Effectiveness of aerobic exercise in psychiatric disorders: Naturopathy has its say

Abstract

Aerobic exercise has long been known to improve cardiovascular, metabolic and mental health. While aerobic exercise has been used more frequently in teenagers and young adults to improve cognitive and psychiatric symptoms, recent evidence suggests that it is also effective in older patients. In this regard, clinical trial studies have observed that moderate-intensity aerobic exercise intervention significantly improved clinical, social, and cognitive symptoms of older people with schizophrenia. Working memory, verbal/visual learning, processing speed, and executive function were all improved, while social disability and positive and negative syndrome scale total, positive, negative, and general symptom scores were significantly reduced. Aerobic exercise was found to be an independent predictor of better psychosocial rehabilitation outcomes after controlling for important confounders. Exercise duration showed a linear correlation with improvement in social and cognitive functioning. Aerobic exercise has also been shown to improve cognition and reduce depressive symptoms in adolescents and young and older people with depression. Mechanistically, aerobic exercise has been shown to enhance neurogenesis, synaptic plasticity, and brain volume in association with improved cognition in laboratory animals. In conclusion, early intervention with moderate-intensity aerobic exercise may correct aberrant signaling pathways that lead to the development of cognitive and psychiatric symptoms in psychiatric disorders.

Key Words: Aerobic exercise; Psychiatric disorders; Cognitive symptoms; Psychiatric symptoms; Oxidative stress; Inflammation

Core Tip: Aerobic exercise has been shown to improve various domains of cognition, including processing speed, working memory, verbal/visual learning, and executive function. In addition, it has also been shown to effectively reduce psychiatric symptoms, social cognition, and disability in patients with psychiatric disorders (PD). These convincing outcomes of aerobic exercise could be due to its potential regulatory effect on glucose metabolism and improved mitochondrial function, reduced oxidative stress and inflammation. Therefore, aerobic exercise could be integrated as an essential step in the management of PD.

INTRODUCTION

Although there has been substantial progress in understanding the pathophysiology of psychiatric disorders (PDs), therapeutic advances have not proven particularly convincing[1-6]. While acute treatment with first-line medications can alleviate the classical symptoms in patients with PD, long-term treatment has been demonstrated to cause or worsen a number of pre-existing metabolic abnormalities, including adiposity/obesity, insulin resistance/diabetes, non-alcoholic fatty liver disease (NAFLD), and increase cardiovascular related mortality[3-7]. Since elevated oxidative stress and inflammation in PDs may trigger the development of these metabolic abnormalities[8-11], a number of clinical trials have been carried out using antioxidants and anti-inflammatory agents in combination with the first line of treatment for PDs[12-17]. However, just a few of these combinations have been demonstrated to have a somewhat greater effect than the placebo; the results are still inconclusive[16,17].

In recent years the use of aerobic exercise in PDs has attracted a lot of attention. Given that patients with PDs exhibit decreased tissue oxygenation (tissue hypoxia) at the time of diagnosis[18,19], this approach may prove to be successful. It has been demonstrated that hypoxia impairs metabolic and cognitive processes, increases oxidative stress and inflammation, while decreasing neurogenesis and synaptic plasticity, particularly under chronic condition[20,21]. Aerobic exercise may be a viable therapeutic alternative because these pathological landmarks have been well-established in patients with PDs[1-6,22]. As will be addressed later, the recent increase in the use of aerobic exercise in PDs is evidence of its efficacy.

In laboratory animals, aerobic exercise has been shown to increase synaptic plasticity, neurogenesis, and brain volume while also lowering oxidative stress, inflammation, and lipid abnormalities, along with improving cognition and classical symptoms in PDs[22-26]. Clinicians in psychiatry believe that enhancing cognition, including social cognition-is essential to helping patients integrate into their social and academic lives. Therefore, we discuss here the current evidence that supports the existence of hypoxia and how it relates to the cognitive and psychiatric symptoms of PDs as well as the outcomes of aerobic exercise intervention.

HYPOXIA IN PDS: ASSOCIATION WITH COGNITIVE AND PSYCHIATRIC SYMPTOMS

Recent data suggests that tissue hypoxia persists in adult patients with PDs, despite the fact that prenatal or neonatal hypoxia has been substantially associated with the risk of later developing psychiatric complications[18,19,27]. According to Huang et al[19], tissue hypoxia and acid retention were found in both acute and stable patients with schizophrenia, and they were strongly linked to glucose metabolism. In a similar vein, Hu et al[27] found that higher venous pH and depressive symptoms were linked to tissue hypoxia in patients with depression. These results imply that hypoxia may develop prior to the diagnosis/onset of classical symptoms in patients with PDs with or without genetic predisposition.

