Resistance Exercise for Anxiety & Depression: Efficacy & Plausible Mechanisms

Abstract

Anxiety and depressive symptoms and disorders are prevalent and poorly treated. The salutary benefits of resistance exercise training, a potential alternative therapy, are well-established, but mental health effects are understudied. This review summarizes the most rigorous evidence regarding efficacy of resistance exercise and provides a primer for putative psychobiological mechanisms.

Resistance Exercise for Mental Health: A Primer

Anxiety and depressive symptoms and disorders are prevalent and debilitating public health burdens for which successful treatment is limited (https://www.nimh.nih.gov/health/statistics/any-mood-disorder). The salutary benefits of resistance exercise, or muscle-strengthening exercise involving exerting force against a load (Box 1), are well-established. However, the anxiolytic and antidepressant effects of resistance exercise have remained understudied compared to aerobic activity; importantly, the psychobiological mechanisms, which further elucidate how and why resistance exercise training (RET) improves mental health, are poorly understood. Thus, this brief review synthesizes the most rigorous evidence of the efficacy of RET for anxiety and depression and serves as a primer for the putative mechanisms which may contribute to, and potentially underlie, these effects.

Text Box 1. Resistance Exercise Training (RET) Conceptualization, Guidelines & Descriptive Epidemiology.

Aerobic exercise, or planned, repetitive, and purposeful skeletal muscle actions through activities like walking, running, and cycling, is likely more familiar to the general public and more well-studied in the physical and mental health literature. Muscle strengthening exercise, sometimes referred to as strength/weight/resistance training or exercise, is a voluntary activity that includes the use of weight machines, exercise bands, hand-held weights, or one’s own body weight to exert force against a load. Acute resistance exercise refers to a single bout/session of resistance exercise, and RET refers to the regular accumulation of resistance exercise bouts/sessions to generate a training response to enhance or maintain muscular fitness, physical, and/or mental health. Current guidelines recommend completion of at least eight resistance exercises targeting the major muscle groups, performing at least two sets of eight to 12 repetitions each with proper form, at least two days per week, progressing the intensity (i.e., resistance/weight) across time. The available large-scale epidemiological studies indicate that adults generally report engaging in little, if any, muscle strengthening exercise, with very few meeting the recommended two sessions per week [12]. Therefore, there is substantial opportunity to increase RET participation.

Effects of RET on Anxiety Symptoms & Disorders

Evidence, particularly from gold standard randomized controlled trials (RCTs), support the anxiety-reducing effects of exercise training among otherwise healthy adults, adults with chronic conditions, and Panic Disorder and Generalized Anxiety Disorder (GAD) [1]; however, this work has largely focused on aerobic exercise. Meta-analyses of the most rigorous evidence from RCTs that aggregate effects into a digestible overall expected mean effect size have shown that RET results in small-to-moderate improvements in anxiety symptoms among both healthy and chronically-ill adults [2]. RET for subclinical or clinical anxiety disorders is critically understudied. The only rigorously designed RCT of RET among adults with a clinical anxiety disorder showed that six-weeks of twice-weekly lower-body RET elicited clinically meaningful reductions in the severity of Generalized Anxiety Disorder (GAD) (i.e., six of 10 RET participants no longer met criteria for GAD following intervention) and moderate-to-large improvements in associated signs and symptoms [3]. However, this and other available trials have been limited by small sample sizes, generally inconsistent reporting of important trial characteristics, including adherence, compliance, and medication use, poor reporting of features of the RET stimulus, particularly intensity, session duration and overall RET dose, and poor ecological validity (i.e., RET that someone could/would engage in outside a study setting).

Effects of RET on Depressive Symptoms & Major Depressive Disorder

Exercise effects on depression are comparatively more well-studied than anxiety, primarily owing to a misconception that exercise may act as a stressor to elicit anxiety. Evidence from quantitative syntheses support the depression reducing, or antidepressant, effects of aerobic exercise training among otherwise healthy adults, adults with a chronic condition, and among depressed patients [4], but less is known about RET for depressive symptoms and disorders. A formative quantitative review found that RET elicited significant and clinically-meaningful (i.e., >50% reduction in severity from baseline, comparable to antidepressant medication and behavioural therapies) reductions in depressive symptoms among healthy and chronically-ill adults [5]. Importantly, near one-standard-deviation, large improvements were found among clinically depressed adults [5], and, aerobic exercise training and RET resulted in similar improvements when compared directly in the same participant samples. Similar to the evidence for anxiety, these findings should be interpreted in the context of limitations of the available trials, including variable, and often small, samples, poor reporting of intervention characteristics, especially features of the RET and overall dose, a predominant focus on self-reported severity, a lack of direct comparisons with other established therapies, and poor ecological validity for RET. To this end, recent RCT evidence, though from a small sample who were not clinically depressed, showed that ecologically-valid, guidelines-based RET elicited large depressive symptom reductions among young adults with and without subclinical GAD, for which depressive symptoms are highly comorbid and worsen severity [6].

