Physical activity leads to an increase in brain-derived neurotrophic factor (BDNF) in the hippocampus. BDNF is one of the main contributors to neurogenesis, the formation of neurons. Antidepressants play a similar role in enhancing BDNF production. BDNF can promote behavioral recovery when administered by itself in rat models of depression.

Exercise and neurogenesis

* Dopamine: exercise increases levels of dopamine and its affinity to dopamine receptors, while promoting neuroprotection for dopaminergic neurons.
* Norepinephrine: exercise can reduce activation of the norepinephrine system, which is linked to stress. Release of NE to the amygdala and frontal cortex are inhibited, reducing anxiety. On the other hand, exercise can increase NE levels in the brainstem and spinal cord to promote cognitive function (ex. memory consolidation and retrieval).
* Serotonin: exercise can lead to increases in serotonin (5-HT) in the hippocampus, amygdala and cortex, and are dependent on exercise intensity. These increases are linked to improvement in cognitive function and fatigue.

Exercise and neurotransmitters

The hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) play roles in the stress response and the production of glucocorticoids (cortisol) and epinephrine, respectively. Exercise is a form of stress, requiring greater energy supply in somatic tissues, and activates both the HPA axis and SNS. Glucocorticoids promote gluconeogenesis - glucose synthesis - in the liver, while epinephrine stimulates ATP production. Exercise is not associated with fear or threat like psychological stress, so there must be some underlying differences.

Exercise and stress response

Paolucci et al. (2018) looked into the relationship between exercise and pro-inflammatory cytokines in college students, as measured from blood samples. Moderate intensity exercise lowers levels of the cytokine TNF alpha, which is thought to contribute to depression. High intensity exercise did not significantly lower TNF alpha, showing that it increases stress despite reducing depressive symptoms. The difference between intensities was even more apparent with the cytokine IL-6.

Exercise and inflammation

Exercise affects several biological mechanisms that are associated with depression, and can alter relevant brain structures.

University of Michigan - Ann Arbor

Exercise has widely been reported to enhance positive mood and reduce negative mood, based on self-reported questionnaires. The effects of exercise on mood is immediate and continues for about one day. Its benefits are maximized when subjects find the type of physical activity enjoyable.

Exercise and mood

Firth, J., Stubbs, B., Vancampfort, D., Schuch, F., Lagopoulos, J., Rosenbaum, S., & Ward, P. B. (2018). Effect of aerobic exercise on hippocampal volume in humans: A systematic review and meta-analysis. NeuroImage, 166, 230–238. https://doi.org/10.1016/j.neuroimage.2017.11.007

Effect of aerobic exercise on hippocampal volume in humans: A systematic review and meta-analysis 

Subjects show increases in alpha oscillations after exercise, which indicate decreased activation of the cortex (relaxation, low anxiety, fatigue). There are also increases in theta power, which is associated with greater acetylcholine in the hippocampus and plasticity.

Exercise and mood: effects on EEG

The mood benefits of exercise are independent of exercise intensity. Light exercise can have similar effects as intense exercise in improving mood in major depressive disorder. In this study, depression level was quantified using the Profile of Mood States (POMS) questionnaire.

A different study, Paolucci et al. (2018), with a sample of college students showed that moderate continuous training is the most beneficial for mental health, compared to high-intensity interval training and no training. 

Exercise intensity and mood

The ability for physical exercise to substitute for antidepressant medication has been explored. It would be a promising alternative due to the lack of side effects that are associated with exercise compared to medication. The effectiveness of exercise is initially similar to medication, but over a long period of time, medication tends to be more effective (despite its side effects). However, combining antidepressant therapy with exercise provides greater benefits to patients with depression.

Exercise as an antidepressant

No significant difference has been observed between aerobic and anaerobic exercise in reducing depression. Both types of exercise are sufficient to improve symptoms of depression. In the cited study, running on a treadmill was the aerobic exercise, while lifting weights was the anaerobic exercise.

Exercise type and mood

Exercise and biological mechanisms in mood

* Exercise can promote brain remodeling through epigenetic effects (reversible changes in gene expression without altering DNA base pairs). 
* Histone modification - a form of gene transcription regulation - after exercise often occurs through activation of HAT and inactivation of HDAC, which is shown to increase cognitive function and memory formation in rats. 
* DNA methylation is influenced by exercise and can lead to improved cognitive function, upregulation of BDNF, downregulate the p75 receptor linked to cell death.
* Chromatin remodeling also occurs at the Bdnf gene to increase BDNF production.
* Changes in the prevalence of certain microRNAs take place to promote cognition and neurogenesis.

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