uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Further evidence for an association of 5-HTTLPR with intensity dependence of auditory-evoked potentials
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Show others and affiliations
2006 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1470-634X, Vol. 31, no 9, 2047-2054 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 31, no 9, 2047-2054 p.
Keyword [en]
serotonin transporter, genetic polymorphism, 5-HTTLPR, endophenotype, auditory-evoked potentials, intensity dependence
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-102700DOI: 10.1038/sj.npp.1301020ISI: 000239920400021PubMedID: 16421513OAI: oai:DiVA.org:uu-102700DiVA: diva2:216675
Available from: 2009-05-11 Created: 2009-05-11 Last updated: 2011-05-27Bibliographically approved
In thesis
1. The Relation between Serotonergic Biomarkers and Behaviour: – studies on human primates, non-human primates and transgenic mice
Open this publication in new window or tab >>The Relation between Serotonergic Biomarkers and Behaviour: – studies on human primates, non-human primates and transgenic mice
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rationale: The serotonergic system is involved in the modulation of emotion and plays an important role for personality and vulnerability for psychiatric disorders. In the papers included in this thesis, we investigate three biological factors that have been studied in relation to psychiatric symptoms: Platelet monoamine oxidase B (MAO-B) activity, and variations in the MAO-A and the serotonin transporter (5HTT) genes. We also study intensity dependent auditory evoked potentials (IAEP) as an intermediate phenotype for serotonergic capacity. Platelet MAO-B has been shown to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores of sensation seeking, monotony avoidance, and impulsiveness, as well as for susceptibility for alcoholism. Functional polymorphisms in the promoter of the genes encoding MAO-A and the serotonin transporter result in high- or low- activity alleles that have been associated with numerous psychiatric symptoms. One hypothesis for the shaping of personality is that these genotype variants have prenatal effects on the wiring of the brain. Thus, exploring how the development of the brain is affected by different prenatal serotonin levels is relevant in this context.

Observations: (i) Platelet MAOB activity was associated with monoamine metabolites in cerebrospinal fluid from cisterna magna in monkeys, as well as with voluntary alcohol intake, alcohol-induced aggression, and alcohol sensitivity. (ii) The long 5HTTLPR allele was associated with increased IAEP. (iii) The functional MAOA and 5HTT polymorphisms were associated with symptoms of ADHD-related traits in a population based sample of Swedish adolescents. Associations of these candidate genes with ADHD scores were strenghtened when the platelet MAOB activity was combined with genotype. (iv) Our pilot data showed that treatment of pregnant mice with 5HTT blocking antidepressives resulted in more serotonergic cellbodies in lateral wings of dorsal raphe in the offspring, when compared to saline treatment.

Conclusions: Our studies support the notion that platelet MAOB activity and IAEP are endophenotypes for monoaminergic capacity and related behaviours. The functional candidate polymorphisms in MAOA and 5HTT were linked to behaviour, however, the cause-relationship is unclear and the explanation for the associations need to be further investigated, possibly with focus on prenatal effects of the polymorphisms.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 57 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 676
Serotonin, MAO-A, 5-HTT, MAO-B, alcohol, ADHD
National Category
Medical and Health Sciences
Research subject
Medicine; Neuroscience
urn:nbn:se:uu:diva-151870 (URN)978-91-554-8091-2 (ISBN)
Public defence
2011-06-11, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Available from: 2011-05-20 Created: 2011-04-18 Last updated: 2011-07-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Wargelius, Hanna-Linn
By organisation
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 191 hits
ReferencesLink to record
Permanent link

Direct link