Inflammation and Mental Health: The Hidden Link Behind Depression and Psychosis

Written By Dr. Nicholas Hatcher

Most people think of inflammation as something that occurs after a sprained ankle or during an infection. However, emerging research suggests that the same biological process may also contribute to depression, psychosis, and other psychiatric conditions (Miller & Raison, 2016).

In recent years, scientists have uncovered a compelling connection between chronic low-grade inflammation and mental health disorders, fundamentally changing how clinicians understand, evaluate, and treat these conditions.


What is inflammation, and how does it impact the brain?

Inflammation serves as the body’s natural defense system. Under healthy circumstances, it is a short-lived response: the immune system becomes activated in response to injury or infection and then returns to baseline. Problems arise when inflammation becomes chronic and low-grade, persisting silently over time without the typical signs of redness or swelling (Raison, Capuron, & Miller, 2006).

This persistent inflammatory state interferes with normal cellular processes, including those within the central nervous system. Elevated levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), have been shown to alter neurotransmitter metabolism, reduce neuroplasticity, and dysregulate the hypothalamic-pituitary-adrenal (HPA) axis, which governs the stress response (Haroon, Raison, & Miller, 2012). These disruptions are increasingly linked to symptoms such as low mood, cognitive impairment, fatigue, and even psychotic features.


Inflammation and treatment resistance in depression.

One of the most important findings in contemporary psychiatry is that inflammation can reduce the effectiveness of serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs). Studies have demonstrated that individuals with elevated inflammatory markers, particularly high-sensitivity C-reactive protein (hsCRP), are less likely to achieve remission with standard antidepressant therapy (Uher et al., 2014).

For example, hsCRP levels exceeding 3 mg/L have been associated with a diminished response to SSRIs. This may be due to inflammatory cytokines impairing serotonin synthesis, enhancing its reuptake, and promoting glutamate-mediated neurotoxicity, all of which contribute to mood and cognitive symptoms (Haroon et al., 2012; Miller & Raison, 2016). As a result, clinicians are increasingly using hsCRP as a biomarker to help guide personalized treatment planning.


Strategies for reducing inflammation to support mental health

Addressing inflammation does not replace psychiatric medications but rather enhances overall treatment by targeting an important underlying contributor. A comprehensive approach typically involves nutrition, targeted supplementation, lifestyle modifications, and the management of physiological contributors.

1. Nutrition

An anti-inflammatory diet emphasizes omega-3-rich foods, high-fiber vegetables, fruits rich in polyphenols (such as berries), and minimizes processed foods. Such dietary patterns have been linked to reductions in depressive symptoms and systemic inflammation (Lassale et al., 2019).

2. Targeted supplementation

Nutrients such as omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), have shown benefit in treating depression, especially when inflammation is elevated (Mocking et al., 2016). Other promising agents include N-acetylcysteine (NAC), which supports glutathione production, and curcumin, a compound in turmeric with anti-inflammatory properties (Morris et al., 2017).

3. Lifestyle interventions

Regular moderate exercise has been shown to lower inflammatory cytokines and increase brain-derived neurotrophic factor (BDNF), supporting mood regulation (Eyre et al., 2013). Mind-body practices such as meditation, yoga, and breathwork help reduce HPA axis hyperactivity and stress-related inflammation (Pascoe, Thompson, Jenkins, & Ski, 2017). Ensuring adequate and high-quality sleep is also critical, since sleep disruption can both result from and contribute to chronic inflammation (Irwin, 2019).

4. Addressing underlying contributors

Additional strategies might include treating gut dysbiosis, which is increasingly recognized as a driver of systemic inflammation via the gut-brain axis (Dinan & Cryan, 2017), as well as investigating autoimmune or chronic infectious processes when indicated.


How an integrative psychiatry specialist can help.

An integrative psychiatry specialist is uniquely equipped to explore these dimensions. Instead of focusing solely on diagnostic criteria and symptom checklists, integrative practitioners assess how inflammation, hormonal balance, nutritional status, stress physiology, and life experiences interconnect to shape mental health. Laboratory tests, including hsCRP and cytokine panels, can provide valuable information to tailor interventions more precisely.

This root-cause approach moves beyond asking “What is the diagnosis?” to explore “What is driving this unique pattern of distress?” Through this lens, treatment becomes highly personalized, often blending conventional pharmacotherapy with nutraceuticals, lifestyle modifications, psychotherapy, and stress regulation techniques to address each layer contributing to the individual’s experience.


Final thoughts.

If you or someone you care about is struggling with depression or psychosis that has not improved with standard approaches, it may be worthwhile to consider whether chronic inflammation is part of the picture. By addressing the mind and body as an integrated system, patients and clinicians can work together toward more durable and meaningful recovery.

For those interested in exploring this pathway, an integrative psychiatric assessment can help identify hidden contributors and create a personalized plan designed to foster long-term mental wellness.


Dr. Nicholas Hatcher
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