Functional cortical effects of novel allelic variants of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in humans.
BACKGROUND
Genetic variations of the serotonin transporter-linked polymorphic region (5-HTTLPR) have been implicated in the pathogenesis of several psychiatric disorders. Recent evidence indicates that the biallelic polymorphic region (S and L allele) contains additional variations affecting the mRNA expression.


METHODS
According to recent preclinical and clinical studies, the loudness dependence of auditory evoked potentials (LD) was investigated as surrogate parameter for the central serotonergic activity in 185 healthy subjects subdivided according to newly identified 5-HTTLPR genotypes.


RESULTS
Individuals homozygous for the L (A) allele showed the lowest LD of all genotypes suggesting a high serotonergic neurotransmission. The other observed genotypes (L (A)/L (G), S/L (A), S/L (G), S/S) had an LD which was similar to each other but higher compared to the L (A)/L (A) genotype.


CONCLUSIONS
The data provide a rationale to subdivide the L allele of the 5-HTTLPR into L (A) and L (G) alleles in terms of their serotonin activity as indicated by the LD. The present IN VIVO measurements provide a basis for grouping the L (G) and S alleles for further investigations.
Gallinat
J
J
Clinic for Psychiatry and Psychotherapy, Charité Medicine Berlin, Campus Charité Mitte, Berlin, Germany. juergen.gallinat@charite.de
Müller
D J
DJ
Bierbrauer
J
J
Rommelspacher
H
H
Juckel
G
G
Wernicke
C
C
D000328:Adult; D000483:Alleles; D002540:Cerebral Cortex / Q000502:physiology*; D004247:DNA / Q000235:genetics; D005072:Evoked Potentials, Auditory / Q000235:genetics / Q000502:physiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012701:Serotonin / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics
D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004247:DNA