Gene Frequency of CYP2D6*4 and *10 Variants in Karachi Population

Author(s):  
Tamkeen Fatima ◽  
Farah Zeb ◽  
A. Dar Farooq

Background: CYP2D6 is to be considered the most pronounced gene in pharmacegenetic field which is involved in metabolizing ~25% of all clinically used neuroleptic drugs and other antidepressants. We designed a study to evaluate differential expression of CYP2D6*4 and CYP2D6*10 variants which are very prevalent in Asian countries and exhibit variation in drug metabolizing ability that affect therapeutic responses. Objective: The purpose of this study is to determine the genotypic frequencies of CYP2D6 *1 (normal metabolizer), *4 (poor metabolizer) and *10 (intermediate metabolizer) variants among schizophrenic subjects and compared with control group from a sub-set of Karachi population. Method: Genomic deoxyribonucleic acid (DNA ) was extracted and amplified with CYP2D6*4 and *10 primers using polymerase chain reaction (PCR) and digested by Bacillus stereothermophilus (BstN1) and Hemophilus parahemolyticus (Hph1) restriction enzymes. The digested bands were identified as wild type or mutants and their genotypic frequencies were estimated statistically by Hardy-Weinberg equation (HWE) and analyzed further under non-parametric Chi-square test. Results: The results mentioned the frequencies of CYP2D6*1 wild allele (57%) which produces functional enzyme in normal subjects but CYP2D6*4 variant (9%) that produces non-functional enzyme and CYP2D6*10 allele (70%) produces altered enzyme with reduced activity that was most prevalent in schizophrenic patients. Conclusion : Genotyping of CYP2D6 alleles among schizophrenic patients indicated prevalence of *4 and *10 variants in Karachi population producing non-functional and reduced functional drugs metabolizing enzymes respectively that increases the incurability rate of schizophrenia. Therefore, CYP2D6 gene screening program should be conducted routinely in clinical practice to help clinicians to prescribing appropriate doses according to patient’s genotype and minimize the sufferings of schizophrenia. Discussion: In last, drug response is a complex phenomenon that is dependent on genetic and environmental factors. CYP2D6 polymorphism may un-cured the schizophrenia due to improper drug metabolism and protein-proteins interaction that may alter the antipsychotic drugs metabolism among patients with variable drug resposes. Gene testing system need to establish for analyzing maximum patient’s genotypes predicted with poor metabolizer, intermediate metabolizer and ultrarapid metabolizer for the adjustment of antipsychotic drugs.

2003 ◽  
Vol 62 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Marek Nieznanski

The aim of the study was to explore the basic features of self-schema in persons with schizophrenia. Thirty two schizophrenic patients and 32 normal controls were asked to select personality trait words from a check-list that described themselves, themselves as they were five years ago, and what most people are like. Compared with the control group, participants from the experimental group chose significantly more adjectives that were common to descriptions of self and others, and significantly less that were common to self and past-self descriptions. These results suggest that schizophrenic patients experience their personality as changing over time much more than do healthy subjects. Moreover, their self-representation seems to be less differentiated from others-representation and less clearly defined than in normal subjects.


1980 ◽  
Vol 50 (2) ◽  
pp. 371-375
Author(s):  
Milton Turbiner ◽  
Robert M. Derman

This study was designed to assess the discriminative capacity of a visual-searching task for brain damage, as described by Goldstein and Kyc (1978) , for 10 hospitalized male, brain-damaged patients, 10 hospitalized male schizophrenic patients, and 10 normal subjects in a control group, all of whom were approximately 65 yr. old. The derived data indicated, at a statistically significant level, that the visual-searching task was effective in successfully classifying 80% of the brain-damaged sample when compared to the schizophrenic patients and discriminating 90% of the brain-damaged patients from normal subjects.


