly for health care systems due to the prevalence of the disorder [4]. In order to address the health problem of depression that affects

Data Sources and Searches
Studies published up to the 31st of December 2019 were systematically identified by searching in the PubMed, Scopus, and Web of Science electronic databases. The search was performed using the following combination of terms: Handgrip, Hand-Grip or "Hand Strength" or "Grip Strength" or "Muscular Strength" or "Muscular Fitness" or "Muscular Train*" and depression or depressive or "Mental Health" or anxiety or "Psychological Functioning". Retrieved titles and abstracts were assessed for eligibility for inclusion by two authors. Duplicate entries were removed. Relevant articles were retrieved for a full read. The same two authors reviewed the text of potential studies, and decisions to include or exclude studies in the review were made by consensus.

Study Selection
Articles published up to December 2019 were eligible for inclusion. Specific criteria were: (1) design criterion: cross-sectional, longitudinal and interventional studies; (2) outcome measure criterion: studies were included if the outcomes included depression; (3) participants: adults and older adults; (4) language criterion: articles published in English, French, Portuguese, or Spanish; and (5) exclusion criterion: articles were excluded if they did not meet inclusion criteria or did not include findings related to the inclusion criteria. Published conference proceedings, conference abstracts, and theses or studies including animals were also excluded. Finally, studies focusing on general mental health, anxiety, and mood were excluded because they preclude concluding the isolated effect of muscular strength on depression.

Data Extraction and Quality Assessment
The following information was extracted from each study: author's name and year of publication, study design, country, sample characteristics (number of participants, sex, age), the instrument for assessing the depression symptoms, the instrument for assessing muscular strength, main results, and study quality. For the intervention studies, the following were extracted: duration of intervention, description of the program, intensity, duration, and frequency. For longitudinal studies, the time of follow-up was also extracted. The methodological quality of the studies was assessed using the Quality Assessment Tool for Quantitative Studies. It is a 19-item checklist, assessing methodological domains: selection bias, study design, confounders, blinding, data-collection methods, withdrawals and dropouts, intervention integrity, and analyses. A global rating was determined based on the scores of each component. Two researchers rated the studies in each domain, as well as the overall quality of each study. Discrepancies were resolved by consensus.

Data Synthesis and Analysis
This review analysed the relationship between muscular strength and depression. The details for each study are presented consistently. Data from all studies were pooled using Review Manager 5.3. For the five clinical trial studies, the instruments used to assess the muscular strength or the depression symptoms were different among the studies. From the 16 observational studies, the data from 9 were used for meta-analysis [11,[21][22][23][24][25][26][27][28]. The seven studies not included were eliminated based on the heterogeneity of the association measure between muscular strength and depression symptoms. Two reported the comparison between the effect of high vs. low muscular strength on depression [29,30]; two reported the muscular strength difference between depressed vs. not depressed cases, and the other three reported results stratified by weight status or quartiles of muscular strength [31]. The homogeneity of the odds ratio of the studies included in the meta-analysis was assessed using I 2 statistics. Values of ≥50% were considered substantial heterogeneity [32]. As there was significant heterogeneity, a random effects model was used to calculate the pooled odds ratio. Sensitivity analyses were carried out by successively omitting one study at each turn. A Forest plot was performed to showcase each included study log-odds, odds ratio (95% confidence interval (CI)), standard error and weight as lines, and the pooled odds ratio from all studies as a diamond.

Literature Search
The primary search in the databases yielded 782 citations. After excluding the duplicates (n = 359), the title and abstract of 423 articles were screened. Of these, 378 citations were discarded after reviewing the title and the abstract because it was clear that they did not contain an assessment of muscular strength and depression symptoms. After having read the full text of the remaining 45 citations, 24 were discarded, either because they did not have depression symptoms as the outcome variable (n = 15), were not focused on muscular strength (n = 4), were not empirical studies (n = 3), or were written in a language other than English, French, Portuguese, or Spanish (n = 2). The flow diagram is presented in Figure 1.
Health Questionnaire, and the Beck Depression Inventory were the most used scales to assess the depression symptoms (each scale in four studies). The other scales used were the Center for Epidemiologic Studies Depression Scale, EuroQol Five-Dimension Questionnaire, Hamilton Depression Rating Scale Hopkins' Symptom Checklist, Mental Health Inventory, and Psychosis Evaluation Tool for Common Use by Caregivers. Seven studies were considered to be of weak methodological quality, seven of moderate quality, and the other seven of strong quality.