It has been demonstrated that hypoxia raises glucose levels by increasing gluconeogenesis; the extra glucose may then be converted into fatty acids and lipids through the de novo pathway[28]. As proposed in Figure 1, accumulation of fatty acids/Lipids synthesized via de novo pathway may be the primary mechanism linked to increased oxidative stress, inflammation, decreased neurogenesis, and synaptic dysfunction, but it may also be the primary source of metabolic abnormalities in PDs[6,11,28,29]. These pathological effects are thought to be the possible risk factors for cognitive and psychiatric symptoms in people with PDs[1,6,11,19,20]. Furthermore, the fact that hypoxia plays a crucial role in the development of diabetes, obesity, and NAFLD, which are extremely common in patients with PDs and become worse by antidepressant or antipsychotic treatment[6,11], provide evidence that hypoxia may appear on or before the onset of classical symptoms in patients with PDs. It has been demonstrated that aerobic exercise improves cognitive and behavioral symptoms while lowering these metabolic abnormalities.

Figure 1  Proposed effects of hypoxia in psychiatric disorders and amelioration by aerobic therapy.

AEROBIC EXERCISE IMPROVES COGNITION AND PSYCHIATRIC SYMPTOMS IN PDS

A number of studies have been performed in recent decades to evaluate the beneficial effects of aerobic exercise in laboratory animals, healthy adolescents, elderly people as well as in patients with psychiatric and neurological disorders[30-36]. In adolescents and young, mentally healthy people, aerobic exercise has been shown to improve various cognitive domains, including working memory, executive function, attention, cognitive flexibility, and inhibitory control[30,31]. Also, in older people, aerobic exercise regimen has shown more or less comparable cognitive improvements[32,33]. Using prospective and cross-sectional brain imaging data, Colcombe et al[34] demonstrated that aerobic exercise protected against age-related brain volume loss in older people, changes were seen in those brain regions, which are involved in the executive control processing and memory and are most vulnerable to the effects of aging.

In PDs, aerobic exercise interventions have produced promising results in reducing clinical symptoms in adolescent, adult as well as older patients with depression and schizophrenia. A network and dose response meta-analysis in children and adolescents revealed that resistance or aerobic exercise interventions were more beneficial than combined exercise in reducing depression, whereas mind-body activities had no considerable impact[35]. It was determined that the minimal effective dose was roughly 640 Metabolic Equivalent of Task (MET)-minute/week. Another dose response meta-analysis in children and adolescents reported that aerobic exercise dramatically reduced symptoms of depression in adolescents, especially in those with a diagnosis of depression[36]. The most effective exercise was moderate-intensity (4.0-5.9 METs), 30-45 minutes per session, three-four times per week, for six to ten weeks with an optimal dose of 590 METs-minute/week.

Additionally, a meta-analysis examined the results of aerobic exercise intervention in young adults (ages 17 to 31) and found that both short (less than 40 minutes) and long duration (more than 40 minutes) aerobic exercise significantly decreased symptoms of depression[37]. However, the ideal length of aerobic exercise varied based on the particular group and individual parameters examined, including age, health, and exercise tolerance. This study also found that young people with depression who engaged in 40 minutes of moderate-intensity aerobic exercise three times a week for six to eleven weeks experienced a more notable improvement in the symptoms of depression. Other randomized clinical trial studies reported that regular aerobic exercise increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor levels, which may have improved cognitive function and symptoms of depression in young adult (age 27-44 years) patients with depression[38]. The type, frequency, and intensity of aerobic exercise may have had an impact on the overall outcome. Similarly, several other meta-analyses reported that aerobic exercise dramatically improved executive and global cognitive function and decreased symptoms of depression in young adults and older individuals with depression with and without minor cognitive deficits[39-42].

In schizophrenia, aerobic exercise has shown promising results in lowering the risk of developing psychosis as well as reducing the symptoms of psychosis and cognition, and brain volume deficit[43-54]. According to a general population cohort study, physical exercise during childhood and adolescence was associated with a considerably lower incidence of psychosis[43]. Another study identified physical activity as being linked to a lower incidence of persistently distressing psychotic-like symptoms in those having polygenic risk for schizophrenia[44]. This suggests that even in people who have genetic predispositions, aerobic exercise may be useful in lowering the risk of psychosis.

