Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.

Lower limb muscle strength and serotonin receptor gene polymorphism as factors associated in women with fibromyalgia

Abstract Background: Fibromyalgia (FM) is a chronic pain syndrome characterized by generalized skeletal muscle chronic pain. Its etiology is not well defined, because there are several factors that may trigger it such as physical and/or emotional stresses, or a genetic susceptibility, involving serotonergic, dopaminergic and catecholaminergic paths. The objective of this study was to investigate the association between the strength of the lower limb, genetic polymorphism of the serotonin receptor gene HTR2a in women with fibromyalgia. Methods: In this observational study of case-control type 48 women were evaluated who belonged to the group with FM (52 ± 12 years) and 100 women in the control group (58±11 years). Socio demographic and anthropometric data were collected and peripheral blood samples for DNA extraction; genotypic analyzes were performed by means of PCR in real time by TaqMan® system. The lower limb muscle strength was assessed through the test of sitting down and standing up for 30 s. The chi-square test or Fischer Exact was used for possible associations among the variables; the t-test for independent samples was used to compare the averages among the groups; the value of significance adopted was 5%. Results: There was an association between the polymorphism of the HTR2A gene with FM, demonstrating that carriers of the genotype GG have 24.39 times more likely to develop the syndrome (IC95% 5.15-115.47; p = 0.01). It was observed an association between FM and the test to sit and stand up demonstrating that women with fibromyalgia have lower limb muscle strength ( p = 0.01). The study showed that the white race has 3.84 times more likely to develop FM (p = 0.01). Conclusion: The results of this study suggest that women of Caucasian ethnicity with GG genotype or G allele presented greater risk of developing fibromyalgia and that these patients have lower limb muscle strength compared to the control group.

Antipsychotics for patients with pain

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D₂ receptor bindings with strong binding to the 5-HT(2A) receptor, while typical antipsychotics block long-lasting, tight D₂ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine (10~100 µM) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine (30 µM), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-HT(2A) receptor inhibitor, indicating that ketamine facilitated the activation of 5-HT(2A) receptors. Anpirtoline and BW723C86, selective agonists of 5-HT(1B) and 5-HT(2B) receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-HT(2A) receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-HT(2A) receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.

Associations between Serotonergic Genes and Escitalopram Treatment Responses in Patients with Depressive Disorder and Acute Coronary Syndrome: The EsDEPACS Study

Genes related to serotonin are associated with responses to treatment for depression. We examined associations between the serotonin transporter (5-HTT) and serotonin 2a receptor (5-HTR2a) genes and responses to treatment for depressive disorders in acute coronary syndrome (ACS). A total of 255 patients who met the DSM-IV major or minor depressive disorder and recently developed ACS were randomly assigned to the escitalopram (n=127) or placebo (n=128) group in this 24-week double-blind trial (ClinicalTrial.gov identifier: NCT00419471). Remission was defined as a Hamilton Rating Scale for Depression (HAMD) score < or =7. Assays were performed for the 5-HTTLPR, STin2 VNTR, 5-HTR2a 102T/C, and 5-HTR2a 1438A/G genotypes. Escitalopram was superior to placebo for treating depressive disorder with ACS but there were no significant associations between serotonergic genes and treatment responses even when considering ACS severity. The effect of escitalopram was independent of 5-HTT and 5-HTR2a polymorphisms.

Effects of blockade of 5-HT2A receptors in inflammatory site on complete Freund's adjuvant-induced chronic hyperalgesia and neuropeptide Y expression in the spinal dorsal horn in rats / 生理学报