2019 ◽  
Vol 21 (4) ◽  
pp. 254-257
Author(s):  
JB Khatri ◽  
BK Goit ◽  
A Subedi

An intelligence deficit in schizophrenia is common and is associated with relapse and occupational impairment. The study aims to examine the intelligence quotient of schizophrenic patients and to compare with those of general population. This was a case control study where 30 adult schizophrenic patients between 15 to 45 years were enrolled from the inpatient and outpatient Psychiatry Department of Manipal College of Medical Sciences, Pokhara, Nepal. For control group, 30 normal subjects were enrolled from the general population matched with case group. The intelligence quotients were assessed by Wechsler Adult Intelligence Scale. The prevalence of intelligence deficit was 76.7% in the schizophrenic patients. The mean intelligence quotient was 84.80 with standard deviation of 6.53 in patients with schizophrenia. The intelligence quotient was average or above average in all the general populations. The mean intelligence quotient was 110.63 with standard deviation of 8.74 in the general population. The study concluded that the schizophrenic patients performed poorer in intelligence quotient than the general population


Author(s):  
Tamkeen Fatima

CYP2D6 gene polymorphism is considered a main obstacle in the process of drug metabolism under clinical diseases that affect pharmacokinetics of ~25% of antidepressants and other drugs. Inter-individual variation occurs in the amount and functional activity of CYP2D6 enzyme produce undesirable side effects. The primary aim of current research is to evaluate gene and genotypic frequencies of CYP2D6 *1 extensive metabolizer, *4 poor metabolizer and *10 intermediate metabolizer allelic variants among depressed patients and compared with normal subjects and other populations. Human genomic DNA was isolated. Genotyping was performed by Polymerase chain reaction followed by restriction endonucleases digestion for variants analysis. The results indicated gene frequency of CYP2D6*1 was 59% (CI 49.6,68.3%) in normal subjects whereas, CYP2D6*4 was 13% (CI 3.7, 22.3%) and CYP2D6*10 was 54% (44.7, 63.3%) predominantly found in depressed patients. The results demonstrate pronounced association of CYP2D6 *4 and *10 allelic variants with patient’s drug response activity.


1972 ◽  
Vol 120 (555) ◽  
pp. 173-182 ◽  
Author(s):  
R. W. Payne ◽  
D. V. Hawks ◽  
D. Friedlander ◽  
D. S. Hart

Cameron (1938, 1939) suggested that schizophrenic thought disorder is largely the result of overinclusive thinking, which he defined as the inability to preserve conceptual boundaries. Payne, Matussek and George (1959) developed a battery of objective measures of overinclusive thinking, which they found differentiated between an acute schizophrenic and a neurotic control group. Payne and Hewlett (1960) found that a battery of tests of overinclusive thinking intercorrelated as expected. They were able to obtain a factor score from their overinclusion test battery which differentiated a group of acute schizophrenic patients from control groups of depressives, neurotics and normal subjects. Payne and Friedlander (1962), on the basis of this factorial study, suggested a short battery of three measures of overinclusive thinking consisting of the number of ‘Non-A’ or unusual responses to the Object Classification Test (Payne, 1962), the average number of words used in explaining the Benjamin Proverbs given under special 'stress free’ instructions, and the average number of objects classified together in the ‘handing over’ section of the Goldstein-Scheerer Object Sorting Test. This standard test battery has been the operational definition of overinclusive thinking in a number of studies. Only one study of the reliability of this test battery appears to have been carried out. Hawks and Payne (1971) report the correlations obtained from a group of 54 psychiatric inpatients who were retested after a 4-day interval. The test-retest correlation coefficient (uncorrected) obtained from the Combined Transformed score (Payne and Friedlander, 1962) was 0 · 87. The reliabilities of the individual tests ranged from 0·77 to 0·86.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1486-1486
Author(s):  
F. Ranjbar ◽  
M. Sabagh Razavi ◽  
M.A. Ghorayshizadeh ◽  
J. Shokri ◽  
M. Asadlo

