Further Evidence for an Association of 5-HTTLPR with Intensity Dependence of Auditory-Evoked Potentials

Abstract

Intensity dependence of auditory-evoked potentials (IAEP) has been suggested as an indicator of central serotonergic neurotransmission. Two recent studies investigated a possible association of IAEP with a functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) that has a short (s) and a long (l) variant. Although both studies found an association between 5-HTTLPR and IAEP, Gallinat et al found l/l individuals to exhibit lower IAEP, whereas Strobel et al observed stronger IAEP in l/l individuals. These conflicting results require further evaluation and more attention needs to be paid to variables that are known to be confounded with the effects of IAEP and 5-HTTLPR. Using a paradigm comparable to Strobel et al, the present study analyzes the effect of 5-HTTLPR on IAEP in a healthy male student sample (N=91; age=23 years, SD=1.9) that was homogenous for most significant confounding variables. A stronger IAEP was shown in l/l individuals, irrespective of the method of IAEP parametrization. This also held at retest after 3 weeks in a subsample (N=18). Given the successful replication of Strobel et al, several possible reasons for conflicting results with regard to Gallinat et al are discussed. It is argued that the most significant difference between Gallinat et al on the one hand, and Strobel et al and this study on the other, is that different intensity ranges are used which impact IAEP. Therefore, this study encourages further analysis of dose dependence of results.

Serotonin transporter gene variation impacts innate fear processing: acoustic startle response and emotional startle

“…Taking into account earlier findings on the impact of 5-HTTLPR on brain function, it can be subsumed that 5-HTTLPR differentially modulates multiple stages of information processing, ranging from (1) fast reflexes as demonstrated here and (2) early sensory processing as shown in recent event-related potential (ERP) studies [41][42][43] over (3) short-and middle-latency stages of more conscious emotional processing as observed in the imaging studies mentioned above, to (4) later processes of cognitive response control and error processing as evidenced in the ERP studies of Fallgatter et al, 44,45 who were the first to report an association between 5-HTTLPR and prefrontal cortex-limbic excitability in a Go-NoGo task and an error-processing task. As different kinds of the startle paradigm afford to examine information processing at several stages, the startle paradigm can be seen as an integrative tool to further our understanding of the serotonergic influences on complex behavior.…”

Effects of selective and combined serotonin and dopamine depletion on the loudness dependence of the auditory evoked potential (LDAEP) in humans

“…For example, while a stronger LDAEP has been linked with low cerebrospinal fluid (CSF) levels of the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA) in humans (Von Knorring and Perris, 1981), increasing serotonin with the selective serotonin reuptake inhibitor (SSRI), citalopram, has been shown to decrease (Nathan et al, 2006) and have no effects (Uhl et al, 2006;Guille et al, 2007) on the LDAEP. Studies examining a functional polymorphism in the promoter region of the serotonin transporter (SERT) gene (5-HTTLPR) have shown a stronger LDAEP in subjects homozygous for the l allele (associated with higher 5-HTT expression and higher serotonin re-uptake) (Hensch et al, 2006;Strobel et al, 2003) as well as in subjects homozygous for the s allele (associated with lower 5-HTT expression and lower serotonin re-uptake) . These results suggest that earlier findings in patients may need to be interpreted with caution due to the possible confounds of disease in such populations and additionally, the link between serotonin and the LDAEP has not been consistently supported by direct genetic studies.…”

Intensity dependence of auditory P2 in monozygotic twins discordant for Vietnam combat: Associations with posttraumatic stress disorder

“…Two studies found that individuals with long (l) forms of the 5-HTTLPR genotype (or l/l genotype) demonstrated increased intensity dependence [30][31], whereas the third study found that individuals with the l/l genotype demonstrated decreased intensity dependence [32]. The short (s) form of the 5-HTTLPR allele (or s allele) impairs gene transcription and reduces 5-HTTLPR levels and reuptake compared with the l/l genotype [33], purportedly resulting in higher 5-HT availability.…”