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.

University of Michigan - Ann Arbor

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

Exercise and biological mechanisms in mood

Paolucci, E. M., Loukov, D., Bowdish, D., & Heisz, J. J. (2018). Exercise reduces depression and inflammation but intensity matters. Biological psychology, 133, 79–84. https://doi.org/10.1016/j.biopsycho.2018.01.015

Exercise reduces depression and inflammation but intensity matters 

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.

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