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Associations of MAOA-VNTR or 5HTT-LPR alleles with attention-deficit hyperactivity disorder symptoms are moderated by platelet monoamine oxidase B activity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Karolinska Institutet, Department of Woman and Child Health, Child and Adolescent Psychiatric Unit .
Karolinska Institutet, Department of Woman and Child Health, Child and Adolescent Psychiatric Unit .
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
2012 (English)In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 22, no 1, 42-45 p.Article in journal (Refereed) Published
Abstract [en]

The monoamine systems have been suggested to play a role in the biological basis of ADHD symptoms. Thus, polymorphisms in e.g. the monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) genes have been associated with ADHD like phenotypes. Furthermore, platelet MAOB activity has frequently been linked to impulsiveness-related traits. In the present paper, we have studied ADHD symptoms with regard to the combination of platelet MAOB activity and MAOAVNTR or 5HTT-LPR genotype.

The study group consisted of 156 adolescent twin pairs, i.e. 312 individuals, who were used in a previous study (Malmberg et al., 2008). ADHD symptoms were scored with a structured clinical interview of both the twin and a parent using Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Presence of a short 5HTT-LPR or short MAOA-VNTR allele, in combination with high levels of platelet MAOB enzyme activity was associated with higher scores of ADHD like problems (p<0.001; p<0.01, respectively).

This reexamination of ADHD scores in a non-clinical sample suggests that effects of the MAOA-VNTR and 5HTT-LPR are moderated by platelet MAOB activity.

 

Place, publisher, year, edition, pages
2012. Vol. 22, no 1, 42-45 p.
Keyword [en]
ADHD, ODD, conduct disorder, candidate genes, MAO-A, 5HTT, platelet MAO-B
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-151865DOI: 10.1097/YPG.0b013e328347c1abISI: 000298376800005PubMedID: 21610556OAI: oai:DiVA.org:uu-151865DiVA: diva2:411686
Available from: 2011-04-19 Created: 2011-04-18 Last updated: 2017-12-11Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 676
Keyword
Serotonin, MAO-A, 5-HTT, MAO-B, alcohol, ADHD
National Category
Medical and Health Sciences
Research subject
Medicine; Neuroscience
Identifiers
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)
Opponent
Supervisors
Available from: 2011-05-20 Created: 2011-04-18 Last updated: 2011-07-01Bibliographically approved

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Wargelius, Hanna-LinnOreland, Lars

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