Details of a Researcher - KAWANISHI Chiaki

Papers - KAWANISHI Chiaki

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Unexpectedly high prevalence of akathisia in cancer patients

Chiaki Kawanishi, Hideki Onishi, Daiji Kato, Ikuko Kishida, Taku Furuno, Makoto Wada, Yoshio Hirayasu

Palliative and Supportive Care 5 ( 4 ) 351 - 354 2007.12 [Refereed]

Objectives: Complications of neuropsychiatric disorders are often detected in cancer patients. Adjustment disorders, depression, or delirium are common psychiatric disorders in these patients, and drug-induced neuropsychiatric problems are sometimes referred for psychiatric consultation. Prochlorperazine and other antiemetic drugs that are phenothiazine derivates are also reported to cause akathisia due to the blockade of the dopamine receptor in the central nervous system, but the prevalence of akathisia in patients undergoing cancer treatment has not been reported. This study seeks to explore the prevalence of such drug-induced syndromes (e.g., akathisia) in this population. Methods: This present study was a prospective study. The subjects of this study were 483 consecutive patients with cancer who had been referred to the Department of Psychiatry in Kanagawa Prefecture Cancer Center from February 1, 2004, to November 30, 2005. Trained psychiatrists conducted a nonstructured psychiatric interview and neurologic examination to establish psychiatric diagnoses according to DSM-IV and the presence or absence of drug-induced extra pyramidal symptoms. The past and current medications used in their cancer treatment were also examined in detail for an accurate evaluation. Results: A psychiatric diagnosis was made in 420 (87.0%) of the 483 cancer patients examined, and akathisia, a drug-induced movement disorder, was unexpectedly prevalent among the patients 20 of 420 (4.8%) patients had developed akathisia from an antiemetic drug, prochlorperazine. Significance of results: Diagnosing such adverse drug reactions may be difficult due to complicating factors in cancer treatment, and the inner restlessness observed in akathisia is likely to be regarded as a symptom of a primary psychiatric disorder. The authors suggest that oncologists should optimize the use of antiemetic drugs and be aware of akathisia as a possible complication of cancer treatment. © 2007 Cambridge University Press.

Detection and treatment of akathisia in advanced cancer patients during adjuvant analgesic therapy with tricyclic antidepressants: Case reports and review of the literature

Hideki Onishi, Wataru Yamamoto, Makoto Wada, Tomomi Nishida, Mei Wada, Yu Sunagawa, Toshimichi Miya, Chiaki Kawanishi, Masaru Narabayashi, Yasutsuna Sasaki

Palliative and Supportive Care 5 ( 4 ) 411 - 414 2007.12 [Refereed]

Objective: There is substantial evidence that tricyclic antidepressants are effective in the management of chronic pain, including cancer pain. In oncological settings, these agents are used as adjuvant analgesic drugs. However, cases of akathisia due to tricyclic antidepressants used as adjuvant analgesic therapy have not previously been reported. Case reports: Two cancer patients experiencing chronic pain who were refractory to nonsteroidal anti-inflammatory drugs and opioids were prescribed amoxapine as an adjuvant analgesic therapy for neuropathic pain. These patients developed inner restlessness and restless physical movements after amoxapine was prescribed. Although symptoms were atypical, akathisia was suspected and discontinuation of amoxapine resolved the symptoms. Results and significance of results: Akathisia should be considered in patients receiving adjuvant analgesic therapy with tricyclic antidepressants. Early detection and appropriate treatment will relieve this distressing symptom. Restless movements involving parts of the body other than the legs may be the clue to the diagnosis. © 2007 Cambridge University Press.

Psychiatric assessment of suicide attempters in Japan: A pilot study at a critical emergency unit in an urban area

Tomoki Yamada, Chiaki Kawanishi, Hana Hasegawa, Ryoko Sato, Akiko Konishi, Daiji Kato, Taku Furuno, Ikuko Kishida, Toshinari Odawara, Mitsugi Sugiyama, Yoshio Hirayasu

BMC Psychiatry 7 2007.11 [Refereed]

Background: The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan. Methods: Three hundred and twenty consecutive cases of attempted suicide who were admitted to an urban emergency department were interviewed, with the focus on psychosocial background and DSM-IV diagnosis. Moreover, they were divided into two groups according to the method of attempted suicide in terms of lethality, and the two groups were compared. Results: Ninety-five percent of patients received a psychiatric diagnosis: 81% of subjects met the criteria for an axis I disorder. The most frequent diagnosis was mood disorder. The mean age was higher and living alone more common in the high-lethality group. Middle-aged men tended to have a higher prevalence of mood disorders. Conclusion: This is the first large-scale study of cases of attempted suicide since the dramatic increase in suicides began in Japan. The identification and introduction of treatments for psychiatric disorders at emergency departments has been indicated to be important in suicide prevention. © 2007 Yamada et al licensee BioMed Central Ltd.

Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome

Daiji Kato, Chiaki Kawanishi, Ikuko Kishida, Taku Furuno, Kyoko Suzuki, Hideki Onishi, Yoshio Hirayasu

European Journal of Clinical Pharmacology 63 ( 11 ) 991 - 996 2007.11 [Refereed]

Objective: Neuroleptic malignant syndrome (NMS) is one of the most serious adverse reactions to antipsychotic medications. We accumulated data on Japanese NMS patients and, in a study designed to examine the effects of drug metabolism on the occurrence of NMS, tested the possibility of association between NMS and CYP2D6 polymorphisms. Methods: We studied 53 patients who had experienced NMS and 112 healthy individuals. We determined what drugs the patients with NMS had been given and retrospectively identified candidates for drugs causing NMS. We screened the prevalence of CYP2D6 genotypes using polymerase chain reaction and restriction fragment length polymorphism analyses. Results: The prevalence of *5 alleles in the group of all patients with NMS was higher than that in the controls, though this difference was not statistically significant (10.4% vs. 5.4% P=0.107 odds ratio (OR) 2.05 95% confidence interval (CI) 0.87-4.80). No association was found between the frequency of *10 alleles and the occurrence of NMS. We found *4 and duplicated alleles in only one patient each among the patients with NMS. A total of 29 patients appeared to have developed NMS as a result of having taking CYP2D6 substrates. The prevalence of *5 alleles in these 29 patient was significantly higher than that in the controls (15.5% vs. 5.4% P=0.020 OR 3.25 95% CI 1.30-8.13). Conclusion: Our findings suggest that the CYP2D6*5 allele is likely to affect vulnerability to development of NMS. © 2007 Springer-Verlag.

Neuronal and glial accumulation of α- and β-synucleins in human lipidoses

Kyoko Suzuki, Eizo Iseki, Takashi Togo, Akira Yamaguchi, Omi Katsuse, Kayoko Katsuyama, Seiichi Kanzaki, Kazumasa Shiozaki, Chiaki Kawanishi, Sumimasa Yamashita, Yukichi Tanaka, Shoji Yamanaka, Yoshio Hirayasu

Acta Neuropathologica 114 ( 5 ) 481 - 489 2007.11 [Refereed]

A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both α- and β-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although α-synuclein has been implicated in several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear. In our present study, we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay - Sachs disease, metachromatic leukodystrophy, β-galactosialidosis and adrenoleukodystrophy, for the expression of α- and β-synucleins and the associated lipid storage levels. The accumulation of α-synuclein was found in brain tissue in not only cases of lysosomal storage diseases, but also in instances of adrenoleukodystrophy, which is a peroxisomal disease. α-synuclein was detected in both neurons and glial cells of patients with these two disorders, although its distribution was found to be disease-dependent. In addition, α-synuclein-positive neurons were also found to be NeuN-positive, whereas NeuN-negative neurons did not show any accumulation of this protein. By comparison, the accumulation of α-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of α- and β-synucleins in human lipidoses may be related to functional differences between these two proteins. In addition, the accumulation of α-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids. © Springer-Verlag 2007.

Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression

Ikuko Kishida, Eleni Aklillu, Chiaki Kawanishi, Leif Bertilsson, Hans Ågren

Neuropsychopharmacology 32 ( 10 ) 2143 - 2151 2007.10 [Refereed]

The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders. © 2007 Nature Publishing Group All rights reserved.

Perospirone in treatment of Huntington's disease: A first case report

Tomohide Roppongi, Takashi Togo, Shinichi Nakamura, Takeshi Asami, Asuka Yoshimi, Kazumasa Shiozaki, Daiji Kato, Chiaki Kawanishi, Yoshio Hirayasu

Progress in Neuro-Psychopharmacology and Biological Psychiatry 31 ( 1 ) 308 - 310 2007.01 [Refereed]

Huntington's disease (HD) is a hereditary disorder clinically characterized by involuntary movements, cognitive decline and psychiatric symptoms. We report on a patient with HD, whose involuntary movements and psychiatric symptoms were clinically improved with perospirone, a second-generation antipsychotic agent with antagonistic effects on serotonin 5-HT2A and dopamine D2 (D2) receptors, as well as a unique agonistic effect on serotonin 5-HT1A (5-HT1A) receptors. The fact that perospirone antagonizes D2 receptors could explain its effects on the hyperkinetic syndrome, while its agonistic effects on 5-HT1A receptors may explain the amelioration of psychiatric symptoms (fear and anxiety) in this patient. Future studies would be valuable to elucidate the utility of perospirone for the treatment of involuntary movements and psychiatric symptoms in HD. © 2006 Elsevier Inc. All rights reserved.

