Influence of the Cytochrome P450 Polymorphism on Clinical Response to Aripiprazole in Patients with Schizophrenia / 대한정신약물학회지

OBJECTIVE: Aripiprazole is an atypical antipsychotic drug metabolized partly by the hepatic cytochrome P450 enzyme, CYP2D6. The aim of this study was to investigate the influence of the CYP2D6 polymorphism on the pharmacokinetics of and clinical response to aripiprazole. METHODS: The study followed a prospective, multicenter, single-medication group design and involved a 26-week study of aripiprazole treatment in Korean patients with schizophrenia. Eighty-nine patients with schizophrenia were recruited and divided into 4 groups according to CYP2D6 genotype: homozygous extensive metabolizer (EM), heterozygous EM, intermediate metabolizer (IM), and poor metabolizer (PM). During the 26 weeks of the study, the pharmacokinetics of the blood samples was analyzed at week 3 and week 8 of drug administration. We used the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Barnes Akathisia Scale (BAS) for akathisia, the Simpson Angus Scale (SAS) for Par-kinsonism, the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia, and metabolic profiles as clinical measures. RESULTS: The sample was divided into 4 schizophrenia subgroups (homozygous EM, n=15; heterozygous EM, n=47; IM, n=22; PM, n=5). Pharmacokinetics analyses showed that patients with poorer functional alleles (PM) had smaller clearance and more than twice as long half-lives compared to those with homozygous EMs characterized by two functional alleles. PMs tended to show higher AUCs than EMs. Over the 26-week treatment period, however, no significant differences in the clinical responses (changes in the PANSS scores) were observed. The prevalence of extra-pyramidal symptoms (Parkinsonism, tardive dyskinesia, akathisia) did not differ among these groups despite the pharmacokinetic differences. CONCLUSION: Despite its relatively small sample size, this study suggested that the CYP2D6 polymorphism might not constitute the major factor contributing to the clinical response to and adverse effects of aripiprazole.

Thalamic Volume in Schizophrenia Patients, Subjects at Ultra-High Risk for Psychosis and Controls / 신경정신의학

OBJECTIVES: To investigate the changes in thalamic volumes in subjects at ultra-high risk (UHR) for psychosis. Subjects manifest changes which are similar to but different from those found in subjects with schizophrenia, and thalamic structural changes were often reported in schizophrenic subjects. METHODS: Thalamic volumes of 29 UHR subjects, 31 subjects with schizophrenia and 29 healthy controls, were measured from their T1-weighted coronal magnetic resonance (MR) images using manual tracing. RESULTS: UHR subjects showed greater right (6.243+/-0.848 cm3) and total (12.254+/-1.532 cm3) thalamic volumes compared to healthy control subjects (right thalamic volume=5.527+/-0.715 cm3, total thalamic volume=11.058+/-1.490 cm3) or patients with schizophrenia (right thalamic volume=5.855+/-0.938 cm3, total thalamic volume=11.513+/-1.784 cm3). The difference was significant for right (F=5.837, p=0.004) and total (F=4.217, p=0.018) thalamic volumes after intracranial volume had been accounted for as a covariate in ANCOVA. However, thalamic volume of subjects with schizophrenia showed no significant difference from controls. This difference was not affected by the presence of major depressive disorder or the magnitude of psychotic symptoms. Those among the UHR subjects taking antipsychotic agents did not show enlarged thalamic volume compared to controls. CONCLUSION: Our findings suggest that the possibility of a volumetric alteration of the thalamus characteristic of the UHR state.

Clinical Manifestations of Mycobacterium Tuberculosis Infection after Renal Transplantation / 대한이식학회지

PURPOSE: Transplant patients under immunosuppression are susceptible to mycobacterium tuberculosis infection. We analyzed renal transplant recipients, to evaluate the risk factors, clinical characteristics, and long-term outcomes of post- transplant tuberculosis (TB). METHODS: This study is based on the records of renal allograft recipients from October 1991 to June 2006 in two transplant centers in Korea. The demographic data, clinical manifestations, and long-term outcomes of this cohort of patients were retrospectively analyzed. RESULTS: Total 617 patients were enrolled in this study. Eighteen cases of TB (2.92%) occurred with a mean interval from transplant to diagnosis of TB of 33.1 (range: 1~121) months. Most of post-transplant TB were pulmonary TB (including pleural) (13/18), and extrapulmonary TB occurred in 5/18. There was no difference in the prevalence of diabetes mellitus, hepatitis B or C, and immunosuppressive agents between the patients who had developed post- transplant TB and who had not. However, there was higher incidence of acute rejection in post-transplant TB group (0.9+/-1.1 vs. 0.4+/-0.6, P=0.043), and post-transplant TB group had a tendency toward more past history of TB infection (P=0.096). Thirteen patients were successfully treated, 2 patients have been under treatment and 3 patients died. The patient survival was significantly reduced by post- transplant TB in multivariate analysis (relative risk=3.355, P=0.038). CONCLUSION: Post-transplant TB is a serious problem, which is associated with poor outcomes in renal transplant patients. Therefore, high index of suspicion is warranted to ensure early diagnosis and prompt initiation of treatment.