الفهرس 
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Abstract
Major Depressive Disorder (MDD) is defined as a medical condition lasting for at least two weeks, where there is depressive mood or reduced interest/pleasure, accompanied by cognitive changes that significantly affect the individual’s capacity to function. Depressive disorders are likely to cause more disabilities than many other chronic diseases. It was considered to be the second leading cause of disability worldwide in the year 2010. It was estimated to be the most common mental disorder in Egypt with a prevalence of 2.7%. One of the systems controlling the mood is the endocannabinoid system. It is widely distributed throughout neural regions known to be integral for the regulation of mood and emotion. At the signaling level, the cannabinoid CB1 receptor has been implicated in the etiology of depression. Deficiencies in CB1 receptor signaling or blocking the endocannabinoid receptors may cause MDD. The CB1 receptor is encoded by the gene CNR1. The endocannabinoid system is regulated by antidepressant treatment regimens. Treatment of MDD can be achieved by using the selective Serotonin Reuptake Inhibitors (SSRIs) which were found to be associated with the antidepressant effects of the endocannabinoid system. Two polymorphisms: the SNPs 4895 A/G (rs806368) and 1359 G/A (rs1049353) are associated with increased risk of MDD and response to antidepressant treatment regimen.
The aim of this work was to study the impact of polymorphisms 4895 A/G (rs806368) and 1359 G/A (rs1049353) in CNR1 gene on the susceptibility to develop major depressive disorder and to investigate their role as predictors of treatment response to the antidepressant drug Escitalopram.
The study involved fifty adult cases of Major Depressive Disorder, and fifty healthy subjects without history of psychiatric disorders as control group.
Methods:
1- All patients were subjected to a questionnaire to assess the socio-demographics: age, gender, parental consanguinity and family history.
2- Diagnosis of patients using Mini International Neuropsychiatric Interview (MINI-plus) to diagnose major depressive disorder and exclude other psychiatric illnesses.
3- Determination of the base-line severity of MD using Hamilton Rating Scale of Depression (HRSD).
4- Treatment of patients using Escitalopram with a dose 20 mg/day for six weeks. Depression severity was determined with HRSD after 2 weeks of treatment for follow-up and after 6 weeks of treatment to determine the drug response.
5- Response and no response to treatment were determined by comparing the baseline score of HRSD with the score after 6 weeks of treatment.
6- Molecular study:
It was applied on the fifty patients and the fifty healthy controls, as follows:-
a) DNA extraction by a modified salting-out technique.
b) PCR reaction for both polymorphisms using specific pair of primers for each polymorphism.
Summary
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c) RFLP method using a specific restriction enzyme for each polymorphism.
Results:
34.2% of patients with severe MDD, and 58.3% of patients with moderate MDD; were found in the age group of 28-37 years.
Gender difference had no effect on the severity of MDD.
30% of total patients had positive parental consanguinity, while 34% of them had positive family history of MDD.
81.6% of patients with severe MDD; and 100% of patients with moderate MDD responded to treatment.
In severe MDD, 52.6% were male responders while 29% were female responders. In moderate MDD, 58.3% were male responders and 41.7% were female responders.
Molecular study results:
The polymorphism rs806368 (4895 A/G):
- The polymorphism rs806368 (4895 A/G) had no effect on the occurrence of MDD. Same result was obtained when patients and controls were stratified by gender.
- The genotypes AG and GG were significantly higher in responders than non-responders to treatment.
- The frequency of genotypes AG and GG were significantly higher in male responders than in male non-responders in the total patients group and the severe MDD patients group.
The polymorphism rs1049353 (1359 G/A):
- This polymorphism neither had an impact on the susceptibility to develop MDD nor an effect on treatment response.
Allele frequencies of both polymorphisms were in Hardy-Weinberg equilibrium.
The polymorphisms 4895 A/G (rs806368) and 1359G/A (rs1049353) together:
- The frequency of the combination of genotypes AG + G’A’ of polymorphisms 4895 A/G (rs806368) and 1359G/A (rs1049353) respectively, was found more among patients.