Knowledge and attitude towards suicide among medical students in Japan: Preliminary study

Ryoko Sato, Chiaki Kawanishi, Tomoki Yamada, Hana Hasegawa, Haruka Ikeda, Daiji Kato, Taku Furuno, Ikuko Kishida, Yoshio Hirayasu

Psychiatry and Clinical Neurosciences 60 ( 5 ) 558 - 562 2006.10 [Refereed]

Japan has one of the highest suicide rates in the world. Suicides numbered 32 863 in 1998 and have exceeded 30 000 in every subsequent year. Education of those involved in general and psychosocial patient care can contribute greatly to suicide prevention. The authors administered a brief knowledge and attitude assessment questionnaire concerning suicide to students in their first, third, and fifth years at a Japanese medical school. Participants numbered 160 (94 men with a mean age of 21.8 years, SD = 3.01, and 66 women with a mean age of 21.2 years, SD = 2.64) 59 first year, 52 third year, and 49 in their fifth year. The questionnaire consists of eight multiple-choice questions asking knowledge of suicide and one open-ended question asking attitude. In the knowledge part, only about half of the items were answered correctly (mean score was 4.21, SD = 1.28). A significant difference was observed in prevalence of attitudes as categorical variables between student years (P = 0.001). Sympathetic comments increased along with student years, while critical comments decreased. Given the frequent and interventional opportunities of primary-care medical contacts, poor understanding of suicide from the medical viewpoint was of concern. Moreover, judgmental attitudes were common, especially in earlier school years. Better informed, more understanding physicians and other health professionals could contribute greatly to prevention. © 2006 The Authors.

Quetiapine-induced neuroleptic malignant syndrome in dementia with Lewy bodies: A case report

Akiko Kobayashi, Chiaki Kawanishi, Takehiko Matsumura, Daiji Kato, Ryoko Furukawa, Ikuko Kishida, Yoshio Hirayasu

Progress in Neuro-Psychopharmacology and Biological Psychiatry 30 ( 6 ) 1170 - 1172 2006.08 [Refereed]

Patients with dementia with Lewy bodies (DLB) are particularly vulnerable to adverse effects of neuroleptics this sensitivity is included among the clinical diagnostic criteria for DLB. Recently atypical neuroleptics, which carry less risk of extrapyramidal side effects than typical agents, have come into increasing use in treating psychotic symptoms and behavioral disturbances related to DLB. The present report is the first to describe a DLB patient who developed neuroleptic malignant syndrome (NMS) induced by quetiapine, an atypical neuroleptic known to have relatively infrequent extrapyramidal side effects in DLB patients. Physicians should be aware of the possibility of the occurrence of NMS in DLB even when atypical neuroleptics are administered. © 2006 Elsevier Inc. All rights reserved.

CYP2D6 gene deletion allele in patients with neuroleptic malignant syndrome: Preliminary report

Daiji Kato, Chiaki Kawanishi, Ikuko Kishida, Taku Furuno, Takehiko Matsumura, Hana Hasegawa, Kyoko Suzuki, Yoshio Hirayasu

Psychiatry and Clinical Neurosciences 59 ( 4 ) 504 - 507 2005.08 [Refereed]

Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse reaction to psychopharmacologic treatment. Reported herein are two NMS patients with schizophrenia who were found to possess a CYP2D6 gene deletion allele (CYP2D6*5). The deletion results in decreased CYP2D6 activity, possibly leading to drug accumulation. Both patients with NMS had been treated with neuroleptics, including CYP2D6 substrates. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analyses and long PCR were performed to detect CYP2D6 genotype. One patient was found to possess *5/*10 the other had a *1/*5 genotype. The present preliminary report suggests that pharmacokinetic factors cannot be excluded and the CYP2D6 polymorphism is possibly associated with the etiology of NMS.

[Mandatory postgraduate training in psychiatry in Yokohama City University and the affiliated medical facilities under the new system of postgraduate clinical education in Japan].

