Plasma Orexin-A Levels In Schizophrenics And The Effects Of Antipsychotic Therapy

The pathophysiology of Schizophrenia is still unknown. For many years the vastmajority of the study in pathogenesis of schizophrenia is still neurotransmitters.The orexinsare endogenous neuropeptide synthesized in hypothalamic neurones and they werediscovered in1998. They play a major role in the regulation of feeding, sleep/wakeful-ness,endocrine function,substance dependence,central reward, breathing,learning andmemory and so on.With the development of research, abroad research had evidencedthat the hypothalamic orexin system directly and strongly innervated and potently excitednoradrenergic, dopaminergic,serotonergic,histaminergic and cholinergic neurons.Orexinsalso play a major role in modulating the release of glutamate and other amino acidtransmitters. Orexins can adjust the dopamine pathways in the cortex. There werepublished data that linked disturbances in orexins with psychiatric disorders.Objective: To study the plasma orexin-A level in schizophrenics and the effectsof antipsychotic therapy and the clinical significance.The first part:Methods:We Selected61first episode and drug-naive schizophrenic patientsas the study group.37healthy cases as the control group which matched thestudy group.We collected all participants’ venous blood samples in the morning at6:00a.m. after12h of fasting and we measured their plasma orexin-A level byradioimmunoassay.Results:There was no significant difference in plasma orexin-A level betweendrug-naive and first episode schizophrenics [(67.35±59.81) pg/ml] and normalcontrol group[(50.45±71.15)pg/ml](P>0.05).The second part:Methods: We Selected20drug-naive and first episode schizophrenic patientswho continuous using olanzapine (20mg/day), before treatment and after12months treatment,we measured the orexin-A level of plasma,weight,fasting blood glucose,serum triglyceride,cholesterol,HDL and LDL level.Treatment response was assessedby PANSS before treatment，4，8weeks and12months of treatment.Results:①After the treatment of olanzapine for12months, schizophrenicpatient’s plasma orexin-A level decreased significantly [(68.67±60.31）pg/ml VS(39.83±18.12）pg/ml，P<0.05]; Weight, BMI, triglycerides, total cholesterol,andfasting plasma glucose level,LDL were increased signifeicantly,and HDL decreasedsignificantly(P<0.05).②The decrease of Orexin-A level were positively correlatedto the change of LDL (r=0.483, P=0.03).③There was a significant negativecorrelation between weight gain and the change of the PANSS positive scores(r=0.603, P<0.01);Weight gain wasn’t signifycantly correlated with the change ofOrexin-A level (r=0.061, P>0.05).④PANSS total,positive,negative scores decreasedsignificantly with12months of olanzapine treatment,(P<0.01). The total effectiverate was90perent.Conclusion: There was no significant difference in plasma orexin-A level betweendrug-naive and first episode schizophrenic patients and normal controlgroup(P>0.05).Olanzapine has significant effects on patient’s Orexin-A，weight,glucoseand lipid metabolism. Weight gain and the change of the PANSS positive scores weresignificantly and negatively correlated.It can be speculated that weight gain was closelylinked with the effect of olanzapine in the positive symptoms. Weight gain wasn’tsignificantly correlated with the change of Orexin-A level, we were not sure that thereduce of Orexin-A level was the cause of the weight gain.Olanzapine is useful in thefirst episode schizophrenic, it can treat positive and negative symptoms.