A Correlative Study Of The Psychosocial Factors And The Changes Of Serum Cytokines Levels In Treatment Resistant Depression Patients

Objective: The study investigated the psychosocial risk factors and mechanisms underlying dysregulations of hypothalamic-pituitary-adrenal (HPA) axis and cellular immune, and the effects of antidepressants on the cellular immune activity in treatment resistant depression patients.Methods: 30 treatment resistant depression patients, 30 treatment non-resistant depression patients and 30 normal controls were involved in the study. All the subjects themselves completed the following questionnaires: general condition questionnaire, EPQ, LES, SSRS, HAMD and HAMA were evaluated by the researcher. Cortisol, IL-2,IL-6 and TNF-αwere detected in all patients before and after a 6-week treatment with Paroxetine. Utilizing t test, x2 test, Pearson correlation, analysis of variance and stepwise regression analysis were used to statistic the collected data in SPSS 10.0.Results: (1) There were lower score of Extraversion and higher score of Neuroticism in TRD patients than TNRD patients and the normal group. The TRD patients showed significantly increased scores in negative life events and social intercourse problems, decreased total scores in social support and objective support. (2) The serum levels of cortisol, IL-6 and TNF-αin higher negative life events, lower social support, comorbid anxiety and severity TRD groups were significantly higher than that in TNRD patients.Those in lower negative life events , higher social support , non-comorbid anxiety and non-severity TRD groups were not significantly different from that of TNRD patients. (3) The serum levels of cortisol, IL-6 and TNF-αwere significantly lower after treatment in TRD and TNRD groups. But those in TRD patients were significantly higher than in TNRD patients before and after treatment. (4) There were longer course of disease and higher scores of HAMD and HAMA in TRD patients who failed to respond to antidepressants than TNRD patients. (5) The serum level of cortisol, IL-2 was positive correlation with the scores of negative life events. The serum level of IL-6 was positive correlation with the scores of negative life events, HAMD, HAMA, cognitive disturbance and somatic anxiety. The serum level of TNF-αwas positive correlation with the scores of HAMA and somatic anxiety. The total score of HAMD was positively related to the scores of negative life events, Pschoticism and Neuroticism of EPQ, negatively related to scores of social support, subjective support, objective support and utilization of social support. The total score of HAMA was positively related to the scores of negative life events and Neuroticism of EPQ, negatively related to scores of Extraversion of EPQ, social support and utilization of social support. (6) The factors which entered regression equation were as follows: In TRD patients, negative life events were the main risk factors of increased serum level of cortisol, IL-2, IL-6. Depression and anxiety were respectively the main risk factors of elevations in the serum level of IL-6, TNF-α. The negative life events and lower social support were the risk factors leading to depression. So was Neuroticism of EPQ leading to anxiety.Conclusions: Introversion, Neuroticism, experienced more negative life events, lower social support are the main risk factors of TRD. Stress and social support have actions on the severity, consequence for therapies and prognosis by the mechanisms of regulation of neuroendocrine and immune systems in TRD. Comorbid anxiety and depression exerts an influence on the immune modulation of TRD patients. The dysfunction of HPA axis and cellular immune activity may be involved in the pathophysiology of TRD. Paroxetine may attenuate depressive symptoms by restoring the negative feedback inhibition of the HPA axis, which is likely to be exerted through its effect on cellular immune activity system.