Volume 29, Issue 163, September 2025

Inflammation and Depression: Biological Links and Implications for Treatment Response

Strzałkowska Antonina^1♦, Czyż Paweł², Janowski Maciej¹, Górska Marta¹, Górski Jakub³

¹Central Teaching Hospital of Medical University of Lodz, Pomorska 251, 92- 213, Lodz, Poland
²Szpital Miejski im. Św. Wincentego a Paulo w Gdyni, ul.Wójta Radtkego 18 Gdynia, Poland
³Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland

^♦Corresponding author
Antonina Strzałkowska, Central Teaching Hospital of Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland

ABSTRACT

Research from the last two decades indicates that inflammation plays a substantial role in the pathogenesis of depression. Numerous studies have reported elevated levels of pro-inflammatory markers, including C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Tumour Necrosis Factor-alpha (TNF-α), in individuals diagnosed with Major Depressive Disorder (MDD). These findings appear to be more pronounced in cases that are treatment-resistant. Chronic inflammation affects mood through several biological mechanisms. It disrupts the Hypothalamic- Pituitary-Adrenal (HPA) axis stress response, resulting in sustained cortisol secretion and chronic hypercortisolaemia. Ongoing immune activation downregulates the expression of Brain-Derived Neurotrophic Factor (BDNF), a protein essential for neurogenesis and plasticity. Inflammation impairs serotonin synthesis and signalling, which negatively affects mood, appetite, and sleep. Collectively, these biological changes alter the function of synaptic pathways involved in emotional regulation and stress management, particularly the prefrontal cortex and the amygdala. In this narrative review, we aim to emphasise the role of inflammation in depression pathophysiology and explore whether addressing inflammation through pharmacological and lifestyle interventions could alleviate depressive symptoms. We conducted a structured narrative search focusing on adult MDD and examined observational cohorts, longitudinal and Mendelian randomisation studies, neuroimaging, experimental inflammation paradigms, and randomised trials of anti-inflammatory augmentation. Overall, the findings suggest an inflammatory contribution in a subset of patients, with modest and heterogeneous effects. Stratifying potential candidates for anti-inflammatory treatment will require researchers to use standardised biomarker assessments, carefully control confounders, and conduct stratified, adequately powered studies that integrate lifestyle modification with targeted anti-inflammatory approaches while monitoring safety.

Keywords: Inflammation, Depression, Pro-inflammatory cytokines, Treatmentresistant depression

Medical Science, 2025, 29, e178ms3706

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DOI: https://doi.org/10.54905/disssi.v29i163.e178ms3706

Published: 25 September 2025