| 1. |
- Dahlgren, Angelica, et al.
(author)
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Do Alcohol-dependent individuals with DRD2 A1 allele have an increased risk of relapse? A pilot study
- 2011
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In: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 46:5, s. 509-513
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Journal article (peer-reviewed)abstract
- Aims: The TaqIA polymorphism of the dopamine D2 receptor (DRD2) gene has been extensively studied in relation to alcoholism, and the TaqI A1 allele appears to be over-represented in alcohol-dependent individuals. In a recent study, this allele has also been associated with a highly increased mortality rate in alcohol-dependent individuals. In the present study, we investigated whether the TaqI A1 allele of the DRD2 gene region was associated with a higher relapse rate in alcohol-dependent individuals. Methods: Adult women (n = 10) and men (n = 40) with a diagnosis of alcohol-dependence were recruited from two Swedish 12-step treatment units for alcoholism. Subjects were genotyped for the TaqIA polymorphism. On average, 11/2 year after the end of the treatment program, subjects were re-interviewed by using the alcohol-related items from the Addiction Severity Index follow-up version. Results: Thirty-three (66%) subjects self-reported relapse and 17 (34%) abstinence during the follow-up period. Thirty-sex percent (18/50) were carriers of the A1 allele of the DRD2 gene region, and 64% (32/50) were non-carriers. Among the carriers of the A1 allele, 89% (16/18) reported relapse in contrast to 53% (17/32) in the non-carriers (P = 0.01; odds ratio = 7.1). Conclusion: The present study is, to our knowledge, the first report of an association between the TaqI A1 allele and a substantially increased relapse rate. It should be emphasized that the number of subjects is relatively small, and this investigation should therefore be considered as a pilot study. © The Author 2011. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved.
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| 2. |
- Malmberg, Kerstin, et al.
(author)
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Psychiatric problems associated with subthreshold ADHD and disruptive behaviour diagnoses in teenagers
- 2011
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:11, s. 1468-1475
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Journal article (peer-reviewed)abstract
- Aim: To study the coexistence of subthreshold diagnoses of both attention deficit hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBD) with other symptoms of child and adolescent psychiatric disorders as well as risk behaviours associated with smoking, alcohol and drug use. Methods: A population-based sample of twins including 177 girls and 135 boys was interviewed using the Swedish version of Kiddie-SADS Present and Lifetime Version (K-SADS-PL). Subthreshold diagnoses were compiled based on the ADHD and DBD criteria, where each criterion was assessed as 'possible' or 'certain' according to K-SADS-PL. The odds ratios (OR) between the subthreshold diagnoses and each of the screening questions in K-SADS-PL were calculated. Results: Subthreshold diagnoses of ADHD and DBD coexisted with the screening questions concerning depression, mania, panic attack, phobias, anorexia nervosa, motor tics and posttraumatic stress disorder (PTSD) in girls. In boys, these subthreshold diagnoses coexisted with symptoms of depression and PTSD. For both boys and girls, smoking and high alcohol consumption contributed to a high OR with regard to ADHD and DBD. Conclusion: Subthreshold diagnoses of ADHD and DBD were risk factors for several other psychiatric symptoms as well as smoking and high alcohol consumption. Thus, a broad clinical assessment is needed for adolescents with such preliminary diagnoses.
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| 3. |
- Wargelius, Hanna-Linn, et al.
(author)
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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
- 2012
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In: Psychiatric Genetics. - 0955-8829 .- 1473-5873. ; 22:1, s. 42-45
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Wargelius, Hanna-Linn, et al.
(author)
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Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.
- 2010
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In: Upsala journal of medical sciences. - : Uppsala Medical Society. - 2000-1967 .- 0300-9734. ; 115:1, s. 49-55
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Journal article (peer-reviewed)abstract
- Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.
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| 5. |
- Wargelius, Hanna-Linn
(author)
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The Relation between Serotonergic Biomarkers and Behaviour : – studies on human primates, non-human primates and transgenic mice
- 2011
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Doctoral thesis (other academic/artistic)abstract
- 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.
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