Primary structure of the serotonin transporter in unipolar depression and bipolar disorder.
Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites/transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTT) as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-III-R diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose nucleic acid (cDNA) synthesized from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screened), although a conservative single-base substitution representing a silent polymorphism was found. The results provide preliminary evidence that alterations in the primary structure of 5-HTT are not generally involved in the pathogenesis of unipolar depression and manic-depressive illness.
Lesch
K P
KP
Department of Psychiatry, University of Wuerzburg, Germany.
Gross
J
J
Franzek
E
E
Wolozin
B L
BL
Riederer
P
P
Murphy
D L
DL
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000737:chemistry; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins