Abstract
It has been proposed that the loudness dependence of auditory evoked potentials (LDAEP) would be a reliable indicator of central serotonin system activity in humans. Serotonin levels and turnover are also increased by brain-derived neurotrophic factor (BDNF). The aim of the present study was to determine whether there is an association between genetic polymorphisms of BDNF and the LDAEP in healthy Korean young adults. The cohort comprised 211 mentally and physically healthy subjects, all of whom were nonsmokers (111 males, 100 females; age: 20∼32 years). To avoid hormonal effects, the LDAEP was measured during days 2–5 after the beginning of menstruation for female subjects. In addition, BDNF polymorphisms (rs6265, rs2030324, and rs1491850) were genotyped. The strength of the LDAEP differed significantly among the BDNF genotype groups. Furthermore, the distribution of genotypic frequencies differed significantly between subjects with high and low LDAEPs. In particular, subjects with the Val/Met (A/G) genotype for rs6265, the T/T genotype for rs2030324, or the C/C genotype for rs1491850 had a higher LDAEP, indicating lower central serotonergic activity. A low LDAEP was more prevalent than a high LDAEP among those with the C-T haplotype (C genotype for rs2030424 and T genotype for rs1491850). Our results concur with previous findings on BDNF polymorphisms and serotonergic drug responses in psychiatric disorder patients. The present results suggest the possibility that BDNF polymorphisms and LDAEP patterns can predict altered serotonergic activity.
Highlights
It has been proposed the loudness dependence of auditory evoked potentials (LDAEP) is a reliable indicator of central serotonin system activity in humans [1,2]
The genotypic frequencies of the three brain-derived neurotrophic factor (BDNF) gene polymorphisms conformed with Hardy-Weinberg equilibrium
The frequency of one haplotype (C-T) differed significantly between the low- and high-LDAEP groups at Cz (55% vs. 42%, respectively; p = 0.000; Table 2). This was a replication study, in that it had the same design as that of Juckel and colleagues [20]. This is the first study to show an association between BDNF single-nucleotide polymorphisms (SNPs) [rs6265(Val/Met), rs2030324, and rs1491850] and the LDAEP in an Asian population
Summary
It has been proposed the loudness dependence of auditory evoked potentials (LDAEP) is a reliable indicator of central serotonin system activity in humans [1,2]. The LDAEP reflects the change in the auditory evoked N1/P2 component evoked by an increase in stimulus intensity and has been found to be inversely associated with central nervous system serotonergic activity [3], such that a weak LDAEP reflects high serotonergic neurotransmission, and vice versa [4] From these findings it has been proposed that the LDAEP is a biological marker of central serotonergic activity in major depressive disorder and other psychiatric diseases [1,5,6]. There is evidence that acute treatment rapidly activates TrkB (tropomyosin-related kinase B) receptors, which are related to BDNF [18] This effect is not observed in serotonin-depleted mice, which points to the crucial role of serotonin in increasing the actions of BDNF on its receptor [18]
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