Clinical Significance of C-Reactive Protein in Major Depressive Disorder: Role of Dietary Pattern and Lifestyle Factors in the Disease Severity

Abstract

Major Depressive Disorder (MDD) is a global health challenge increasingly linked to systemic inflammation, with C-reactive protein (CRP) emerging as a key biomarker influenced by diet and lifestyle. This study aimed to evaluate CRP as a clinically relevant biomarker for identifying the inflammatory MDD subtype characterized by pro-inflammatory dietary patterns and suboptimal lifestyle habits. This cross-sectional study recruited 90 MDD patients (45 males, 45 females) from psychiatric clinics in Peshawar city and stratified into 3-groups by age (i.e., 18-30, 31-45 and 46-65 years). Their depression severity was assessed with Hamilton Depression Rating Scale (HAM-D, while CRP levels in their blood samples were measured using high-sensitivity immunoturbidimetric assays. The dietary intake of the subjects was evaluated through 24-hour recalls and a Food Frequency Questionnaire, and lifestyle factors including physical activity, sleep pattern, smoking, and electronic device use before sleep were assessed using standardized questionnaires. The data revealed that the CRP level in MDD male patients ranged from 2.40 to 7.80 mg/L whereas that of female patients ranged from 3.01 to 9.02 mg/L where in both cases the CRP level consistently increased with the age. The CRP levels in both genders were positively related with the disease severity where 84.2% male MDD patients and 91.1% female patients exhibited clinically significant CRP level (>3 mg/L) exceeding population prevalence rates. The 24-hour dietary recall showed that males consumed higher amounts of macronutrients (carbohydrates, protein, and fats), corresponding to 1953.3 kcal, compared to 1532.8 kcal in females. Both genders reported excessive intake of pro-inflammatory foods (i.e., processed food, red meat, sugary beverages and refined grains) and inadequate consumption of anti-inflammatory foods such as fruits, vegetables, whole grains, and omega-3 fish. The Dietary Inflammatory Index scores were +5.80 ± 2.90 for males and +8.6 ± 3.30 for females, with strong positive correlations between diet and CRP levels (r = 0.65 and 0.75, respectively). Lifestyle factors also influenced inflammation such as higher physical activity, good sleep quality (PSQI ≤ 5), non-smoking, and limited electronic device use were inversely related to CRP in both genders. Overall, females consistently showed higher CRP levels than males across all depression severity levels. These findings highlight the need for gender-specific lifestyle interventions that address sociocultural barriers and biological vulnerabilities contributing to women’s higher inflammatory burden in Khyber Pakhtunkhwa. Incorporating routine CRP testing and targeted anti-inflammatory strategies may improve personalized management of MDD in this population.