Future Implications

Though the available evidence from largely small samples of variable quality supports that RET improves anxiety and depressive symptoms and disorders (though disorders are scarcely studied), there is a critical need for confirmatory, definitive RCTs that adequately address limitations regarding ecological validity, minimal dose thresholds for benefits, and the comparative effectiveness of RET to established frontline therapies. Moreover, even less is known regarding putative mechanisms of action for RET in both anxiety and depression. The following section addresses some of the most provocative target mechanisms, particularly overlapping mechanisms, for RET effects on anxiety and depression.

Plausible Psychobiological Mechanisms of RET’s Mood Effects

As originally detailed in a seminal review [7], several plausible psychobiological mechanisms have been hypothesized for RET’s anxiolytic and antidepressant effects. These are consistent with those generally posited for aerobic exercise, including effects on monoamine neurotransmitters and pathways, interactions of immune and serotonergic pathways, neurotrophic factors, neuroanatomical structure and function, and neurovisceral integration, or heart-brain crosstalk (Box 2).

Text Box 2. Neurobiological/Psychobiological Mechanisms of Exercise Training.

A seminal review of the neurobiology of exercise [7] highlighted several mechanistic pathways by which exercise training may improve brain health, and, subsequently mental health. In the context of biological plausibility, to support exercise training as a viable therapeutic, what is known regarding the neurobiological consequences of exercise must align with what is known about the etiology of mental illness, though a lack of consistent underlying pathological neurobiological abnormalities in mental illness hinders this effort. Nevertheless, exercise training clearly influences brain plasticity, facilitating neurogenesis, neuroadaptation, and neuroprotection, plausibly through effects on neurotrophic factors like brain-derived neurotrophic factor and insulin-like growth factor. Exercise training also attenuates neural responses to stress in brain regions/pathways that regulate peripheral sympathetic activity (supporting ‘heart-brain cross-talk). Thus, exercise training can mitigate central and peripheral sympathetic activity and selectively modulate norepinephrine, and other neurochemicals, plausibly mitigating mental health consequences of cardiometabolic insults, oxidative stress, and immunosuppression. Moreover, exercise training provides protection against ischemic, traumatic, and toxic brain insults through its neuroprotective effects. Multiple mechanisms involving complex integrated responses from multiple metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and brain regions support ways that exercise may influence the central nervous system and mental health [7].

Potential RET-specific mechanisms also include increases in insulin-like growth factor 1 (IGF-1). For example, animal models have shown increased hippocampal IGF-1, which may be a marker of neuroplasticity and involved in mood enhancement, in rats following RET [8]. Another provocative mechanistic target is abnormal cerebral blood flow, which has been hypothesized to underlie poor mental health (e.g., the “vascular depression” hypothesis). The few RET trials that have investigated this mechanism suggest RET may improve global blood flow, improve blood flow in specific regions, and decrease cerebral pulsatility, a measure of the discontinuity of blood flow [9]. A third emerging potential mechanism involves the benefits of controlled breathing that is inherent to proper RET technique to ensure adequate muscle oxygenation (i.e., inspiration during eccentric contraction, exhalation during concentric contraction). A recent meta-analysis showed deliberately controlled breathing resulted in small-to-moderate improvements in self-reported stress, anxiety symptoms, and depressive symptoms [10]. Mechanisms underlying the effects of controlled breathing are likely complex. Effects may be achieved through temporal coherence of respiratory, blood pressure, and cardiac oscillations which improve vagally-mediated heart rate variability to produce a cascade of neural activation that plausibly contributes to mental health benefits [11].

As symptoms of depression and anxiety have considerable overlap and high comorbidity, the hypothesized mechanisms of action of RET are likely, to some degree, shared in achieving RET’s antidepressant and anxiolytic effects. Were a specific mechanism identified that only mediates the antidepressant or anxiolytic benefits of exercise, much could be learned about the pathophysiology of depression and/or anxiety, as well as the neurobiology of exercise. As a whole, animal modelling has largely informed hypothesized mechanistic targets, with limited data in humans, particularly with clinical conditions; thus, focused studies of human-subjects that concurrently consider peripheral (i.e., blood-based, heart-rate variability, skeletal muscle gene expression) and central (i.e., brain-based, oxygenation, functional connectivity in frontal and limbic regions) mechanisms are clearly needed to specifically determine what or which mechanism(s) are predominantly involved in the anxiolytic and antidepressant responses to RET.

Concluding remarks

In sum, RET is shown to produce significant anxiolytic and antidepressant effects in healthy and in clinical populations (i.e., GAD and MDD, though from small-sample trials to date). There is substantial promise in evaluating the mechanisms underlying these effects of RET due to the ability for future interventions and practice to target these mechanisms to maximize their effects and potentially optimize prescription via precision medicine approaches. Recent improvements in animal modelling of resistance exercise will also allow for better mechanistic insights at the cellular and molecular level. Based on extant small-trial data, there is an urgent need for larger trials that evaluate the efficacy and effectiveness of RET for anxiety and depression with concurrent evaluations of the most promising mechanisms (IGF-1, cerebrovascular adaptation, and controlled breathing) to advance this field.