Tag Archives: RAF1

There is a growing evidence that serotoninergic systems modulate dopaminergic neurotransmission.

There is a growing evidence that serotoninergic systems modulate dopaminergic neurotransmission. in 2003 [11, 12]. In contrast to TPH1, which is expressed predominantly in the pineal gland and the periphery, TPH2 mRNA is expressed in the raphe nuclei [11]. Since the identification of TPH2, there have been numerous association analyses between gene variants and psychiatric diseases. For example, associations have been observed 121104-96-9 IC50 between variants and bipolar disorder [13-18], suicidal behavior in major depression [19-21], the response to selective serotonin reuptake inhibitors (fluoxetine and/or citalopram) [22, 23] and emotional regulation in healthy subjects [24-28]. These reports RAF1 indicate that polymorphic variants in the gene may have a role in the pathophysiology of a wide range of psychiatric disorders and emotional regulation. A recent study of heroin addiction also showed an association with variants in Hispanics and African-Americans [29]. The purpose of this study was (1) to identify novel sequence variations in all coding exons as well as exon-intron boundaries of the gene in Japanese, and (2) to investigate whether these polymorphisms and/or 121104-96-9 IC50 haplotypes were associated with METH dependence/psychosis. MATERIALS AND METHODS Subjects One-hundred sixty-two unrelated patients with METH dependence/psychosis (130 males and 32 females; mean age 37.412.0 years) meeting ICD-10-DCR criteria (F15.2 and F15.5) were used as case subjects; they were outpatients or inpatients of psychiatric hospitals. The 243 control subjects (168 males and 75 females; mean age 35.411.5 years) were mostly medical staff members who had neither personal nor familial history of drug dependence or psychotic disorders, as verified by a clinical interview. All subjects were Japanese, born and living in the northern Kyushu, Setouchi, Chukyo, Tokai, and Kanto regions. This study was approved by the ethical committees of each institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA), and all subjects provided written informed consent for the use of their DNA samples for this research [30]. After informed consent was obtained, blood samples were drawn and genomic DNA was extracted by the phenol/chloroform method. Defining Variants of the Gene Initially, 16 METH dependent/psychotic patient samples were used to identify nucleotide variants within the gene (GenBank accession no. “type”:”entrez-nucleotide”,”attrs”:”text”:”AC090109″,”term_id”:”15021970″,”term_text”:”AC090109″AC090109). Exons 1 to 11 and exon-intron boundaries were amplified by polymerase chain reaction (PCR) using a thermal cycler (Astec, Fukuoka, Japan), and the products were sequenced in both directions using BigDye terminators (Applied Biosystems, Foster City, CA) by an ABI Genetic analyzer 3100 (Applied Biosystems). Genotyping of each polymorphism except in exon 11 was performed by PCR amplification using the relevant primers listed in Table ?11 followed by sequencing using the same primers in both directions. Genotyping of polymorphisms in exon 11 was performed 121104-96-9 IC50 by PCR amplification using 9F and 11R primers followed by sequencing using 10F, 11F, and 11R primers. Table 1 Primers Used in this Study Patient Subgroups For the clinical category analysis, the patients were divided into two subgroups by three different clinical features. (A) Latency of psychosis from first METH intake: less than 3 years or more than 3 years. The course of METH psychosis varied among patients, with some patients showing psychosis sooner after the first METH intake, as previously reported [30, 31]. Because the median latency was three years, this time point was used as the cutoff in defining the two groups. (B) Duration of psychosis after the last METH intake: transient (<1 month) or prolonged ( R1 month). Some patients showed continuous psychotic symptoms even after METH discontinuation, as previously.