Hyperactivation of inflammatory response in depressed patients with psychomotor retardation

Introduction: There is abundant evidence that depression involves alterations in multiple aspects of immunity that may contribute to the development or exacerbation of a number of medical disorders and also may play a role in the aetiology of depressive symptoms. Moreover, major depression appears to be associated with increased plasma concentrations of cytokines and C-reactive protein (CRP), a marker used to emphasize low-grade inflammation and to predict cardiovascular events in patients with coronary heart disease. The aim of our study was to investigate the relationship between plasma concentrations of CRP and psychopathological features in depressed patients during an acute phase of illness. Methods: 134 drug-free patients (M/F = 63/71; mean age 47,14 ± 16,42) with a Major Depressive Disorder (MDD) during a Major Depressive Episode (MDE) and 38 controls (M/F = 29/9; 42,56 ± 10,63) have been recruited at the Day Clinic of Psychiatry of the Catholic University of Sacred Heart in Rome. A blood sample for the determination of plasma CRP levels was collected before starting treatment. Severity of depressive and anxiety symptoms was measured with 21-HDRS (21 Item - Hamilton Depression Rating Scale) and HARS (Hamilton Anxiety Rating Scale). Anhedonia, psychomotor retardation and aggression were evaluated by SHAPS (Snaith Hamilton Pleasure Scale), DRRS (Depression Retardation Rating Scale) and AQ (Aggression Questionnaire). The levels of CRP were measured using a nefelometric system. Mann-Whitney U test was used to determine group difference in CRP values. Results: CRP levels were significantly increased in depressed patients (3,07 ± 4,82 vs. 1,18 ± 1,20; p=0,002). No significant correlation between C-Reactive Protein values and severity of depressive and anxious symptoms has been observed. After controlling for age, CRP levels were significantly correlated to DRRS scores (r: 0,22; p=0,015). Patients with higher psychomotor retardation scores (DRRS>11) also showed higher CRP levels (3,87±6,14 vs. 2,10±2,58; p<0,05) in comparison to patients with lower retardation scores (DRRS<11). Conclusions: A strong evidence indicates that major depression may be accompanied by an activation of inflammatory, autoimmune and cell-mediated responses. In our sample, according to previous data, a dysfunction of inflammatory response have been reported. The major finding of our research is that a psychopathological profile characterized by psychomotor retardation has been significantly correlated to higher CRP levels. Historically, psychomotor disturbances have been regarded as essential and measurable features of major depressive disorder that also contribute to the nosology of the melancholic subtypes. Furthermore, systemic infections commonly cause sickness symptoms including psychomotor retardation. Recent findings also demonstrate an interaction between inflammation and neurocognitive performance, specifically implicating the influence of circulating cytokines on dopaminergic dysfunction in mediating the psychomotor consequences of systemic infection. Further research is needed to clarify the involvement of immune variables in major depression and the relationship between inflammation and monoaminergic deregulation.