In a recent study published in the journal Translational Psychiatry,  researchers from University College London discussed the possible mechanisms through which depression impacts motivation and its association with inflammation. They also proposed a novel framework for understanding the pathways through which exercise increases interest and motivation and alleviates depressive symptoms.

Study: From movement to motivation: a proposed framework to understand the antidepressant effect of exercise. Image Credit: Dragana Gordic / Shutterstock

Interest-activity symptoms

Depression is a growing mental health concern and is associated with significant levels of disability across the world. Depressive symptoms, such as persistent low mood, fatigue, cognitive impairments, anhedonia, or a lack of interest or pleasure in the activities of life, are categorized as interest-activity symptoms. These symptoms contribute substantially to depression-associated disability by hindering work, social interactions, and life satisfaction.

The response to treatments such as selective serotonin reuptake inhibitors is also low in most patients, possibly due to the mechanistic heterogeneity of the disease. Interest activity symptoms are strongly associated with impaired motivation. Especially in patients with anhedonia, the lack of reward processing leads to a reluctance to exert effort. Given the role of dopamine in motivation and reward processing, dopaminergic agents have also been explored as treatment options, but their success has been limited.

However, aerobic exercise and other forms of physical activity, also known to improve dopamine transmission, are effective in reducing cognitive impairment, changing neuroendocrine responses, and lowering oxidative stress.

The mechanisms through which physical activity improves motivation and alleviates interest-activity symptoms remain unclear. Understanding these mechanisms could help provide more effective and individually tailored exercise programs to treat depression.

A Areas signalling reward (green), effort (red) and involved in cognitive control (blue), with areas involved in integrating reward and effort outlined in yellow. White text indicates known modulation by physical activity, especially aerobic exercise. Not all anatomical connections are depicted for reasons of clarity. Light shading (AI, VS, dlPFC) indicates that the region is situated more laterally than the slice depicted. B Cognitive processes corresponding to the neural changes illustrated in (A), and how different components implicated in effort-based decision making for reward are affected by exercise. aMCC anterior mid-cingulate cortex, dlPFC dorsolateral prefrontal cortex, vmPFC ventromedial prefrontal cortex, VS ventral striatum, AI anterior insula, IL-6 interleukin 6, IL-1β interleukin-1 beta, EEfRT effort-expenditure for rewards task, AGT apple gathering task.

Motivational dysfunction

Impaired reward processing is thought to drive the two major motivational symptoms of apathy and anhedonia, which are also associated with schizophrenia and neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. While apathy is characterized by a lack of motivation or interest in various activities, anhedonia is the absence of pleasure or joy in previously enjoyable activities.

Individuals with anhedonia and apathy show a lower sensitivity to rewards and poor reward-based learning. Computational models have been used to examine various reward processing parameters, and it has been found that a lower reward value rather than slower reward-based learning is responsible for anhedonia. These disruptions in reward processing in patients with depression are also linked to changes in brain activity in the anterior cingulate cortex and ventral striatum.

Furthermore, studies that have used tasks involving grip force and effort expenditure for rewards to distinguish between physical inability and a lack of motivation have found that patients experiencing apathy or anhedonia are reluctant to exert effort for any reward.

Cognitive control, which is also called executive function and is the goal-oriented flexibility in adaptive behavior, is also low in patients with depression, further indicating a reluctance to exert effort. Poor cognitive control is also linked to cognitive impairments in areas of memory and attention. Furthermore, neuroimaging studies have reported the link between neural networks and motivation, with lower connectivity between the anterior mid-cingulate cortex and supplementary motor area and increased effort sensitivity.

Moreover, the availability of the dopamine receptors D2 and D3 in the ventral striatum shows a negative correlation with anhedonia in patients with depression, along with low levels of dopamine transporter binding in the caudate, striatum, and putamen.

Inflammation has also been linked to motivational symptoms of depression. Systemic inflammation and an increase in pro-inflammatory cytokines have been associated with anhedonia, while treatments to lower inflammation have been beneficial in decreasing anhedonia in patients with depression. Furthermore, an increase in inflammation is also associated with reduced dopamine transmission and lower responses to rewards, which exacerbate depression symptoms such as anhedonia.

Exercise and depressive symptoms

Meta-analysis studies have found that aerobic exercises exert significant anti-depressant effects, with increased physical activity levels resulting in significant improvements in depressive symptoms. The reduction in depressive symptoms due to exercise has been comparable to those achieved through psychological therapies and anti-depressant medications. Physical activity has also been found to boost dopamine transmission and lower inflammation, which could play an important role in improving cognitive control and motivation.

Studies in Parkinson’s disease patients have shown that aerobic exercise results in immediate dopamine release in the striatum and increased reward sensitivity. The beneficial effects of exercise on cognitive control have also been observed to vary based on age, with older adults showing greater significant improvements in cognitive performance.

A better understanding of the potential mechanisms through which exercise exerts its antidepressant effects, such as decreased effort sensitivity, improved dopamine transmission, and reduced inflammation, could help in developing novel and tailored exercise interventions. A more personalized approach, where the interventions are designed to include exercises each patient enjoys, could further improve long-term adherence to the intervention.

Conclusions

Overall, the study showed that a lack of reward processing and increased effort sensitivity contribute significantly to apathy and anhedonia in patients with depression. These symptoms are also potentially linked to decreased dopamine transmission, increased inflammation, and lower cognitive control.

While aerobic exercise has been found to significantly benefit alleviating symptoms of anhedonia and reluctance to exert effort, the biological mechanisms through which exercise is beneficial remain unclear. The researchers believe that future studies involving larger sample sizes and randomized control trials would help uncover the mechanistic basis of exercise’s antidepressant effects.