Principal Findings
The description of the studies reporting the relationship between muscular strength and depression symptoms is presented in Table 1. The results from two clinical trials [33,34] and one observational study [13] were inconsistent. A relationship between muscular strength and depressive symptoms was not observed. However, in one study, the neurotransmitter factors, such as serotonin, dopamine, epinephrine, and norepinephrine significantly decreased in the strength exercise group but not for the control group [33]. From the other clinical trial studies, the muscular strength decreased the depression symptomatology [35][36][37]. Results demonstrated significant differences in all indicators of depression after completing 12 weeks of training [35], that low muscle strength increased depression symptomatology in patients with fibromyalgia [37], and that strength training intervention significantly decreased depressive symptoms [36]. The other observational studies showed that independently of sex, age, and country, depression symptoms were significantly associated with a reduced handgrip strength [11,21,22,24,[27][28][29][30][38][39][40]. Furthermore, adults in the lower tertile or quartile for muscle strength had a significantly higher risk for depressive symptoms compared with those in the third tertile or fourth quartile [23,25,26,31].  Table 1 presents the studies' characteristics. A total of 21 studies were included in the review, totalling 87,508 adults aged ≥18 years, from 26 countries. Most studies were cross-sectional (n = 12), five were clinical trials, and four were prospective studies. Five studies were performed in South Korea, two in Brazil, two in Spain, two in the United States, and the others were performed in Australia, Belgium, China, Denmark, Finland, Ireland, Japan, Turkey, and the United Kingdom. One study was performed in six countries (China, Ghana, India, Mexico, Russia, South Africa). The Geriatric Depression Scale, Patient Health Questionnaire, and the Beck Depression Inventory were the most used scales to assess the depression symptoms (each scale in four studies). The other scales used were the Center for Epidemiologic Studies Depression Scale, EuroQol Five-Dimension Questionnaire, Hamilton Depression Rating Scale Hopkins' Symptom Checklist, Mental Health Inventory, and Psychosis Evaluation Tool for Common Use by Caregivers. Seven studies were considered to be of weak methodological quality, seven of moderate quality, and the other seven of strong quality.

Principal Findings
The description of the studies reporting the relationship between muscular strength and depression symptoms is presented in Table 1. The results from two clinical trials [33,34] and one observational study [13] were inconsistent. A relationship between muscular strength and depressive symptoms was not observed. However, in one study, the neurotransmitter factors, such as serotonin, dopamine, epinephrine, and norepinephrine significantly decreased in the strength exercise group but not for the control group [33]. From the other clinical trial studies, the muscular strength decreased the depression symptomatology [35][36][37]. Results demonstrated significant differences in all indicators of depression after completing 12 weeks of training [35], that low muscle strength increased depression symptomatology in patients with fibromyalgia [37], and that strength training intervention significantly decreased depressive symptoms [36]. The other observational studies showed that independently of sex, age, and country, depression symptoms were significantly associated with a reduced handgrip strength [11,21,22,24,[27][28][29][30][38][39][40]. Furthermore, adults in the lower tertile or quartile for muscle strength had a significantly higher risk for depressive symptoms compared with those in the third tertile or fourth quartile [23,25,26,31]. Figure 2 shows the forest plot of the odds ratio and 95% CI of each study and the odds ratio of the random effects model. A moderate heterogeneity among studies was detected (I 2 =55%; χ 2 = 17.96, df = 8; p = 0.02). Based on nine observational studies [11,[21][22][23][24][25][26][27][28], including 62,831 cases, the presence of depression symptoms was negatively associated with muscular strength. The pooled odds ratio from the random-effects model was 0.85 (95% CI: 0.80, 0.89).  Figure 2 shows the forest plot of the odds ratio and 95% CI of each study and the odds ratio of the random effects model. A moderate heterogeneity among studies was detected (I 2 =55%; χ 2 = 17.96, df = 8; p = 0.02). Based on nine observational studies [11,[21][22][23][24][25][26][27][28], including 62,831 cases, the presence of depression symptoms was negatively associated with muscular strength. The pooled odds ratio from the random-effects model was 0.85 (95% CI: 0.80, 0.89).

Discussion
This study sought to review the relationship between muscular strength and depressive symptoms in adults and older adults. Findings suggest that increased muscular fitness may have a beneficial effect on depression symptoms. Furthermore, the meta-analysis findings indicate that muscular fitness is inversely and significantly related to depression symptoms among adults and older adults. This is of importance because depression is the greatest non-communicable disease contributing to the loss of health [1] and it is associated with comorbidity [41], a higher risk of suicide [42], and premature mortality [43].
Muscular strength is recognized as an important health indicator, mainly because it is associated with a lower risk of mortality in the adult and older adults population, regardless of age [8]. Moreover, it is independently associated with cardiometabolic risk and metabolic syndrome in adults and older adults [44,45]. Specifically among older adults, muscular fitness is associated with sarcopenia [46], functional limitations and disabilities [47]. Thus, it is considered a useful marker of frailty in the older adult population [48]. In this systematic review and meta-analysis, muscular fitness was also found to be inversely associated with depressive symptoms. Several mechanisms may explain the observed inverse association between muscular strength and depression symptoms. One possible mechanism is the relationship between muscular strength and sarcopenia [46], functional limitations and disabilities [47]. The relation between muscular strength and these health outcomes may transfer to depression by increased disability, as people with lower muscular strength are less independent and have more