5-hydroxytryptamine (5-HT) released in inflammatory tissues plays a pivotal role in pain hypersensitivity. However, it is not clear whether 5-HT2A receptors in the inflamed tissues mediate this effect. The present study investigated the contribution of 5-HT2A receptors in the periphery to chronic inflammatory pain. Complete Freund's adjuvant (CFA) was injected subcutaneously in the hindpaw of rats. The selective 5-HT2A receptor antagonist ketanserin was given in the inflamed site. Paw withdrawal latency responding to heat or mechanical stimuli was measured. Expression of neuropeptide Y (NPY) in the spinal dorsal horn and dorsal root ganglia (DRG) was assayed using immunohistochemistry technique. The results showed that ketanserin administered in the inflamed site inhibited thermal hyperalgesia in a dose-dependent manner (20, 40 and 80 µg) induced by the intraplantar injection of CFA. Ketanserin given once per day at a dose of 80 µg abolished heat hyperalgesia and also attenuated mechanical allodynia on the third day. CFA injection increased the expression of NPY in superficial laminae of the spinal cord, but not in the DRG. The local treatment of ketanserin completely inhibited CFA-induced increase in NPY expression in superficial laminae of the spinal cord. These results indicated that activation of 5-HT2A receptors in the inflamed tissues was involved in the pathogenesis of inflammatory pain and the blockade of 5-HT2A receptors in the periphery could relieve pain hypersensitivity and normalize the cellular disorder in the spinal dorsal horn associated with pathological pain. The present study suggests that the peripheral 5-HT2A receptors can be a promising target for pharmaceutical therapy to treat chronic inflammatory pain without central nervous system side effects.

Changes of Serotonin (5-HT), 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression, Myocardial Infarction and Myocardial Infarction Co-exist with Depression / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>To evaluate whether serotonin (5-HT), 5-HT2A receptor (5-HT2AR), and 5-HT transporter (serotonin transporter [SERT]) are associated with different disease states of depression, myocardial infarction (MI) and MI co-exist with depression in Sprague-Dawley rats.</p><p><b>METHODS</b>After established the animal model of four groups include control, depression, MI and MI with depression, we measured 5-HT, 5-HT2AR and SERT from serum and platelet lysate.</p><p><b>RESULTS</b>The serum concentration of 5-HT in depression rats decreased significantly compared with the control group (303.25 ± 9.99 vs. 352.98 ± 13.73; P = 0.000), while that in MI group increased (381.78 ± 14.17 vs. 352.98 ± 13.73; P = 0.000). However, the depression + MI group had no change compared with control group (360.62 ± 11.40 vs. 352.98 ± 13.73; P = 0.036). The changes of the platelet concentration of 5-HT in the depression, MI, and depression + MI group were different from that of serum. The levels of 5-HT in above three groups were lower than that in the control group (380.40 ± 17.90, 387.75 ± 22.28, 246.40 ± 18.99 vs. 500.29 ± 20.91; P = 0.000). The platelet lysate concentration of 5-HT2AR increased in depression group, MI group, and depression + MI group compared with the control group (370.75 ± 14.75, 393.47 ± 15.73, 446.66 ± 18.86 vs. 273.66 ± 16.90; P = 0.000). The serum and platelet concentration of SERT in the depression group, MI group and depression + MI group were all increased compared with the control group (527.51 ± 28.32, 602.02 ± 23.32, 734.76 ± 29.59 vs. 490.56 ± 16.90; P = 0.047, P = 0.000, P = 0.000 in each and 906.38 ± 51.84, 897.33 ± 60.34, 1030.17 ± 58.73 vs. 708.62 ± 51.15; P = 0.000 in each).</p><p><b>CONCLUSIONS</b>The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression. Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.</p>

5-Hydroxytryptamine (serotonin) 2A receptor gene polymorphism is associated with schizophrenia.

Background & objectives: Schizophrenia, the debilitating neuropsychiatric disorder, is known to be heritable, involving complex genetic mechanisms. Several chromosomal regions associated with schizophrenia have been identified during the past; putative gene (s) in question, to be called the global signature for the pathophysiology of the disease, however, seems to evade us. The results obtained from the several population-wise association-non association studies have been diverse. we therefore, undertook the present study on Tamil speaking population in south India to examine the association between the single nucleotide polymorphisms (SNPs) at the serotonin receptor gene (5HT2A) and the occurrence of the disease. Methods: Blood samples collected from 266 cases and 272 controls were subjected to genotyping (PCR amplification of candidate SNPs, RFLP and sequencing). The data on the SNPs were subjected to statistical analysis for assessing the gene frequencies in both the cases and the controls. Results: The study revealed significant association between the genotypic frequencies of the serotonin receptor polymorphism and schizophrenia. SNP analysis revealed that the frequencies of GG (30%, rs6311) and CC genotypes (32%, rs6313), were higher in patients (P<0.05) than in controls. The study also showed presence of G and C alleles in patients. significant levels of linkage disequilibrium (LD) were found to exist between the genotype frequencies of rs6311 and rs6313. Interpretation & conclusions: This study indicated an association between the SNPs (rs6311 and rs6313) of the serotonin receptor 5HT2A and schizophrenia. HapMap analysis revealed that in its genotype distribution, the Tamil speaking population was different from several other populations across the world, signifying the importance of such ethnicity-based studies to improve our understanding of this complex disease.

Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase

Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K+ (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca2+-activated K+, inward rectifier K+ and ATP-sensitive K+ channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca2+ channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, alpha-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.

No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

OBJECTIVE: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. METHODS: One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). RESULTS: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. CONCLUSION: Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.

A Case of Blonanserin-Induced Mania in Schizophrenia / 대한정신분열병학회지

Schizophrenia is a psychiatric disease which requires a long term treatment. Thus, patient's therapeutic compliance can be very crucial to the disease's prognosis. Moreover, the adverse effects of drugs are also important to determine the patient's therapeutic compliance. The atypical antipsychotic drugs have been improved in the way to strengthen therapeutic effects and to reduce adverse effects. Blonanserin, an atypical antipsychotic, is a selective serotonin-dopamine agonist which blocks the dopamine D2/D3 receptors and serotonin 5-HT2A receptor. Blonanserin is well known to include parkinsonism, akathisia and insomnia. In this case report, Blonanserin treatment was given to patients who admitted to the closed ward due to psychotic symptoms such as idea of reference, persecutory delusion, auditory hallucination and blunted affect. The patients showed manic symptoms including elated mood, talkativeness, hyperactivity after the increase of Blonanserin dose up to 24 mg. Such manic symptoms were improved after Blonanserin dose was decreased to 16 mg. Many researches have reported newly-evoked manic/hypomanic episodes in schizophrenic patients after the use of atypical antipsychotics such as Risperidone, Olanzapine and Ziprasidone. However, there is no report of Blonanserin-induced manic/hypomanic episode. Therefore, further study is necessary to evaluate the manic/hypomanic episodes which are thought to be the adverse effects of Blonanserin.

A Case of Blonanserin-Induced Mania in Schizophrenia / 대한정신분열병학회지

Schizophrenia is a psychiatric disease which requires a long term treatment. Thus, patient's therapeutic compliance can be very crucial to the disease's prognosis. Moreover, the adverse effects of drugs are also important to determine the patient's therapeutic compliance. The atypical antipsychotic drugs have been improved in the way to strengthen therapeutic effects and to reduce adverse effects. Blonanserin, an atypical antipsychotic, is a selective serotonin-dopamine agonist which blocks the dopamine D2/D3 receptors and serotonin 5-HT2A receptor. Blonanserin is well known to include parkinsonism, akathisia and insomnia. In this case report, Blonanserin treatment was given to patients who admitted to the closed ward due to psychotic symptoms such as idea of reference, persecutory delusion, auditory hallucination and blunted affect. The patients showed manic symptoms including elated mood, talkativeness, hyperactivity after the increase of Blonanserin dose up to 24 mg. Such manic symptoms were improved after Blonanserin dose was decreased to 16 mg. Many researches have reported newly-evoked manic/hypomanic episodes in schizophrenic patients after the use of atypical antipsychotics such as Risperidone, Olanzapine and Ziprasidone. However, there is no report of Blonanserin-induced manic/hypomanic episode. Therefore, further study is necessary to evaluate the manic/hypomanic episodes which are thought to be the adverse effects of Blonanserin.

Serotonin 2A Receptor Gene Polymorphism in Korean Children with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: The purpose of this study was to investigate the association between the T102C polymorphism in the serotonin 2A receptor gene and attention-deficit/hyperactivity disorder (ADHD) in Korean patients. METHODS: A total of 189 Korean children with ADHD as well as both parents of the ADHD children and 150 normal children participated in this study. DNA was extracted from blood samples from all of the subjects, and genotyping was conducted. Based on the allele and genotype information obtained, case-control analyses were performed to compare the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were used for family-based association testing (number of trios=113). Finally, according to the significant finding which was showed in the case-control analyses, the results of behavioral characterastics and neuropsychological test were compared between ADHD children with and without the C allele. RESULTS: In the case-control analyses, statistically significant differences were detected in the frequencies of genotypes containing the C allele (chi2=4.73, p=0.030). In the family-based association study, TDTs failed to detect linkage disequilibrium of the T102C polymorphism associated with ADHD children. In the ADHD children, both the mean reaction time and the standard deviation of the reaction time in the auditory continuous performance test were longer in the group with the C allele compared to the group without the C allele. CONCLUSION: The results of this study suggest that there is a significant genetic association between the T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.

Blonanserin: New Serotonin-Dopamine Antagonist / 대한정신약물학회지

Blonanserin is a newly developed agent which is approved for the treatment of schizophrenia in Japan and Korea. This agent has high affinity to dopamine D2 receptor and serotonin 5-HT2A receptor. Blonanserin was as effective as risperidone in the treatment of schizophrenia, and showed greater efficacy in negative symptoms than haloperidol. Blonanserin was well tolerated in both the short- and long-term studies, and the frequency and intensity of EPS is generally similar with risperidone. For other side effects, blonanserine seems to have better safety profiles compared with other atypicals, and showed less prolactin elevation than risperidone. These findings suggest that blonanserin is useful in the treatment of schizophrenia.

Tardive Dyskinesia: Treatment with Aripiprazole

Tardive dyskinesia is characterized by choreiform movements, or rhythmic abnormal involuntary movements of the face, mouth, tongue, trunk, and limbs. It is frequently associated with the use of neuroleptic medications. The choreiform movements are irreversible in some patients, even after the drug is withdrawn. Although no reliable treatment for tardive dyskinesia exists, atypical antipsychotics are associated with a significantly lower incidence of tardive dyskinesia than typical antipsychotics. Moreover, recent reports suggest that atypical antipsychotics may have a beneficial effect on tardive dyskinesia remission. Until recently, evidence for the effectiveness of aripiprazole on tardive dyskinesia has been mixed. Aripiprazole has a unique mechanism of action and has various effects in tardive dyskinesia. The drug acts as a partial D2 receptor agonist that can stabilize D2 up-regulation, and as a partial 5-HT1A receptor agonist and a 5-HT2A receptor antagonist, and can increase the release of dopamine in the striatum.

[Effect of melatonin on sexual behavior in male diabetic rats]

Several clinical studies indicate deterioration of sexual behavior in diabetic patients. The pathophysiological mechanisms of diabetic sexual impotence remain obscure. In this study the therapeutic effects of melatonin on sexual behavior were investigated through the central serotonergic system in diabetic rats. In this study, 30 male adult Wistar rats, weighing 200 +/- 20 g, were used. Animals were divided into three groups, the controls [C], diabetic [D] and the melatonin-treated diabetic [M] group. Experimental diabetes was induced by intraperitoneal injection of 50 mg/kg streptozotocin. Melatonin was injected [10 mg/kg i. p.] after 3 days of streptozotocin injection for 30 days. At the end of the administration period, the sexual behavior of each male rat to an ovariectomized female rat was assessed for 40 min. Serotonergic type 2 [5-HT2A] receptor activities were investigated through spontaneous WDS behavior, and experimental data were statistically analyzed. First mount, first intromission and first ejaculation latencies significantly [p<0. 05] increased in diabetic rats as compared to controls. Melatonin treatment significantly [p<0. 05] reduced these responses in the M group, compared to the D one. Also the number of mounts, intromissions and ejaculations significantly [p<0. 05] decreased in diabetic rats compared to controls. Administration of melatonin significantly [p<0. 05] increased these activities in the M group as compared to the D one. Calculation of copulatory efficiency and the sexual activity index of each rat indicate that reproductive activity in diabetic rats was significantly [p<0. 05] less than other two groups. The number of WDS responses was significantly [p<0. 05] different in all three groups. Sexual dysfunction in diabetic animals was accompanied by decreasing of 5-HT2A receptor activities, and melatonin prevented the diabetes-induced sexual impotence by modulating of central serotonergic system activity

Comparative pharmacophore analysis of dual dopamine D2/5-HT(2A) receptor antagonists / 药学学报

Dual dopamine D2/5-HT2A receptor antagonists have potent activity and are referred to atypical antipsychotics due to their lower propensity to elicit EPS and their moderate efficacy toward negative symptoms. However, an on-going challenge in developing atypical antipsychotics drugs is to maintain the favorable profiles and avoid of cardiovascular risk. In this paper, comparative pharmacophore analysis of dual dopamine D2/5-HT2A receptor antagonists, hERG K+ channel blockers, and alA adrenoceptor antagonists is carried out, and the results could give some insight into multi-target drug design.

Genetic polymorphism of the PRODH and 5-HT(2A) receptor gene in Korean-Chinese and Han nationality in Chinese Yanbian area / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the polymorphisms distribution of genes related with mental diseases, such as proline dehydrogenase gene (PRODH) and serotonin 2A(5-HT(2A)) receptor gene, among Korean-Chinese and Han nationality in Chinese Yanbian area.</p><p><b>METHODS</b>By utilizing techniques of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the polymorphisms for -1945 region of the PRODH gene and -1438 region of the 5-HT(2A) receptor gene were analyzed.</p><p><b>RESULTS</b>The PRODH genotype frequencies of MM, Mm and mm in Korean-Chinese population were 61.4%,34.4%,4.2% respectively, the allele frequencies were 0.786 for M and 0.214 for m respectively, and those in Han population were 55.2%,38.5%,6.3%, 0.745 and 0.255 respectively. The 5-HT(2A) receptor gene genotype frequencies of AA, AG and GG in Korean-Chinese population were 15.6%,67.7%,16.7% respectively, the allele frequencies were 0.495 for A and 0.505 for G respectively, and those in Han population were 11.5%,65.6%,22.9%, 0.443 for A and 0.557 for G.</p><p><b>CONCLUSION</b>All of the genotype distribution of both loci in Chinese Korean and Han nationality in Yanbian area meet Hardy-Weinberg equilibrium, and show stronger ability in human identity. The data obtained can be used in human identity, paternity testing and Chinese Korean ethnic group study.</p>

Role of 5-HT(2A) receptor in increase in respiratory-related rhythmic discharge activity by nikethamide in neonatal rat transverse medullary slices / 生理学报

To investigate the effects of nikethamide on the generation and modulation of rhythmic respiration of neonatal rats and the role of 5-HT(2A) receptor in this course, experiments were performed on the transverse medullary slices of neonatal rats (both sexes, 1-3 d) in vitro. The slices containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared in which the respiratory-related rhythmic discharge activity (RRDA) was recorded from the hypoglossal nerve rootlets by suction electrode. The possible role of nikethamide on RRDA was investigated by administration of an agonist of 5-HT(2A) receptor, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and an antagonist of 5-HT(2A) receptor, ketanserine, dissolved in modified Krebos solution (MKS). Thirty slices were randomly divided into five groups: Group 1: the slices were perfused with different concentrations of nikethamide (0.5, 1, 3, 5, 7, 10 μg/mL), and the most effective concentration was selected; Group 2: the slices were perfused with DOI (40 μmol/L); Group 3: the slices were perfused with ketanserine (40 μmol/L); Group 4: the slices were perfused with ketanserine + DOI; Group 5: the slices were perfused with nikethamide, then perfused with nikethamide + ketanserine after washout of nikethamide. Nikethamide increased RRDA in transverse medullary slices at 0.5-7 μg/mL, and 5 μg/mL was the most effective concentration. DOI increased RRDA with prolonged inspiratory time (TI), increased integral amplitude (IA), and shortened respiratory cycle (RC). Ketanserine decreased RRDA with shortened TI, decreased IA and prolonged RC. Ketanserine + DOI had no significant effects on RRDA. The effects of nikethamide on RC and IA were totally and partially reversed by additional application of ketanserine, but the effect of nikethamide on TI was not influenced by ketanserine. It is proposed that nikethamide increases RRDA partly via 5-HT(2A) receptors.