Hanna-Linn Wargelius

Adolescent girls and criminal activity : role of MAOA-LPR genotype and psychosocial factors.

Recent findings among boys show that interactions between a polymorphism in the monoamine oxidase A gene promoter region (MAOA‐LPR) and psychosocial factors predict criminal activity. The objective of this study was to investigate whether this finding could be extended to adolescent girls. One hundred nineteen female adolescents were recruited among respondents to a cross‐sectional study of the total population of 16‐ and 19‐year old girls. These girls constituted a randomly selected sub‐sample from groups representing different degrees of risk behavior. The subjects filled in a questionnaire and were interviewed and genotyped with regard to MAOA‐LPR. The results indicate that the long, (4‐repeat) allele confer an increased risk for criminal behavior in the presence of psychosocial risk. Among girls without social risk, MAOA‐LPR genotype was of no importance for criminal behavior. The present results suggest that previous observations on adolescent males, which demonstrate that the short MAOA‐LPR genotype and psychosocial adversity interact to predict criminal activity, may not be applicable to females.

ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

BackgroundPharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorder (DBD). We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B) activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR) and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR).MethodsA population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes.ResultsWe found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD). In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD). In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior.ConclusionOur study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.

Do Alcohol-dependent Individuals with DRD2 A1 Allele Have an Increased Risk of Relapse? A Pilot Study

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, 1½ 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.

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

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.

Psychiatric problems associated with subthreshold ADHD and disruptive behaviour diagnoses in teenagers

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.

Associations of MAOA-VNTR or 5HTT-LPR alleles with attention-deficit hyperactivity disorder symptoms are moderated by platelet monoamine oxidase B activity

The monoamine systems have been suggested to play a role in the biological basis of attention-deficit hyperactivity disorder (ADHD) symptoms. Thus, polymorphisms, for example, in the monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) genes have been associated with ADHD-like phenotypes. Furthermore, platelet monoamine oxidase B (MAOB) activity has frequently been linked to impulsiveness-related traits. In this study, we have studied ADHD symptoms with regard to the combination of platelet MAOB activity and MAOA-variable number of tandem repeats (VNTR) or 5HTT-LPR genotype. The study group consisted of 156 adolescent twin pairs, that is, 312 individuals, who participated in a previous study. ADHD symptoms were scored with a structured clinical interview of both the twins and a parent using Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. The 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 and 0.01, respectively). This re-examination of ADHD scores in a nonclinical sample suggests that effects of MAOA-VNTR and 5HTT-LPR are moderated by platelet MAOB activity.

Electrophysiological and behavioral correlates of polymorphisms in the transcription factor AP-2β coding gene

Transcription factor AP-2beta may influence brain monoaminergic systems by regulating target genes. Several monoaminergic genes, including the serotonin transporter gene, have AP-2beta binding sites. Late auditory-evoked potentials (P1, N1/P2) and impulsiveness-related personality traits are correlated, and both are modulated by monoaminergic neurotransmission. The present study assesses the impact of two AP-2beta polymorphisms (VNTRs within intron 1 and 2) together with the serotonin transporter polymorphism 5-HTTLPR on late auditory-evoked potentials and personality for the first time. EEG was recorded from 91 male subjects at central electrode positions while tones of six intensity levels were presented. Additionally, subjects completed personality questionnaires. Both AP-2beta polymorphisms revealed significant main effects on P1, and haplotype analysis confirmed the contribution of both AP-2beta-polymorphisms. Additionally, AP-2beta and 5-HTTLPR showed interactions with respect to P1. 5-HTTLPR revealed a main effect on N1/P2 but not P1. Impulsiveness showed an association with intron 1 VNTR. The results are discussed with respect to differential impact of AP-2beta polymorphisms and 5-HTTLPR on the monoaminergic systems. The findings promote replication in a larger sample and suggest a potential usefulness of AP-2beta polymorphisms in explaining or predicting central nervous diseases, drug effects and side effects.

Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys

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.

P01-364 Associations of 5HTT-LPR with ADHD symptoms are moderated by platelet MAOB activity

Introduction The monoamine systems have been suggested to play a role for the biological background of ADHD symptoms. Thus, polymorphisms in e.g. the serotonin transporter (5HTT) gene have been associated with ADHD like phenotypes. Furthermore, platelet MAOB activity has frequently been linked to impulsiveness-related traits. Objective Biological markers and candidate genes for psychiatric problems are often studied separately. We study ADHD symptoms with regard to the combination of platelet MAOB activity and 5HTT genotype. Aim To test the hypothesis that associations between ADHD like behavior problems and 5HTT-LPR polymorphism, would be more robust if calculations were done in combination with platelet MAOB enzyme activity. Methods The study group consisted of 156 adolescent twin pairs, i.e. 312 individuals. 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 (K-SADS-PL). Results Presence of a short 5HTT-LPR allele, in combination with high levels of platelet MAOB enzyme activity was associated with higher scores of ADHD like problems and disruptive behavior in boys. No such associations were found in girls. Conclusion This examination of ADHD scores in a non-clinical sample suggests that the effects of the 5HTT-LPR are moderated by platelet MAOB activity.