Physical activity, exercise, and mental disorders: it is time to move on

Abstract Introduction Physical activity, conceptualized as any bodily movement that results in energy expenditure, and its structured form, exercise, play an important role in public health, preventing and treating a wide range of physical conditions, including metabolic and cardiovascular diseases and obesity. Objective This article aims to provide a brief overview and summary of the evidence on: 1) the preventive effects of physical activity on a wide range of mental disorders; 2) the role of physical activity in promoting the physical health of people with mental disorders; 3) the role of exercise as a strategy to manage mental health symptoms in a range of mental disorders; and 4) the challenges and barriers faced when implementing exercise in clinical practice. Methods This was a narrative review. Results Compelling evidence has demonstrated that physical activity and exercise can also prevent common mental disorders, such as depression and anxiety disorders, and have multiple beneficial effects on the physical and mental health of people with a wide range of mental disorders. This body of evidence has been incorporated in national and international guidelines over the last decades, which have recommended the inclusion of physical activity and exercise as therapeutic approaches for mental disorders, mainly for depression and schizophrenia. Nonetheless, implementation into clinical practice has been slow, probably due to barriers associated both with patients and mental health professionals. Conclusion Increases in physical activity levels in populations are likely to reduce the mental health burden. Exercise interventions should be incorporated to the routine care of people with mental disorders due its multiple benefits on physical and mental health outcomes. A multidisciplinary approach is needed to overcome patients barriers and enhance adherence and benefits.


Introduction
Mental disorders are highly prevalent and burdensome. It is estimated that approximately 12% of the global population suffered from a mental disorder in 2019, accounting for roughly 5% of the disabilityadjusted life years (DALYs) and 16% of the years lived with disability worldwide. 1 The mental health burden is further compounded by a high prevalence of comorbid somatic disorders, [2][3][4] leading to a life expectancy 15 to 20 years shorter when compared to that of the general population. 5 Risk factors associated with this high rate of physical comorbidities are a genetic vulnerability in people with mental disorders, side effects of pharmacological treatments, and a poor lifestyle, including unhealthy eating habits, substance abuse, poor sleep, low levels of physical activity, and long periods spent on sedentary behavior. [6][7][8][9] Expenses in mental health care, led by expenses in pharmacological interventions, have increased substantially over the last decades. 10 However, current approaches have not been sufficient to further reduce the prevalence of these disorders at a population level -in fact, that prevalence has remained almost stable over the last 30 years worldwide. In fact, rates of common mental disorders such as depression and anxiety appear to even be increasing among the younger generations. 7 Pharmacological treatments, including antidepressants 11 and antipsychotics, 12 are still the frontline strategy for symptom management. However, the long-term treatment effects of pharmacotherapy are being questioned. 13 For many people with mental disorders, psychotropic medication does not result in clinically meaningful improvement in the long-term, and side effects such as significant weight gain, 12 elevated blood glucose levels, and loss of sexual interest, among others, 14 are considerable. 15,16 These side effects often result in medication discontinuation and distress and can negatively impact patients' lives. [17][18][19] There has also been little improvement in the primary prevention of mental disorders, with clear gaps in both the evidence and implementation of such interventions. 6 Thus, additional approaches towards the prevention and treatment of mental disorders, which can be delivered alongside or in the absence of traditional mental health care strategies, are needed to reduce the global and growing burden of these conditions. A large and new body of evidence has been accumulated over the last decades suggesting that physical activity and exercise might be such approaches. Although the body of evidence can be considered new, these interventions are not.
"Walking is man's best medicine," quoted Hippocrates (460-377 B.C.). 20 The quote demonstrates that physical activity, nowadays defined as "any bodily movement produced by skeletal muscles that results in energy expenditure," 21 and exercise, defined as "a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness," 21 have been recognized, since the ancient Greeks of the classical period, as having preventative and therapeutic effects on human health. Currently, a plethora of evidence supports the claim that "exercise is medicine," 22 due to its preventative and therapeutic effects on a broad range of physical conditions, including neurological, metabolic, cardiovascular, and pulmonary diseases, musculoskeletal disorders, and cancer. 23 A Evidence was also found for the protective effects of physical activity against incident stress and anxiety. 32 A meta-analysis of 11 prospective studies, including There is limited and conflicting evidence on the protective effects of physical activity against bipolar disorders and schizophrenia. For bipolar disorder, one prospective study found that higher levels of physical activity were associated with a greater likelihood of incident bipolar disorder at follow-up. 33 However, a Mendelian randomization study found that physical activity has a causal protective effect against bipolar disorders (OR = 0.49, 95%CI = 0.31-0.76). 34 It is expected that additional studies will offer new insights into the topic.
Lastly, evidence from a meta-analysis of 5 prospective studies demonstrated that higher physical activity levels were associated with a lower risk of incident psychosis or schizophrenia (OR = 0.72, 95%CI = 0.53-0.99). 35 However, when the analysis was limited to the two studies that adjusted for confounding factors, the significant associations were no longer supported. 35 The Mendelian randomization study that addressed the topic does not support the notion that physical activity protects from psychosis or schizophrenia. 34

Effects of physical activity and exercise on the physical health of people with mental disorders
Physical activity is a well-established protective factor against diabetes, metabolic syndrome, cardiovascular diseases, 23 and all-cause mortality in the general population. 36  = -0.98), followed by psychoeducation (SMD = -0.77), in people with schizophrenia. 40 Changes in lipid profile, markers associated with incident cardiovascular diseases, and cardiovascular mortality are also evident. 41 In people with depression, exercise significantly increases high-density lipoproteins levels. 38  Meta-analytical evidence demonstrates that exercise effectively reduces depressive symptoms in people with depression (people with subclinical symptoms or with a diagnosis of major depressive disorder). 52 In people with major depression, the effect size was large (SMD = 1.13, 95%CI = 0.46-1.81) when compared to physically inactive control groups. 52 In another meta-analysis, aerobic and mixed (aerobic and strength combined) exercises seemed to be more effective than strength exercises alone. 53  There is some evidence from nonrandomized studies that exercise might effectively reduce depressive symptoms in people with bipolar disorders, but there is a paucity of studies reporting the effects of exercise on manic or hypomanic symptoms. 59 In fact, some people with bipolar disorders refer to exercise as a "double-edged sword," as it has the potential to be both beneficial and harmful at the same time, provoking relaxation and a lift in mood. 60 Since these findings are based on qualitative studies, well-designed trials are required to clarify these effects in more detail.

Conclusions
The current evidence demonstrates that physical activity increments at a population level is likely to reduce the prevalence of mental disorders, particularly common mental disorders (depression and anxiety).