ItemADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes(2022) Kanarik, Margus; Grimm, Oliver; Mota, Nina Roth; Reif, Andreas; Harro, JaanusADHD is a major burden in adulthood, where co-morbid conditions such as depression, substance use disorder and obesity often dominate the clinical picture. ADHD has substantial shared heritability with other mental disorders, contributing to comorbidity. However, environmental risk factors exist but their interaction with genetic makeup, especially in relation to comorbid disorders, remains elusive. This review for the first time summarizes present knowledge on gene x environment (GxE) interactions regarding the dopamine system. Hitherto, mainly candidate (GxE) studies were performed, focusing on the genes DRD4, DAT1 and MAOA. Some evidence suggest that the DRD4 exon 3 variable number tandem repeat (VNTR) and MAOA uVNTR may mediate (GxE) interactions in ADHD generally, and comorbid conditions specifically. For other polymorphisms, evidence is contradictory and less convincing. Particularly lacking are longitudinal studies testing the interaction of well-defined environmental with polygenic risk scores reflecting the dopamine system in its entirety. Only such an approach would be less susceptible to false-positive findings and provide clues on how genes could interact with non-genetic factors to shape psychopathology over the life span. ItemRisk-taking in traffic is associated with unhealthy lifestyle: Contribution of aggressiveness and the serotonin transporter genotype(2022) Tokko, Tõnis; Eensoo, Diva; Luht-Kallas, Kadi; Harro, JaanusObjectives: Risk taking behaviour, including in traffic, is related to impulsivity and aggressiveness, and so is unhealthy lifestyle. The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been associated with impulsivity, aggression, alcohol use, speed limit exceeding and traffic accidents. The aim of this study was to examine whether subjects with less healthy eating and exercise habits take more risks in traffic, and whether impulsivity, aggressiveness and the serotonin transporter genotype could mediate or moderate any such associations. Method: A sub-sample of the Estonian Psychobiological Study of Traffic Behaviour (EPSTB (n = 817) with mean age (SD) = 31.4 (10.0) years filled out lifestyle questionnaires. Impulsivity was measured by Adaptive and Maladaptive Impulsivity Scale and aggressiveness by Buss – Perry Aggression Questionnaire. Traffic violation data in the previous 5 years period were obtained from police database. Results: Speed limit exceeders had higher physical and verbal aggression, higher AUDIT scores, they reported more vigorous physical activity and drinking energy drinks more often. Path analysis showed that higher AUDIT scores were associated with speeding via higher physical aggression. 5-HTTLPR was not directly associated with speeding or driving while impaired by alcohol (DWI), but 5-HTTLPR s’-allele carriers had lower AUDIT scores if they were not junk food eaters and the other way around, while l’/l’ homozygosity was associated with DWI via higher AUDIT scores. Conclusion: Significant associations exist between risky traffic behaviour and aspects of lifestyle such as consumption of alcohol or junk food or energy drinks, as well as engagement in vigorous physical activity, while traits such as aggressiveness and the variation in the serotonergic system appear as mediating and moderating factors. Interventions preventing 3 accidents should focus on wider array of behaviours and use personalised approach. Genetic variation should be investigated regarding associations with risk taking and health behaviour, and response to interventions. ItemAssociation of Impulsivity With Food, Nutrients, and Fitness in a Longitudinal Birth Cohort Study(2022) Matrov, Denis; Kurrikoff, Triin; Villa, Inga; Sakala, Katre; Pulver, Aleksander; Veidebaum, Toomas; Shimmo, Ruth; Harro, JaanusBackground: Impulsivity is a psychiatric vulnerability factor strongly associated with substance abuse but also with unhealthy diet. Whether these associations extend to specific nutrients is largely unknown. Therefore, we investigated the longitudinal association between diet, cardiorespiratory fitness, and 2 impulsivity dimensions in a representative sample of south Estonian adolescents and young adults. Impulsivity and dietary intake were measured 3 times in 2 birth cohorts at regular intervals in individuals aged 15 to 33 