Decreased Plasma Glial Cell Line-derived Neurotrophic Factor(GDNF) Level In Major Depressive Disorder Is Associated With Age And Clinical Symptom Severity

Objective: Depression is one of the most prevalent disabling disorders worldwide.However,the pathophysiological process of depression is still unclear.The neurotrophic hypothesis implicated the decreased neurotrophic factors in the stress-induced depression and proposed that antidepressant could restore such abnormality.Glial cell line-derived neurotrophic factor(GDNF)is able to promote the growth,proliferation,differentiation,and survival of multiple neurons.GDNF level changes in the peripheral blood has been reported in patients with MDD.Most frontal connections and gray matter structures do not mature until young adult.Clinical features,recurrence rates and suicide rates are significant different in major depressive disorder(MDD)according to age.In this study,we aimed to investigate whether GDNF levels differentiated within various age groups and its relationship with age/clinical severity.Methods: The study enrolled MDD subjects(n=69)within age 13 to 45 years from the Department of Psychiatry,First Affiliated Hospital of China Medical University。healthy controls(HC)(n=99,age 13–45 years)were recruited from social society by advertisement.MDD subjects and healthy controls(HC)are divided into younger(age 13–24 years)group(yMDD n = 35,yHC n = 44)and older(age 25–45 years)group(oMDD n = 30,oHC n = 55)based on the age of brain maturity.Blood samples were withdrawn into evacuated tubes between 10 am and 2pm.After collection,samples were centrifuged to separate plasma.The concentrations of plasma GDNF were determined by Magnetic Luminex Assays.Clinical symptom severity was evaluated using the Hamilton Depression Rating Scale(HAMD-17)and the Hamilton Anxiety Rating Scale(HAMA-17)by two trained psychiatrists.HAMD<7 is defined as with no depressive symptom,7≤HAMD<17 as partial remission or possibility of depression symptom,HAMD≥17 and corresponding with DSM-Ⅳ MDD criteria as current depressive state.Compared the levels of plasma GDNF between subgroups and analyzed the correlation between GDNF levels and HAMD/HAMA scores.Results: Plasma GDNF levels in yMDD patients were significantly decreased compared to yHC(yMDD 1.55 ± 0.46pg/ml,yHC 1.77 ± 0.47pg/ml,p<0.05).Such difference was not found between oMDD group and oHC group(oMDD 1.69±0.41 pg / mL,oHC 1.70±0.48 pg / ml,t=0.12,p = 0.90).Moreover,significant GDNF differences between yMDD and oMDD,yHC and oHC were not found.In correlation analysis,we did not find correlation between age and GDNF levels in all MDD patients(r=0.054,p=0.668),present MDD patients(r=0.299,p=0.188)or in HC subjects(r=-0.126,p=0.213).Significant difference of GDNF levels in MDD subjects was not found between onset and remitted state(onset 1.67 ± 0.44pg/ml,remitted 1.52 ± 0.43pg/ml,p=0.21),with and without antidepressants(antidepressant treatment 1.61±0.45pg/ml,antidepressant-na?ve 1.62±0.42pg/ml,p=0.98).Our results also showed negative correlations between plasma GDNF levels and HAMD/HAMA scores(r=-0.33,p<0.05;r=-0.39,p<0.05).Conclusion: We innovatively divided MDD subjects into two groups by the age of brain maturity and found the GDNF expression existed age distinction of MDD subjects,suggesting that GDNF may be involved different pathophysiology of MDD in different age.Applying foundation for further studies researching different GDNF effect of various age on MDD.