Systemic low-grade inflammation associated with specific depressive symptoms: insights from network analyses of five independent NHANES samples

Abstract

To the editor: Major depressive disorder (MDD) is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters, hypothalamic–pituitary–adrenal axis, immune-inflammation and the glutamate system.1 Numerous meta-analyses have reported that patients with MDD have a higher level of peripheral and cerebrospinal inflammatory markers, including C- reactive protein (CRP), interleukin 1beta (IL-1β), IL-6 and tumour necrosis factor-alpha (TNF-α).2 3 CRP, as an acute marker of reactant, is the most well-studied biomarker of MDD; numerous investigations revealed that elevated CRP was linked to core symptoms of MDD, including increased depressive mood4 and greater anhedonia.5 Several studies also have discovered links between CRP and cognitive symptoms (eg, difficulty concentrating)6 and suicidal behaviours.7 Moreover, CRP is more commonly reported in association with neurovegetative symptoms, including fatigue or loss of energy, changes in appetite and sleep problems.6 The association between CRP and specific symptoms remains unknown; uncovering specific symptoms driven by CRP could help identify the possible inflammatory subtypes of depression to pave the way for more specific anti-inflammatory treatments. The data for this secondary analysis was derived from five National Health and Nutrition Examination Survey (NHANES) samples (2005–2006, 2007–2008, 2009–2010, 2015–2016 and 2017–2020). NHANES encompasses nationally representative community samples within the USA, and the surveys are designed to examine the nutritional status and physical and mental health. NHANES has been conducting ongoing 2-year cycles of surveys of a representative, stratified, multistage probability sample of the US population since 1999. Each wave of surveys recruits a different set of participants. Those who were chosen and consented to participate completed a computer-assisted interview done in their homes by trained staff. Following the home interview, all tests (including the blood draw) and additional interviews (including the assessment of depressive …