title: Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression.
abstract: 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.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge,C-168,SE-141 86 Stockholm, Sweden.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kishida
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawanishi
authors.forename: Leif
authors.initials: L
authors.lastname: Bertilsson
authors.forename: Hans
authors.initials: H
authors.lastname: Agren
mesh_terms: D000328:Adult; D000368:Aged; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D001923:Brain Chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000503:physiopathology; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015306:Biogenic Monoamines; D050486:Serotonin Plasma Membrane Transport Proteins; C030284:3-methoxy-4-hydroxyphenylglycol sulfate; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid