• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.149-154
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• 2015

Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. Many prescribed antidepressants modulate monoamine neurotransmitters including serotonin, norepinephrine and dopamine. There has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of major depressive disorder (MDD). Recently, ketamine, an N-methyl-D-aspartate receptor antagonist, has received attention and has been investigated for clinical trials and neurobiological studies. In this article, we will review the clinical evidence for glutamatergic dysfunction in MDD, the progress with ketamine as a rapidly acting antidepressant, and other N-methyl-D-aspartate receptor antagonist for treatment-resistant depression.

• Korean Journal of Biological Psychiatry
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• v.14 no.3
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• pp.167-176
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• 2007

Objectives:A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to antipsychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes(DRD2, DRD3 and DRD4, respectively). Methods:We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia(DSM-IV) who were treated with various antipsychotics(94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4. Results:Among the total patients of 200, 141(70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders. Conclusion:These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polym- orphism in the DRD3, and the exon III 48bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.

• Anxiety and mood
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• v.4 no.2
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• pp.142-147
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• 2008

Objective : Evidence from recent studies supports the role of genetic factors in the development of Posttraumatic Stress Disorder (PTSD). The primary aim of this study is to investigate the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. The second aim is to examine the association between the DRD2 TaqI A polymorphism and clinical symptoms in patients with PTSD. Methods : We recruited 189 Vietnam veterans for participation in this study, among whom 99 were PTSD patients and 90 were control subjects. The presence of the DRD2 TaqI A polymorphism was determined by polymerase chain reaction (PCR). Several standardized research scales were used in the clinical assessment of PTSD, including the Combat Exposure Scale (CES), Clinician Administered PTSD Scale (CAPS), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI). Results : There was no significant difference in the distribution of the DRD2 genotype, frequency and prevalence of the A1 allele, or the frequency of heterozygotes between the patients with PTSD and the controls. In the PTSD group, the patients with the A1 allele (A1A1, A1A2) scored higher on the CAPS-total (p=0.044), CAPS-avoidance symptoms (p=0.016) and BDI (p=0.024) than those without the A1 allele (A2A2). Conclusion : We could not find an association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. However, the A1 allele of DRD2 seemsto influence avoidance symptoms in patients with PTSD.

• Korean Journal of Biological Psychiatry
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• v.13 no.4
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• pp.299-304
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• 2006

Objectives : The purpose of the present study was to investigate whether the TaqI A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. Methods : DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. Results : The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. Conclusion : No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.208-219
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• 2001

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.421-426
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• 1997

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[$^{18}F$]fluoromethylbenzyl)spiperone ([$^{18}F$]FMBS), a newly developed derivative of spiperone, as a potentially more selective radiotracer for the dopamine (DA) $D_2$ receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [$^{18}F$]FMBS by tail vein injection. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA $D_2$ receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA $D_1$ (SCH 23390), DA transporter (GBR 12909), and serotonin $S_2$ ($5-HT_2$) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabeled FMBS (1 mg/kg) and spiperone (1 mg/kg) reduced [$^{18}F$]FMBS striatal-to-cerebellar ratio by 41% and 80%, respectively. (+)-Butaclamol (1 mg/kg) blocked 80% of the striatal [$^{18}F$]FMBS binding, while (-)-butaclamol (1 mg/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect on [$^{18}F$]FMBS binding. Ketanserin (1 mg/kg), a ligand for the $5-HT_2$ receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [$^{18}F$]FMBS labels DA $D_2$ receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA $D_2$ receptors in vivo by PET.

• Journal of Life Science
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• v.32 no.1
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• pp.29-35
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• 2022

This study was conducted to analyze the genetic polymorphisms of dopamine receptor D4 (DRD4) in horse breeds and its association with substrate characteristics in Jeju crossbreds (Jeju Horse × Thoroughbred). Polymorphisms in DRD4 are candidate genes associated with temperament in various mammals, including humans. Single nucleotide polymorphism (SNP) G292A in the exon 3 region of the horse DRD4 has a reported association with curiosity and vigilance in thoroughbreds. Sanger sequencing was used to identify polymorphisms of the mutations in DRD4 in three horse breeds. The SNP frequency in Jeju horses was significantly different from the frequency in other breeds. Character evaluation, conducted in the Jeju crossbreds and scored using a temperament test and contact test, revealed a high correlation between each test. Comparison of the polymorphism in the DRD4 of horses and the results of the character evaluation revealed lower scores for all temperaments in horses carrying allele A. Comparison of the SNP of G292A and blood dopamine levels in Jeju crossbreds showed 2.87 times higher levels for the GA type than for the GG type. This study identified an association between DRD4 polymorphism and various test methods for evaluating horse temperament and levels of neurotransmitters. Further research could validate the use of this gene as a genetic marker for character evaluation.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.360-366
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• 2000

The in vivo binding of dopamine (DA) radioligands to $D_2$receptors can be affected by competition with endogenous dopamine. In the present study, we used a brain slice preparation that provides more controlled conditions than in vivo preparations in order to examine the relationship between synaptic DA and the binding of [$^3H$] raclopride to $D_2$receptors. We also estimated the synaptic DA concentration in rat striatal slices by determining the changes in [$^3H$] raclopride binding. To correlate the changes in [$^3$H]raclopride binding with the concentration of synaptic DA, the kinetic parameters were determined. [$^3H$] Raclopride reached equilibrium binding conditions within two hours. The K value for DA in inhibiting [$^3$H]raclopride binding was about 2.2 nM. The increase in synaptic DA evoked by electrical stimulation decreased the striatal binding of [$^3H$] raclopride in a frequency-dependent manner. Increases in the DA concentration evoked by amphetamine (AMPH) or cocaine decreased [$^3H$] raclopride binding by 74% or 20%, respectively, corresponding to increases in the synaptic DA concentrations of 1.6 nM or 0.6 nM, respectively. Pargyline also decreased [$^3H$] raclopride binding by 36%corresponding at a concentration of 1.2 nM. In contrast, the depletion of synaptic DA by $\alpha$-methyl-p-tyrosine ($\alpha$-MpT) increased the specific binding of [$^3H$] raclopride by 43%when the DA concentration was decreased to 0.7 nM. The changes in the DA concentration at the synapse were responsible for the changes in the striatal binding of [$^3H$] raclopride. The values calculated in this study may therefore approximate the changes in the synaptic DA concentration in rat striatal slices following manipulation.

• Korean Journal of Biological Psychiatry
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• v.2 no.2
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• pp.218-236
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• 1995

The author studied prognostic indicators of sixty Korean male alcoholics in psychological, social and biological aspects who were divided into abstinent and drinking groups. Thirty patients were assigned to each group. They were controlled in age and sex. Both groups were compared in terms of the demographic characteristics, past drinking history, treatment history, famaily history, ego strength and personality factors differences and distribution of dopamine $D_2$ receptor gene Al allele. Also the author studied relation of clinical course, alcoholic family history and dopamine $D_2$ receptor gene Al allele in both groups. The results were as follows; 1) The abstinent group had higher rate of married state, higher economic status, longer education years and maintained more stable job than the drinking group. But made no differences in occupation and religion. 2) The abstinent group showed higher rate of living with family members than the drinking group, and wives and fellows of the alcoholics anonymous were important factors for maintenance of abstinence. Family loading and parent's characters were not different. 3) The abstinent group had longer maximal length of abstinence but mean amount of alcohol consumption per day were larger than the drinking group. But there were no differences in duration of past drinking, drinking pattern, main drinking time, first drinking age and preference of the kind of alcoholic beverage in the past drinking history. 4) The abstinent group showed stronger treatment motivation, absolute abstinence in treatment goal, more voluntary adimission and maintained longer therapeutic relationship otter discharge than the drinking group. But both groups showed negative attitude toward antabuse therapy. 5) The abstinent group had higher mean score in ego strength scale than the drinking group. 6) In the personality factor questionnaire, the abstinent group showed strong laugh poise and the trait of praxernia, conservatism personality but the drinking group showed tough poise, the trait of weak ego strength(unstableness) and tough mindedness personality. 7) In comparision of dopamine $D_2$ receptor gene A1 allele, the prevalence of A1 allele was seventy percent and the frequency was 0.38 in the abstinent group. The prevalence of A1 allele was sixty percent and the frequency was 0.42 in the drinking group. Both groups were not significantly different in A1 allele prevalence and frequency. 8) In comparision of dopamine $D_2$ receptor gene A1 allele according to alcoholic family history, the prevalence of A1 allele was seventy percent and the frequency was 0.43 in the family history positive group. The prevalence of A1 allele was sixty-one percent and the frequency was 0.38 in the family history negative group. Both groups were not significantly different in A1 allele prevalence and frequency. In comparision of past drinking history according to alcoholic family history, the family history positive group showed earlier first drinking and problem drinking, but the family history negative group hod longer duration of past drinking. The mean amount of alcohol consumption per day, the longest duration of abstinence and Alcoholism Screening Test of Seoul Natoinal Mental Hospital(NAST) results were not significant. In conclusion, the results suggest that successful prognostic indicators of Korean alcoholics are married state, higher economic status, longer education years, stable job, living with family members, longer abstinence during past drinking history, strong treatment motivation, absolute abstinence in treatment goal, voluntary adimission, maintained therapeufic relationship, strong ego strength and the trait of praxernia, conservatism personality. But occupation, religion, alcoholic family history, parent's characters, duration of past drinking, drinking pattern, main drinking time, first drinking age, preference of the kind of alcoholic beverage, attitude to antabuse therapy and distribution of dopamine $D_2$ receptor A1 allele were not significantly related to the prognostic indicators of Korean alcoholics.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.240-244
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• 1996

The effects of chronic treatment with haloperidol on the binding capacities of dopamine(DA) $D_2$-like receptor were investigated in rat striatum and olfactory tubercle. The authors tried to confirm the dose-response effects with usual dose and low dose haloperidol. Rats were treated with haloperidol(0.05, 0.15, 0.5, 1.5mg/kg/day in drinking water) for four weeks. Saturation analysis of the binding of [$^3H$]spiperone to striatal membranes showed that the haloperidol treatment(0.05, 0.5, 1.5mg/kg) induced significant proliferation. The changes of dissociation constant(Kd) were not significant in striatum. The maximal binding density(Bmax) and Kd increased remarkably following the treatment with usual dose haloperidol (1.5mg/kg) in olfactory tubercle. Although there was increasing trend other the treatment with low dose haloperidol, the change of Bmax was not significant statistically. The present findings indicate that low dose haloperidol induces the proliferation of DA $D_2$-like receptor in striatum and interact with the dopaminergic transmission which might underlie the antipsychotic effect. This finding may support the recent clinical suggestion on the low dose strategy in the treatment of schizophrenia.