IntroductionConsidering the shortcomings of antipsychotics in treatment of negative symptoms of schizophrenic patients, the use of augmentation treatment for decreasing the negative symptoms is highly important.AimsThe aim of this research was to study the effect of selegiline augmentation with antipsychotic drugs in decreasing the negative symptoms of schizophrenic patients.MethodsIn this double blind randomized control trial study 70 schizophrenic in- patients who were under treatment with antipsychotics were randomly divided into two intervention and control groups. The patients of both groups were given placebo for two weeks along with antipsychotics. For 12 weeks the intervention group was given selegiline 10 mg/day and control group was given placebo. The patients were evaluated with PANSS scale and Hamilton depression test at the end of first and second weeks and then at the end of every other week for twelve weeks. Then the results were analyzed statistically.ResultsThere was no significant difference between intervention and control groups considering PANSS score on first and second weeks, but the difference on 4-14 weeks was statistically significant. There was also no statistically significant difference in Hamilton depression Test between the two groups in first to 10 Th weeks. But the difference was statistically significant in 12–14 weeks.ConclusionsAugmentation treatment with selegiline can improve the negative symptoms of schizophrenic patients.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
A. Homayouni ◽  
G.A. Nikpour ◽  
A. Khanmohammadi ◽  
S.J. Mosavi Amiri

Introduction and aim:Based on clinical observations individuals with schizophrenia have deficits in a large number of functional domains, including social skills, social cognition, difficulties in perceiving, understanding, anticipating and reacting to social cues and deficient in social networks that are crucial for normal social interaction. (Yager and Ehmann, 2006). Disturbances and disorders in the domains are thought to explain impairments in social functioning that potentially have an direct link to social behavior, social function and interaction with others. in this field and for better and more understanding about schizophrenia, the study aims to investigate reaction time to stimuli in the field of light and sound attention and perception in schizophrenic patients and comparison with normal people.Method:Method of the research is experimental. 30 schizophrenic subjects were randomly selected from three psychiatric hospitals and compared with 30 normal subjects. Chronoscope apparatus was used to assess reaction time to light and sound stimuli. the apparatus assesses the light and sound stimuli in 0/001 seconds. Independent T test was used to analyze and compare means of experiment group (schizophrenic subjects) with control group (normal subjects).Results:Analysis of means showed differences between groups. Normal subjects were much more rapid in reaction and responding to light and sound than schizophrenic subjects.Conclusion:Findings showed schizophrenic subjects because of their affective and emotional disorders and depressed temperament that caused to disorder in abilities and functions, cannot response rapid to light and sound than normal people.


Author(s):  
Tamkeen Fatima

CYP2D6 gene polymorphism is considered a main obstacle in the process of drug metabolism under clinical diseases that affect pharmacokinetics of ~25% of antidepressants and other drugs. Inter-individual variation occurs in the amount and functional activity of CYP2D6 enzyme produce undesirable side effects. The primary aim of current research is to evaluate gene and genotypic frequencies of CYP2D6 *1 extensive metabolizer, *4 poor metabolizer and *10 intermediate metabolizer allelic variants among depressed patients and compared with normal subjects and other populations. Human genomic DNA was isolated. Genotyping was performed by Polymerase chain reaction followed by restriction endonucleases digestion for variants analysis. The results indicated gene frequency of CYP2D6*1 was 59% (CI 49.6,68.3%) in normal subjects whereas, CYP2D6*4 was 13% (CI 3.7, 22.3%) and CYP2D6*10 was 54% (44.7, 63.3%) predominantly found in depressed patients. The results demonstrate pronounced association of CYP2D6 *4 and *10 allelic variants with patient’s drug response activity.


1988 ◽  
Vol 153 (5) ◽  
pp. 667-674 ◽  
Author(s):  
Geoffrey N. Smith ◽  
William G. Iacono ◽  
Margaret Moreau ◽  
Karen Tallman ◽  
Morton Beiser ◽  
...  

The literature indicates that whether or not schizophrenic patients are reported to have significant lateral ventricular enlargement depends on control, and not schizophrenic-group values. This discrepancy does not result from differences in age, the ratio of males to females, the number of control subjects used in each study, or whether control groups are comprised of normal subjects or medical patients. However, medical-patient controls tend to have smaller ventricles than do normal individuals. Thus, we assessed lateral-and third-ventricle size and the degree of cortical atrophy in 30 normal volunteers, 30 medical patients, and 30 chronic schizophrenic patients. The use of a medical control group seemed to result in underestimates of ventricle and sulcal size in the normal population and, therefore, overestimates of these values in schizophrenic groups.


1982 ◽  
Vol 78 (4) ◽  
pp. 342-345 ◽  
Author(s):  
John Metz ◽  
Henry H. Holcomb ◽  
Herbert Y. Meltzer

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