Depression affects more than 168 million people worldwide and is one of the significant causes of disease. We understand that depression has substantial effects on overall health and wellness; however, evidence-based research on treating depression is still lacking. Now scientists are looking at our genes to develop new ways to manage mental health disorders. A recent study looks at how gene expression can help determine patients who are responsive to depression treatment. The research also demonstrates how those with treatment-resistant depression have higher inflammation levels throughout their system.
Knowing that inflammation levels are higher in those with severe depression and that some medications are not effective in treating these patients, reducing these levels could be even more critical in managing mental health disorders. This article highlights the gene expression study, what their findings mean, and how exercise can be a clinical tool to reduce inflammation and help regulate depression symptoms.
What Genes May Reveal About Depression
Advances in pharmacological treatment for clinical depression have made some strides in the past few years. However, even with these new treatments, those backed by evidence fall into two broad categories termed ‘somatic’ and ‘psychosocial.’ Psychology Today states the somatic category includes antidepressants and other medications, electroconvulsive treatment transcranial magnetic stimulation. Psychosocial treatments include various psychotherapy forms such as cognitive behavioral therapy. Scientists are still navigating this complex landscape, trying to find better ways to diagnose and treat depression, especially treatment-resistant depression (TRD).
TRD is a form of depression that doesn’t get better even after the patient has tried at least two antidepressant therapies. According to one study, while many factors play a role in developing depression and fatigue, both have been associated with increased immune system inflammatory activation. Understanding this mechanism of action, a new gene expression study published in Translational Psychiatry reveals it is now possible to distinguish between those with TRD and those with major depressive disorder (MDD) who respond to antidepressants based on inflammation levels.
The Groundbreaking Study
Lead author of the study, Dr. Annamaria Cattaneo from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London, states, “While there is evidence of increased inflammation in depression it is still unclear how exactly this occurs and what it looks like at the level of chemistry within the body.” The study examined the blood from 130 patients with MDD and 40 healthy controls to understand how gene expression can distinguish those patients with TRD from those who are responsive to medication.
Previous research has shown that high levels of C-reactive protein (CRP) in the blood indicate some degree of inflammation in the body. The study found higher CRP levels in both patients that were resistant to treatment and medication-free patients compared with patients with depression who were responsive to medication. The expression of several inflammation-related genes was also increased in both treatment-resistant and medication-free patients. The study showed for the first time that it is possible to distinguish patients with depression who do not respond to medication from those who are responding to drug therapy, based on the levels of inflammation and the presence of molecular mechanisms activating the inflammation.
The researchers also observed stronger signs of inflammation and stress in both the patients who were not responding to antidepressant treatment and patients who were medication-free, compared with patients who were responsive to medication and healthy controls. These findings support the growing evidence that patients that do not respond to antidepressants or have untreated depression have heightened inflammation compared with controls. So, where do patients and scientists go from here? These study’s findings could help towards developing personalized treatment therapies for depression. In the meantime, other tools should be considered, especially ones that reduce inflammation – including exercise.
Exercise as a Clinical Tool in Reducing Inflammation & Battling Depression
Though our understanding of the immunology underlying inflammation in depression is limited, it is crucial to address what is known and find ways to reduce inflammation. Anti-inflammatory agents, such as aspirin, statins, and antibiotics, have shown some promise in curbing the symptoms of MDD, according to a study in the Journal of Neurology Neurosurgery & Psychiatry. However, more studies are needed in this area. Exercise research shows more efficacy in reducing systemic inflammation – making it the most accessible tool in battling depression symptoms.
Studies reveal that inactivity causes many negative health issues and comorbidities, such as obesity and diabetes. However, inactivity also causes chronic inflammation, increasing the risk of disease and mental health disorders, including depression. Research affirms that regular exercise reduces fat mass and adipose tissue inflammation, which contributes to systemic inflammation. A study in Brain, Behavior, and Immunity found one 20-minute session of moderate exercise can stimulate the immune system, producing an anti-inflammatory cellular response. How is this possible? Exercise activates the hypothalamic-pituitary-adrenal (HPA) axis, the brain, and the sympathetic nervous system. Through HPA axis activation, cortisol and other hormones are released. According to one study, cortisol has potent anti-inflammatory effects, and catecholamines can inhibit pro-inflammatory cytokine production.
Research also demonstrates that aerobic training can downregulate toll-like receptors (TLRs). TLRs ignite the innate immune response, causing inflammation. Physical inactivity correlates with increased TLRs activation. Conversely, regular exercise can reduce the activation of the NLRP3 inflammasome and IL-1β, a cytokine processed by the inflammasome. Research also points to fighting Senescent cells to decrease inflammation. Senescent cells emit a mix of signals known as a senescence-associated secretory phenotype (SASP). These signals spur chronic inflammation, destroy tissues, and encourage nearby cells to become senescent. Exercise, especially muscle toning, can help clear out these cells, making way for healthy new ones.
By examining the above gene expression study, it is clear that there is an impact of inflammation on the brain, body, and behavior. This research opens an entirely new avenue for innovative strategies in treating depression – including exercise. Exercise may be the clinical tool needed to reduce inflammation in patients with severe depression, improve symptoms, and forge a clearer path to greater physical and mental health.