years. Methods: The sample included 2 birth cohorts of the longitudinal Estonian Children Personality Behaviour and Health Study. The analytic sample size consisted of 2883 observations (56.4% females). The primary outcomes were adaptive and maladaptive impulsivity scores measured by an original 24-item Likert-type questionnaire. Impulsivity scores were predicted from the food diaries data converted into nutrient categories. A linear mixed-effects approach was used to model the time dependence between observations. Results: Lower maladaptive impulsivity was associated with higher cardiorespiratory fitness (β = −.07; 95% CI = −0.12; −0.03). Higher maladaptive impulsivity was associated with lower dietary intake of zinc (β = −.10; −0.15; −0.06) and vegetables (β = −.04; −0.07; −0.01) and higher intake of sodium (β = .06; 0.02; 0.10). Vitamin B6 was positively associated with adaptive impulsivity (β = .04; 0.01; 0.07). Additionally, some of the adjusted models showed significant but weak associations with selenium, alcohol, fish, and cereal products. Conclusions: Food choice may affect the neurochemistry and therefore regulate the manifestations of impulsivity. We identified associations between several (micro)nutrients and maladaptive impulsivity. ItemIs low platelet MAO activity associated with antisocial behavior? Evidence from representative samples of longitudinally observed birth cohorts(2023) Sakala, Katre; Katus, Urmeli; Kiive, Evelyn; Veidebaum, Toomas; Harro, JaanusLower platelet monoamine oxidase (MAO) activity has been associated with problem behaviors, including criminal behavior, but not all studies agree. We have examined platelet MAO activity and antisocial behavior involving police contact in a longitudinal birth cohort study. The sample included both birth cohorts (original n = 1238) of the Estonian Children Personality Behavior and Health Study. Platelet MAO activity was measured at ages 15, 18 and 25 radioenzymatically with ß-phenylethylamine as the substrate. Police contacts were self-reported in an interview and drug use in a questionnaire filled in during a laboratory visit. In cross-sectional analyses, males with the record of antisocial behavior had lower platelet MAO activity. In longitudinal mixed-effect regression models, this association was found to be independent of smoking. Furthermore, including smoking in the model revealed lower platelet MAO activity also in females with past antisocial behaviour. A further exploratory regression analysis with antisocial behavior at two levels of frequency and consideration of self-reported use of illicit drugs either in a single occasion or repeatedly demonstrated some "dose-dependency" in the relationship of antisocial behavior and platelet MAO activity. Platelet MAO activity was lower in male but not female subjects with basic education level as compared to secondary and higher education, but it was not related to non-verbal intelligence. Neither was platelet MAO activity associated with socio- economic status. In conclusion, antisocial behavior as occurring in general population is associated with low platelet MAO activity that probably reflects low capacity of the serotonergic system. ItemAssociation between platelet MAO activity and lifetime drug use in a longitudinal birth cohort study(2022) Sakala, Katre; Kasearu, Kairi; Katus, Urmeli; Veidebaum, Toomas; Harro, JaanusRationale: Platelet monoamine oxidase (MAO) activity, a marker of central serotonergic capacity, has been associated with a variety of problem behaviours. However, studies on platelet MAO activity and addictive drugs has not been consistently linked with addiction or found to predict illicit substance use initiation or frequency. Objectives: Platelet MAO activity and illicit drug use was examined in a longitudinal birth cohort study. Methods: The sample included both birth cohorts (original n = 1238) of the Estonian Children Personality Behaviour and Health Study. Longitudinal association from age 15 to 25 years between platelet MAO activity and lifetime drug use was analyzed by mixed-effects regression models. Differences at ages 15, 18 and 25 were analyzed by t-test. Cox proportional hazard regression analysis was used to assess the association between platelet MAO activity and the age of drug use initiation. Results: Male subjects who reported at least one drug use event had lower platelet MAO activity compared to nonusers, both in cross-sectional and