Discussion
This study sought to review the relationship between muscular strength and depressive symptoms in adults and older adults. Findings suggest that increased muscular fitness may have a beneficial effect on depression symptoms. Furthermore, the meta-analysis findings indicate that muscular fitness is inversely and significantly related to depression symptoms among adults and older adults. This is of importance because depression is the greatest non-communicable disease contributing to the loss of health [1] and it is associated with comorbidity [41], a higher risk of suicide [42], and premature mortality [43].
Muscular strength is recognized as an important health indicator, mainly because it is associated with a lower risk of mortality in the adult and older adults population, regardless of age [8]. Moreover, it is independently associated with cardiometabolic risk and metabolic syndrome in adults and older adults [44,45]. Specifically among older adults, muscular fitness is associated with sarcopenia [46], functional limitations and disabilities [47]. Thus, it is considered a useful marker of frailty in the older adult population [48]. In this systematic review and meta-analysis, muscular fitness was also found to be inversely associated with depressive symptoms. Several mechanisms may explain the observed inverse association between muscular strength and depression symptoms. One possible mechanism is the relationship between muscular strength and sarcopenia [46], functional limitations and disabilities [47]. The relation between muscular strength and these health outcomes may transfer to depression by increased disability, as people with lower muscular strength are less independent and have more difficulties performing activities of daily living [49], which is linked to depression symptoms [50,51]. Moreover, muscular strength is also associated with frailty and health-related quality of life [52]. Another possible explanation is the release of cytokines and myokines into the circulatory systems in response to muscle contraction. It is suggested that myokines might protect against the risk of depression [53]. Furthermore, older adults' inflammatory profile is associated with frailty and sarcopenia, which can increase the risk of depression [54][55][56].
When examining the association between muscular strength and depression, one must consider the potential mediating role of physical activity. Physical activity, most notably muscle-strengthening activity, is known to be the most important modifiable factor related to muscular strength; therefore, higher muscular strength levels are likely to be related to greater physical activity levels [17]. Furthermore, muscular strength and physical activity share most of the mechanisms through which they may affect depression symptoms. Nevertheless, physical fitness mirrors both participation in physical activity and the state of physiological systems, being suggested that because of that the relationship between physical fitness and health outcomes may be stronger than the relationship between physical activity and those same health outcomes [57]. Moreover, changes in fitness due to participation in physical activity are not immediate and may take weeks to be measurable. Some of the studies included in this review controlled the analysis for physical activity participation and still concluded that muscular strength was associated with depression, independently of physical activity [21,[23][24][25]27]. The mediating role of physical activity in the relationship between muscular strength and depression symptoms has not been explored yet, and thus, future research should investigate how much of this relationship is mediated by physical activity.
Depression has one of the greatest disease burdens in several countries worldwide [42]. It is usually treated using pharmacotherapy and psychotherapy [2,3], but both treatment options are expensive and increase the health costs for health care systems [4]. To address this public health problem and possibly reduce the present and future burden of the disease, different strategies are needed. The association between the muscular strength and depression symptoms observed in this review indicates that promoting muscular fitness through physical activity and exercise might be used as a potential strategy to fight depression. Furthermore, a recent systematic review and meta-analysis revealed that resistance training had a moderately positive effect on disability and function in older adults with or at risk of disability [58]. This is important because disability and function are related to depression. Moreover, measures of muscular strength, such as handgrip, could be used as one of several indicators of depression, or for the development of depression symptoms, and its assessment could be promoted in the primary health care systems, as it is already suggested to be for mortality [8]. The early detection and prevention of depression symptoms, and mental health promotion in the health care systems, may lead to healthier populations and reduced health care costs. Moreover, improving muscular fitness would not only promote mental health but also promote cardiometabolic health and the quality of life [45,52,58].
To our knowledge, this is the first systematic review to investigate associations, between muscular fitness and depression symptoms in adults and older adults, using a meta-analysis to determine the pooled odds ratio for the relationship between muscular strength and depression symptoms. Nevertheless, these systematic review and meta-analysis findings should be taken in light of some limitations that must be acknowledged. Most studies used handgrip strength as a measure of muscular strength, while other studies used different measures. This leads to heterogeneity in the muscular strength outcome. Even though the studies were assessed according to their methodological quality, they were not weighed or ranked according to it for the systematic review. Thus, the findings from studies with weaker quality and smaller sample sizes were given no less importance than the findings from studies with strong research designs and larger sample sizes. Furthermore, most included studies were cross-sectional and therefore associations of the temporal direction cannot be certainly assessed. Search terms were selected to identify articles that associate muscular strength and depression. Nonetheless, some articles were eventually left out, because in the title or abstract, they did not have a term that could be associated with muscular strength or depression.

Conclusions
Muscular strength is inversely and significantly related to depression symptoms among adults and older adults. This may be partially explained by physical activity, but also by the associations between muscular fitness and functional limitations and disabilities, as well as frailty and health-related quality of life, which in turn are related to depression symptoms. Interventions aiming to improve muscular fitness have the potential to promote mental health and prevent depression. Thus, public health professionals could use muscular strength assessment and improvement as a strategy to promote mental health and prevent depression. These findings are of the utmost importance for public policies where the strength of the connection between physical and mental factors, in the promotion of mental health and well-being, is not always duly considered.