Reiko Sato, Chiaki Kawanishi, Kazumasa Shiosaki, Naoya Sugiyama, Shuichiro Fujiwara, Atsushi Ozawa, Toshinari Odawara, Yoshio Hirayasu

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 107 ( 8 ) 841 - 5 2005 [Domestic journal]

Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: Ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study

Chiaki Kawanishi, Stefan Lundgren, Hans Ågren, Leif Bertilsson

European Journal of Clinical Pharmacology 59 ( 11 ) 803 - 807 2004.01 [Refereed]

Objective: Recent studies have revealed that genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are among the factors that determine the interindividual differences in the metabolism and response to antidepressants. We investigated the relationship between persistent mood disorders and the duplication of the CYP2D6 gene, which encodes an enzyme with increased activity. Methods: We screened the prevalence of the CYP2D6 genotypes in 108 patients with persistent mood disorders using long polymerase chain reaction (PCR) and the real-time PCR methods. Clinical correlates with the genotypes were also analyzed. Results: Among the 108 patients, 81 had failed to respond to antidepressants shown to be metabolized by CYP2D6. Of those 81, 8 had a CYP2D6 gene duplication (9.9%, 95% confidence interval 3.4-16.4%) which was higher than the 0.8-1.0% incidence previously observed in healthy Nordic Caucasians. The worst week scores of the Hamilton Depression Rating Scale were higher in the patients with the duplication compared with those without the duplication (P = 0.026, student's t-test). Conclusion: These results suggest that the CYP2D6 gene duplication is a possible factor that influences the development of persistence in patients with mood disorders probably by ultrarapid drug metabolism.

Lack of association in Japanese patients between neuroleptic malignant syndrome and the TaqI A polymorphism of the dopamine D2 receptor gene

Ikuko Kishida, Chiaki Kawanishi, Taku Furuno, Takehiko Matsumura, Hana Hasegawa, Naoya Sugiyama, Kyoko Suzuki, Yoshiteru Yamada, Kenji Kosaka

Psychiatric Genetics 13 ( 1 ) 55 - 57 2003.03 [Refereed]

Objective: The molecular basis of neuroleptic malignant syndrome (NMS) is unclear, but clinical studies have noted a genetic predisposition. A recent genetic study suggested an association between NMS and the TaqI A polymorphism in the dopamine D2 receptor (DRD2) gene. We further examined the association in a larger number of subjects. Methods: We studied 49 Japanese patients previously diagnosed with NMS, and 123 schizophrenic patients treated with neuroleptics without occurrence of NMS. PCR and RFLP analyses were performed to screen the TaqI A polymorphism. Results: The TaqI A1 allele frequency was 0.408 in NMS patients and 0.415 in patients without NMS. No significant differences in allelic or genotypic frequencies were observed between the two groups. Conclusions: We cannot conclude that the TaqI A polymorphism is associated with development of NMS. © 2003 Lippincott Williams & Wilkins.

A patient with treatment-resistant schizophrenia and cytochrome P4502D6 gene duplication

Chiaki Kawanishi, T. Furuno, I. Kishida, T. Matsumura, K. Kosaka

Clinical Genetics 61 ( 2 ) 152 - 154 2002.02 [Refereed]

No evidence of an association between CYP2D6 polymorphisms among Japanese and dementia with Lewy bodies

Taku Furuno, Chiaki Kawanishi, Eizo Iseki, Hideki Onishi, Naoya Sugiyama, Kyoko Suzuki, Kenji Kosaka

Psychiatry and Clinical Neurosciences 55 ( 2 ) 89 - 92 2001 [Refereed]

Dementia with Lewy bodies (DLB) is the second most frequent degenerative dementia among the elderly, following Alzheimer-type dementia (ATD). An association of DLB with CYP2D6*4, one of the cytochrome P450IID6 (debrisoquine 4-hydroxylase CYP2D6) gene polymorphisms, was reported previously, but this is controversial. Moreover, these reports have been restricted to Caucasian populations. Therefore, we compared frequencies of CYP2D6*3, *4, and *10 mutant alleles in 17 Japanese DLB patients to those among Alzheimer-type dementia (ATD) patients and healthy controls. Polymerase chain reaction amplification and restriction fragment length polymorphism analyses were used for genotyping. No significant difference of genotype or mutant allele frequencies was detected between DLB, ATD, and healthy controls. The present results do not support the suggestion that the CYP2D6 gene is related to DLB susceptibility, at least in the Japanese population.

