The negative acute phase response and not serum C-reactive protein is a major biomarker of major depression: a precision nomothetic psychiatry study

BackgroundRecently, it was suggested that serum high-sensitive C-reactive protein (hsCRP) serves as a biomarker for "inflammatory major depression (MDD)" when serum hsCRP exceeds > 3.0 mg/L. Since 1991-1992, it has been known that MDD is characterized by a negative acute phase protein (APP) response with lowered serum albumin and transferrin levels. AimsTo compare hsCRP with negative APPs as biomarkers of MDD and the severity of physio-affective symptoms and to clarify their relationship with immune and metabolic variables. MethodsThis case-control study included 125 MDD patients and 40 healthy controls and assessed serum hsCRP, albumin, transferrin, M1 macrophage profile, and the compensatory immunoregulatory system (CIRS). ResultsNo significant elevations in hsCRP levels in MDD compared to controls were found. A minority of MDD patients (15.2%) had hsCRP values higher than 3 mg/L, and 78.9% of those had concentrations between 3 and 7 mg/L. Serum hsCRP is largely associated with metabolic parameters, including metabolic syndrome and body mass index (BMI), and with adverse childhood experiences (ACEs), M1 macrophage profile (all positively), and CIRS (inversely). Serum transferrin and albumin are significantly reduced in MDD with an accuracy of 77.3%. Both proteins are strongly and inversely correlated with the physio-affective phenome of MDD, ACEs, and immune activation. ConclusionsMDD is accompanied by non-classical inflammation with a negative APP response associated with immune activation and ACEs. Many MDD patients with hsCRP values <3 mg/L show indicants of a smoldering negative acute phase response. Increased hsCRP does not indicate "inflammatory depression."