Effect Of Antipsychotics On Serum Homocysteine Levels In First-episodic, Drug-naive Patients With Schizophrenia

Objectives To further clarify the relationship of serum homocysteine(Hcy) levels in the pathogenesis of schizophrenia. Explore whether homocysteine levels increased in the patients with schizophrenia; whether serum homocysteine levels in first-episodic drugna?ve patients with schizophrenia change after atypical antipsychotic treatment, whether homocysteine levels and psychotic symptoms are associated.Methods Fifty-six patients(21 men and 35 women) with schizophrenia, diagnosed by the consensus of two experienced psychiatrists according to the DSM-IV criteria(American Psychiatric Association, 1994), were recruited from Hui-Long-Guan Hospital, a city-run psychiatric hospital in Beijing, China. All patients included in the study were firstepisodic and drug-na?ve, age from 18-45, duration of illness must be less than or equal to 3 years, the total scales of Positive and Negative Syndrome Scale must be greater than or equal to 60,which was confirmed by collateral histories from family members. Complete medical histories, physical examination results, findings for laboratory tests including urine and blood screens, and electrocardiograms were obtained from all participants to rule out any neurological or other medical diseases(such as organic brain diseases, cardiovascular disease, and gastrointestinal absorption disorders). Other exclusion criteria also need to correspond. Fifty-six age- and gender-matched control subjects(21 men and 35 women) were healthy volunteers selected from Huilongguan communities during the same period. All patients received 12 weeks of atypical antipsychotic treatment. Patients’ psychopathological parameters were assessed with the Positive and Negative Syndrome Scale(PANSS) by two psychiatrists who had simultaneously attended a training session on the use of the PANSS before beginning the study. Serum Hcy levels of all subjects were measured by using enzyme linked immunosorbent assay(ELISA). Analysis of covariance(ANCOVA) was used to examine homocysteine differences between the two groups, with gender and diagnosis as independent variables, and age as a covariate. Paired t-test was used to compare serum homocysteine levels. Pearson’s correlation coefficient was used to evaluate the relationship between serum homocysteine levels and parameters including PANSS score, duration of illness, and age according to data distribution. Spearman’s correlation coefficient was used to evaluate the relationship between the reduction of serum homocysteine levels and parameters of PANSS score, Statistical analyses were conducted using the SPSS 13.0 statistical package for Windows. P< 0.05 was considered as statistically significant.Results The serum Hcy levels were higher in first-episodic drug-na?ve patients with schizophrenic than in controls(11.18 ± 4.53 vs 5.99 ± 3.61, F=37.195,df=1,P<0.001). Incomparision, we did not find any significant gender difference in serum homocysteine levels(P<0.001). Serum homocysteine levels were reduced after antipsychotic drug treatment in patients with schizophrenia(11.18±4.53 vs 8.98±4.07, t=3.857,P<0.001); but it was still higher than the normal controls, the difference was statistically significant(8.98±4.07 vs 5.99±3.61, F=13.393,P<0.001). At baseline, serum homocysteine levels of patients were positively correlated with the total PANSS scores(r=0.284,P= 0.034) and the scores of negative symptoms(r=0.515,P< 0.001) total PANSS scores. After 12 weeks of the atypical antipsychotic treatment, the serum homocysteine levels were negatively correlated with the scores of negative symptoms(r=-0.288,P=0.032), but not with the total PANSS scores(r=-0.220,P=0.103). After 12 weeks of the atypical antipsychotic treatment, the serum homocysteine levels were reducted 2.20±4.264μmol/L, the reduction of serum homocysteine levels were not correlated with the total PANSS scores(r=-0.066, P=0.483), the subscale scores for positive symptoms(r=0.057,P=0.542), negative symptoms(r=-0.022, P=0.810)and general psychopathology(r=-0.073, P=0.439). The serum homocysteine levels in patients were not correlated with age, body weight, BMI, gender, duration of illness and family history of mental illness.Conclusions Serum Hcy levels are elevated in patients with first-episode drug-na?ve schizophrenia. Serum Hcy levels are reducted by drug treatment,but still highter than health controls. Serum Hcy levels in patients with schizophrenia are related to negative symptoms of PANSS, but the specific performance and mechanisms are needed to be investaged by further researches.