| Introduction:Post-stroke depression (post-stroke depression, PSD) refers to depression after stroke, interest waned as the main manifestations of disease, the clinical features, including depression, anxiety, diminished interest, sleep disturbance, early awakening, and weight loss. The prevalence of PSD accounted for 25% to 79% with stroke patients. PSD have a significant influence to the neurological deficit and recovery of cognitive impairment in stroke patients, and PSD is a potential risk factor to increase the post-stroke mortality and suicide rate. PSD impacts the quality of life in stroke patients for a long time, and people take more attention to PSD.The pathogenesis of PSD is not entirely clear yet. There are three mechanisms mainly. (1) From the neuroanatomical mechanisms, there are studies that the local blood hypoperfusion in the left frontal and double-temporal lobe relate to the occurrence of PSD. (2) From the social psychology mechanism, some scholars believe that family of stroke patients and social support, economic status, motor function, changes of the capacity in participating in family and community activity, and changes of the capacity in employment can lead to psychological imbalance in patients, finally lead to depression. (3) From the perspective of biological mechanisms, the occurrence of PSD related to the changes in neurobiology after brain damage:Because the neurons of norepinephrine and 5-HT locate in the brainstem, and their axons go through the hypothalamus, basal ganglia, around the corpus callosum and corona radiata, and finally to the frontal cortex.5-HT and noradrenergic neural pathways can be affected when the above regions are involve in, the norepinephrine and 5-HT decline,and then it leads to PSD. Numerous studies show that the incidence of PSD concerns with the 5-HT system. In recent years some scholars have used positron emission scanning (PET) in patients with cerebral metabolism in stroke research, studies have shown that the levels of NA and 5-HT neurotransmitters decline in patient's brain with PSD, and also found that levels of monoamine neurotransmitters in cerebrospinal fluid and degree of depression are negative correlation. Clinical application of selective 5-HT reuptake inhibitor (SSRI) and tricyclic antidepressants (TCA) can be effective in treating PSD, the mechanism is to promote the concentration of biogenic amines back to normal after stroke.5-HT receptors are many and complex,5-HT 2A receptor (Serotonin-2A receptor,5-HT2AR) is G protein-coupled receptor which is associated with phospholipase.5-HT2AR locates in the rear of synapses, and it mainly distributes in the nucleus, olfactory tubercle, hippocampus, frontal cortex and entorhinal cortex in the central nervous band system, other pear-shaped area in the liver, spleen and other peripheral tissues of species.5-HT2AR is inhibitory receptor, it can reduce the excitability of neurons when it is activated.5-HT2AR is closely related to a variety of mental activities in human, and it participates in a variety of mechanisms of psychotropic drugs, so 5-HT2AR is an important genetic markers in the study of mental illness. The genes of human 5-HT2AR locate on long arm of chromosome No. 13 14-21 District (13 q 14-21). Currently there are total of 5-HT2AR 5 polymorphism: two resting kinds including T 102 C polymorphism and the C 516 T, and 3 structural polymorphism kinds including Thr25 Asn, His 452 Thr and Ala 447 Val. Polymorphism of T 102 C, Thr 25 Asn are located in the first exon of the first part. T (-102) C polymorphism is in the non-coding regions, it cannot change the amino acid sequences, but it is in the same linkage disequilibrium region with other polymorphisms. In the site of 5-HT2AR T102C, if T allele saltat to C allele, the mutation can reduce the expression of 5-HT2AR, make 5-HT2AR binding decreased,5-HT2A receptor activation reduced, thereby increase the excitability of neurons.Study found that the sensitivity of 5-HT2A receptor is indicators of severe state of depression, and changes of central 5-HT2A receptor's binding may play an important role in the development of depression. Autopsy of patients with depression found in the cerebral cortex size of 5-HT2A receptor binding increased, and studies have shown that the 5-HT2A receptor's binding of peripheral platelet was higher in depression patients than in the normal control group.A large number of studies have shown that antidepressants can reduce the density of central 5-HT2AR in PSD patients, reduce postsynaptic 5-HT2A receptor, and reduce 5-HT2A receptor's affinity for 5-HT, finally the depressive symptoms improved. Meanwhile, some scholars have found that 5-HT2AR T102C gene polymorphism may be associated with the pathogenesis of depression, and C102 allele may be the protective factor for depression in male patients.In summary,5-HT content in the blood of PSD patients is related to the disease severity, it can be used as the indicator of reflecting the depression severity in PSD patients, while 5-HT 2A receptor T102C gene polymorphism is related to depression. Therefore, basing on the above two points, we though 5-HT2A receptor gene polymorphism may be associated with the genetic predisposition in PSD. The study in the relationship between 5-HT2A receptor gene polymorphism and PSD has not been reported in Home and abroad.Purpose:This study aimed to explore the relationship between the polymorphism of 5-HT 2A receptor T102C gene and post-stroke depression, to prove the genetic disease mechanism of post-stroke depression, and to provide molecular targets for the clinical diagnosis of PSD.Methods:To adopt a case-control study, to accord with the criteria of enrolled in and exclusion strictly, and to select 169 cases with post-stroke depression (PSD group) and patients without depression after stroke (simple stroke group), including post-stroke depression (PSD) 97 cases for the study group, while patients without depression after stroke (simple stroke group)72 cases for the control group. All subjects were drawn whole blood 2ml, EDTA anticoagulant to phenol-chloroform extraction of genomic DNA. The polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) techniques were applied to amplificate 5-HT 2A receptor T102C allele, the primers are upstream 5'-TCT GCT ACA AGT TCT GGC TT-3 'and downstream 5'-CTG CAG CTT TTT CTC TAG GG-3'. Mspl enzyme is applicated to test Tâ†'C polymorphism. Statistical package using SPSS 13.0, using chi-square test to compare the various genotypes and allele frequencies if be different between patients with PSD and patients without depression after stroke.Results:It was not statistically significant in the group differences of gender composition between simple stroke group and PSD group (t=-0.873, P=0.350). It was not statistically significant in the group differences of age distribution between simple stroke group and PSD group (X2=-1.263, P=0.208).The relationship between 5-HT2AR T102C gene polymorphism and PSD 5-HT2AR T102C gene polymorphism test results show that the frequencies of wild T allele and mutant C allele were 41.0%(59/144) and 59.0%(85/144) in simple stroke group; the frequencies were 56.7%(110/194) and 43.3%(84/194) in PSD group. The difference was statistically significant(X2=8.179, P<0.05, OR= 1.887,95% CI=1.219-2.921). The frequency of mutant C allele is lower in post-stroke depression group (43.3%) than in simple stroke group(59.0%),The distribution of various 5-HT2AR gene T102C genotypes:the genotype frequencies of wild homozygote Al/Al, heterozygous A1/A2, mutant homozygote A2/A2 were 16.7%(12/72),48.6%(35/72) and 34.7%(25/72) in simple stroke group; the genotype frequencies were 34.0%(33/97),45.4%(44/97),20.6%(20/97) in PSD group. It was statistically significant in the group differences of distribution of genotype frequencies between simple stroke group and PSD group (χ2=7.855, P <0.05).Conclusion:It was statistically significant in distribution of 5-HT 2A receptor T102C gene frequencies and genotype between simple stroke group and PSD group, suggesting that 5-HT 2A receptor T102C polymorphism may be associated with the pathogenesis of post-stroke depression,5-HT 2A receptor gene T102C may be the susceptibility gene on PSD, C allele may be the protective factor to whom suffering from PSD. |
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