1.Life event,stress and illness
Malaysian Journal of Medical Sciences 2008;15(4):9-18
The relationship between stress and illness is complex. The susceptibility to stress varies from person to person. Among the factors that influenced the susceptibility
to stress are genetic vulnerability, coping style, type of personality and social support. Not all stress has negative effect. Studies have shown that short-term
stress boosted the immune system, but chronic stress has a significant effect on the immune system that ultimately manifest an illness. It raises catecholamine and
suppressor T cells levels, which suppress the immune system. This suppression, in turn raises the risk of viral infection. Stress also leads to the release of histamine,
which can trigger severe broncho-constriction in asthmatics. Stress increases the risk for diabetes mellitus, especially in overweight individuals, since psychological stress alters insulin needs. Stress also alters the acid concentration in the stomach,
which can lead to peptic ulcers, stress ulcers or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries (atherosclerosis), especially if
combined with a high-fat diet and sedentary living. The correlation between stressful life events and psychiatric illness is stronger than the correlation with
medical or physical illness. The relationship of stress with psychiatric illness is strongest in neuroses, which is followed by depression and schizophrenia. There is
no scientific evidence of a direct cause-and-effect relationship between the immune system changes and the development of cancer. However, recent studies found a
link between stress, tumour development and suppression of natural killer (NK) cells, which is actively involved in preventing metastasis and destroying small metastases.
2.Influence of CYP2D6 polymorphisms on symptomatology and side effects of patients with schizophrenia in Malaysia
Zalina Zahari ; Mohd Razali Salleh ; Lay Kek Teh ; Rusli Ismail
Malaysian Journal of Medical Sciences 2009;16(3):13-22
Background: Our objective was to investigate the association of CYP2D6 polymorphisms with
symptoms and side-effects of patients with schizophrenia.
Methods: The subjects were 156 patients with schizophrenia undergoing antipsychotic treatment
at a psychiatric clinic. Patients with co-morbid diagnoses of substance abuse or mental retardation were
excluded from the study. Psychopathology was evaluated using the Positive and Negative Symptoms
Scale (PANSS). Extrapyramidal side-effects and akathisia were assessed with the Simpson Angus Scale
(SAS) and the Barnes Akathisia Rating Scale (BARS), respectively. DNA was extracted from blood and
subjected to PCR-genotyping.
Results: We found that CYP2D6 polymorphisms were significantly associated with a subtotal
negative PANSS score. In addition, CYP2D6 is not related to side-effects of antipsychotic therapy, or
SAS and BARS scores. The results suggest that CYP2D6 polymorphisms may have implications in
treatment response.
Conclusions: Therefore, CYP2D6 may be a predictor for treatment outcomes of patients with
schizophrenia. However, further investigation is required to confirm these findings in a larger sample.
3.A Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for the Detection of DRD2 Polymorphisms
Zalina Zahari ; Mohd Razali Salleh ; Mohd Khairi Zahri @ Johari ; Nurfadhlina Musa ; Rusli Ismail
Malaysian Journal of Medical Sciences 2011;18(4):44-57
Background: The dopamine D2 receptor gene (DRD2) plays a role in many diseases such as schizophrenia, Parkinson’s disease, and addictive behaviour. Methods currently available for the detection of DRD2 polymorphisms are costly and cannot detect all 8 polymorphisms of our research interest simultaneously (Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, A-241G, and −141C Ins/Del). Therefore, we developed a nested multiplex polymerase chain reaction (PCR) for simultaneous detection of these polymorphisms.
Methods: Genomic DNA was extracted from blood using standardised methods. Primers specific at the 3’-end for the polymorphic sites were designed. A two-step PCR method was developed. In the first PCR, a region from exon 3 to 4, exon 7, the promoter region, and the 3’-region of DRD2 were specifically amplified. The products were subsequently used as templates in the second PCR. Sequencing was performed to validate the test results.
Results: Specific bands corresponding to the amplified product of interest were obtained. The method was reproducible and specific when used to genotype patients with schizophrenia. The amplified sequences showed 100% homology to the DRD2 sequence.
Conclusion: The method was found to be simple, rapid, specific, and reproducible for the simultaneous detection of the DRD2 polymorphisms.