ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Genetic variations in drug-metabolizing enzyme genes change drug pharmacokinetics and response. CYP2C19 is a clinically important enzyme that metabolizes citalopram (CIT). The objective of this study was to determine CYP2C19 genetic polymorphisms and to evaluate the impact of these polymorphisms on the metabolism of citalopram in a sample of the Turkish population. We also assessed *17 polymorphism in healthy subjects in this population. METHODS: The CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (209 healthy individuals and 50 patients for CIT metabolism), and the plasma concentrations of CIT and demethylcitalopram (DCIT) were quantified by high-performance liquid chromatography. RESULTS AND DISCUSSION: The CYP2C19*1 and *17 allele frequencies for the patient group and the healthy group were 71·0%, 18·0% and 81·1%, 18·9%, respectively. There was no significant difference between the two groups (P > 0·05). The mean plasma concentrations and the mean dose-corrected (C/D) plasma levels of DCIT were significantly higher in patients with the CYP2C19*1/*1 genotype compared to patients with CYP2C19*1/*2 and CYP2C19*2/*2 genotypes (P < 0·05). Furthermore, the mean metabolic ratio (MR, CIT/DCIT) was also significantly higher in the CYP2C19*1/*2 + CYP2C19*2/*2 genotypes (P < 0·05). On the other hand, plasma CIT, DCIT concentrations and M/R value in the CYP2C19*1/*1 genotypes were no different to those of the CYP2C19*1/*17 genotypes (P > 0·05). WHAT IS NEW AND CONCLUSION: Our data suggest that CYP2C19*17 polymorphism does not have a significant effect on CIT metabolism. In contrast CYP2C19*2 polymorphism has a prominent role and is likely to contribute to interindividual variability in CIT metabolism in vivo at therapeutic doses.
Subject(s)
Citalopram/metabolism , Citalopram/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Polymorphism, Genetic/genetics , Adult , Aged , Citalopram/analogs & derivatives , Depressive Disorder, Major/metabolism , Dose-Response Relationship, Drug , Female , Gene Frequency/genetics , Genotype , Humans , Male , Middle AgedABSTRACT
BACKGROUND AND PURPOSE: One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS: NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by (1)H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17-38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS: Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = -2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = -1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = -1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS: Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores.
Subject(s)
Aspartic Acid/analogs & derivatives , Asperger Syndrome/diagnosis , Asperger Syndrome/metabolism , Choline/metabolism , Gyrus Cinguli/metabolism , Magnetic Resonance Spectroscopy , Adolescent , Adult , Aspartic Acid/metabolism , Asperger Syndrome/complications , Diagnostic and Statistical Manual of Mental Disorders , Humans , Male , Obsessive-Compulsive Disorder/complications , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/metabolism , ProtonsABSTRACT
OBJECTIVE: The aim of this study was to determine the effect of stressful life events on the onset and exacerbation of psoriasis, depression, anxiety, life satisfaction and affective expression levels in psoriasis patients and psychological risk factors related to psoriasis. METHOD: Fifty psoriasis patients were examined dermatologically and psychiatrically and then administered the Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Scale (STAI I-II), Life Satisfaction Scale (LSS), Courtauld Emotional Control Scale (CECS) and Body Image Satisfaction Scale (BIS). Symptom severity was measured by the Psoriasis Area Severity Index (PASI). RESULTS: Thirty-four patients declared that they had had a psychologically stressful life event in the last 3 months prior to the beginning of the illness. The mean PASI score was 1.75+/-1.65; BDI score 13.58+/-6.11; STAI-I score 39.54+/-9.18, STAI-II score 46.58+/-8.05; LSS score 9.18+/-4.39; CECS score 51.64+/-9.75; BIS score 93.74+/-16.67. CONCLUSION: Psoriasis patients reported significantly higher degrees of depression and more body cathexis problems than controls. In addition, the risk for developing psoriasis increased significantly in patients with moderate and severe depression. We also found a relationship between symptom severity and low affective expression and high BDI scores in this study. These findings suggest that the relationship between psoriasis and psychological problems can be reciprocal and requires further investigation.