Pelizaeus-Merzbacher disease: Three novel mutations and implication for locus heterogeneity

Hitoshi Osaka, Chiaki Kawanishi, Ken Inoue, Hideki Onishi, Takuya Kobayashi, Naoya Sugiyama, Kenji Kosaka, Atsuo Nezu, Katsunori Fujii, Katsuo Sugita, Kazuo Kodama, Keiko Murayama, Shigeo Murayama, Ichiro Kanazawa, Seiji Kimura

Annals of Neurology ( Wiley ) 45 ( 1 ) 59 - 64 1999.01 [Refereed]

Mutation involving cytochrome P450IID6 in two Japanese patients with neuroleptic malignant syndrome

Chiaki Kawanishi, Yoshikazu Shimoda, Jun Fujimaki, Hideki Onishi, Kyoko Suzuki, Tokiji Hanihara, Naoya Sugiyama, Kenji Kosaka

Journal of the Neurological Sciences 160 ( 1 ) 102 - 104 1998.09 [Refereed]

Japanese Creutzfeldt-Jakob disease patients exhibiting high incidence of the E200k PRNP mutation and located in the basin of a river

Tomohiro Miyakawa, Ken Inoue, Eizo Iseki, Chiaki Kawanishi, Naoya Sugiyama, Hideki Onishi, Yoshiteru Yamada, Kyoko Suzuki, Kiyoshi Iwabuchi, Kenji Kosaka

Neurological Research ( Forefront Publishing Group ) 20 ( 8 ) 684 - 688 1998 [Refereed]

Seven cases with Creutzfeldt-Jakob disease (CJD) located in the basin of the Fuji river (Fuji area) in Japan were examined genetically and clinicopathologically. The onset of the disease was between 1989 and 1995. All cases were from different families, although 3 cases were family members of previously reported CJD patients. They had clinical and/or neuropathological features, corresponding to subacute spongiform encephalopathy. Five of the 7 cases, including the 3 familial cases, had the E200K mutation in the gene encoding prion protein (PRNP). It is suggested that there is a small cluster of CJD patients with a founder effect of the E200K mutation in the Fuji area, because the incidence of CJD with the E200K mutation appears to be much higher in this area than other areas in Japan. The disease penetrance of the 5 cases with the E200K mutation seems to be low, and they may have an age-related incidence in the Fuji area. These findings support the hypothesis that the phenotypes of CJD patients with the PRNP mutations are linked to the position of the mutation, but not related to ethnic or environmental factors.

Pancreatic exocrine dysfunction associated with mitochondrial tRNA(Leu(UUR)) mutation

Hideki Onishi, Tokiji Hanihara, Naoya Sugiyama, Chiaki Kawanishi, Eizo Iseki, Yasuko Maruyama, Yoshiteru Yamada, Kenji Kosaka, Saburo Yagishita, Hisahiko Sekihara, Shinobu Satoh

Journal of Medical Genetics 35 ( 3 ) 255 - 257 1998 [Refereed]

We report on pancreatic exocrine dysfunction in families that have the mitochondrial tRNA(Leu(UUR)) gene mutation. These families exhibited maternally inherited diabetes mellitus (DIM) and an A to G substitution at nt 3243 of the mitochondrial tRNA(Leu(UUR)) gene (A3243G mutation). Pancreatic necropsy samples from one proband showed accumulation of degenerated mitochondria in pancreatic acinar cells. Pancreatic exocrine dysfunction was recognised by a functional pancreatic study. This study indicates that exocrine pancreatic dysfunction may be associated with the A3243G mutation.

Lack of association between neuroleptic malignant syndrome and polymorphisms in the 5-HT(1A) and 5-HT(2A) receptor genes

Chiaki Kawanishi, Tokiji Hanihara, Yoshikazu Shimoda, Kyoko Suzuki, Naoya Sugiyama, Hideki Onishi, Tomohiro Miyakawa, Yoshiteru Yamada, Kenji Kosaka

American Journal of Psychiatry ( American Psychiatric Association ) 155 ( 9 ) 1275 - 1277 1998 [Refereed]

Objective: The molecular basis of neuroleptic malignant syndrome is unclear, but studies suggest that genetic factors are involved in its pathogenesis. Considering possible involvement of the serotonergic system in neuroleptic malignant syndrome, the authors examined the association between neuroleptic malignant syndrome and polymorphisms of the 5-HT(1A) and 5- HT(2A) receptor genes. Method: The authors examined the frequencies of gene polymorphisms in the 5-HT(1A) (Arg219Leu) and 5-HT(2A) (Thr25Asn and His452Tyr) receptor genes in 29 patients previously diagnosed with neuroleptic malignant syndrome, 94 neuroleptic-treated patients with schizophrenia who had no history of neuroleptic malignant syndrome, and 94 healthy comparison subjects. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to screen gene mutations. Results: No polymorphic allele was detected in the patients who had experienced the neuroleptic malignant syndrome. Conclusions: The authors cannot conclude that polymorphisms in the 5-HT(1A) and 5HT(2A) receptor genes are factors determining susceptibility to the neuroleptic malignant syndrome.

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