Similar to adolescents and young mentally healthy people as discussed before, aerobic exercise has been demonstrated to enhance a number of cognitive domains, such as working memory, attention/vigilance, global cognition, and social cognition in young and older patients with schizophrenia[26,46-50]. According to some of these analyses, people with psychosis have also seen improvements in their cardiovascular health and quality of life[49,50]. A recent retrospective study by Ao et al[51] has provided real world evidence for aerobic exercise in elderly individuals with schizophrenia. According to the study, older inpatients with schizophrenia who participated in a moderate-intensity aerobic exercise program showed significant improvements in their cognitive, social, and clinical outcomes. In addition to a significant decrease in social disability and positive and negative syndrome scale (PANSS) total, positive, negative, and general scores, the study also demonstrated strong improvements in processing speed, working memory, verbal/visual learning, and executive function. The length of exercise was linearly correlated with improvements in social and cognitive functioning. After controlling for important variables, aerobic exercise was demonstrated to be an independent predictor of better psychosocial rehabilitation results using multivariate regression analysis.

LIMITATIONS AND RISKS OF AEROBIC EXERCISE, AND FUTURE DIRECTION

Aerobic exercise seems to have minimum risk of injury, especially, if used at moderate intensity and for short to medium duration. Evidence suggests that aerobic exercise is beneficial in alleviating symptoms of psychosis and depression, if initiated early. Its efficacy usually reduces from the age of 80, after that it usually has no significant effect on symptom reduction[39,40]. Although patients in most trial studies demonstrated strong adherence to aerobic exercise, lack of consistency regarding exercise types, dosage, and outcomes have been reported in some studies. The type of outcome is determined by the type of exercise and should be considered when integrating aerobic exercise programs in their treatment regime[40,47,50].

Although several adjunctive therapies/drugs have been used over the years in treating PDs, aerobic exercise appears to be safer and comparatively more effective. However, optimal type of aerobic exercise, its duration, and frequency have not yet been determined. Since patients with PDs, especially depression, display low physical activity levels, lack of drive related to negative and depressive symptoms, and a high prevalence of metabolic and cardiovascular complications; extensive clinical trials are required to study the effect of aerobic exercise on these measures[50,55]. Another important therapeutic aspect of aerobic exercise includes its effect on insomnia or sleep disorders characterized by poor sleep. Several meta-analyses have been conducted recently suggesting that aerobic exercise effectively reduced wake-up cycle, and symptoms of anxiety and depression in patients with insomnia[56-59]. Evidence suggests that insomnia is a serious comorbid condition or risk factor associated with various PDs with a prevalence of approximately 40%-50%; therefore, early intervention with aerobic exercise in patients with insomnia may delay or prevents the development of psychiatric complications[60,61].

CONCLUSION

PD are characterized by complex etiopathology, and recent data suggests that reduced tissue oxygenation (hypoxia) is another contributing factor. Although several therapeutic strategies, including a variety of combinations of synthetic and natural adjuvant substances with first-line medications, have been used in treating PDs, the outcome remains unconvincing. Aerobic adjunctive therapy, however, is showing promising success in treating PDs. Although aerobic exercise has long been known to have positive effects on metabolic, cardiovascular, and mental health, real-world evidence for its effectiveness in PDs has emerged only recently. In this context, physical activity during childhood and adolescence has been associated with better cognitive functioning and a lower risk of developing depression and psychosis in the general population. In adolescents and young adults with PDs, moderate-intensity aerobic exercise has been shown to significantly improve a number of cognitive domains, such as processing speed, working memory, verbal/visual learning, executive function, and attention, while reducing the symptoms of depression and psychosis. According to recent data, moderate-intensity aerobic exercise can also improve these cognitive domains in older patients with PDs while significantly reducing social impairment, PANSS total, positive and negative symptoms, as well as depressive symptoms. In experimental animals, aerobic exercise has been demonstrated to improve synaptic plasticity and neurogenesis while reducing oxidative stress, inflammation, and various metabolic abnormalities, including dyslipidemia, insulin resistance, and obesity, in addition to improving psychopathology and cognition. These pleiotropic outcomes imply that moderate-intensity aerobic exercise may be incorporated as an essential part of PD treatment, beginning in childhood or adolescence.

ACKNOWLEDGEMENTS

Facilities provided by the Department of Biotechnology, Era's Lucknow Medical College and Hospital, and Faculty of Science, Era University, Lucknow, India are gratefully acknowledged.