longitudinal analysis. Males with low platelet MAO activity had started to use drugs at a younger age. Moreover, in male subjects who had experimented with illicit drugs only once in lifetime, low platelet MAO activity was also associated with higher risk at a younger age. In females, platelet MAO activity was not associated with drug use. Conclusion: In males, low platelet MAO activity is associated with drug abuse primarily owing to risk taking at early age. ItemCholecystokinin B receptor gene polymorphism (rs2941026) is associated with anxious personality and suicidal thoughts in a longitudinal study(2022) Lvovs, Aneth; Matrov, Denis; Kurrikoff, Triin; Veidebaum, Toomas; Harro, JaanusObjectives: Cholecystokinin is a neuropeptide with a role in the neurobiology of adaptive behaviour that is implicated in anxiety disorders, while the underlying mechanisms currently remain insufficiently explained. The rs2941026 variation in the cholecystokinin B receptor gene has previously been associated with trait anxiety. Our aim was to investigate associations between the CCKB receptor gene polymorphism rs2941026 with anxiety, personality, depressiveness and suicidality in a longitudinal study of late adolescence and early adulthood. Methods: We used reports on trait and state anxiety, depressiveness and suicidal thoughts, as well as Affective Neuroscience Personality Scales, from the two birth cohorts of the Estonian Children Personality, Behaviour and Health Study. We measured associations between the CCKBR gene rs2941026 and anxiety-related phenotypes both longitudinally and cross-sectionally at ages 15, 18, 25 and 33. Results: Homozygosity for both alleles of the CCKBR rs2941026 was associated with higher trait and state anxiety in the longitudinal analysis. Cross-sectional comparisons were statistically significant at ages 18 and 25 for trait anxiety and at ages 25 and 33 for state anxiety. Higher depressiveness and suicidal thoughts were associated with the A/A genotype at age 18. Additionally, homozygosity for the A-allele was related to higher FEAR and SADNESS in the Affective Neuroscience Personality Scales. The genotype effects were more apparent in females, who displayed higher levels of negative affect overall. Conclusions: CCKBR genotype is persistently associated with negative affect in adolescence and young adulthood. The association of the CCKBR rs2941026 genotype with anxiety-related phenotypes is more pronounced in females. ItemDriving risks of young drivers with symptoms of attention deficit hyperactivity disorder: association with the dopamine transporter gene VNTR polymorphism(2022) Tokko, Tõnis; Eensoo, Diva; Miškinyte, Grete; Harro, JaanusBackground: Road traffic injuries are a leading cause of death for young adults, and young drivers with higher expression of symptoms of attention deficit-hyperactivity disorder (ADHD) could pose an even greater risk in traffic. Dopaminergic dysfunction has been found to occur in ADHD, with the dopamine transporter (DAT) gene VNTR polymorphism (DAT1 VNTR; rs28363170) being one of the most consistent genetic markers. Thus, we aimed at clarifying how the ADHD symptoms and the DAT1 VNTR relate to risk-taking behaviour in traffic, impulsivity and driving anger in young drivers. Method: We used data of two traffic behaviour study samples (n = 741, mean age = 23.3±7.2 years; n = 995, mean age = 22.9±8.1 years) and the Estonian Children Personality Behaviour and Health Study (ECPBHS; traffic behaviour data n = 1016, mean age = 25.2±2.1 years). ADHD symptoms were assessed by self-report with the Adult ADHD Self-Report Scale (ASRS v1.1) and impulsivity with the Adaptive and Maladaptive Impulsivity Scale. Traffic behavioural measures were either self-reported (Driver Behaviour Questionnaire, Driving Anger Scale) or obtained from databases (registered accidents and violations). Results: Drivers with more self-reported ADHD symptoms also reported more risk-taking in traffic and had more of recorded traffic accidents and violations. DAT1 9R carriers had a higher probability of high traffic risk behaviour only if they also had ADHD symptoms. Conclusion: Higher level of ADHD symptoms is a significant risk factor in traffic, and carrying of the DAT1 9R allele appears to aggravate these risks. ItemDriving risks of young drivers with symptoms of attention deficit hyperactivity disorder: association with the dopamine transporter gene VNTR polymorphism(2022) Tokko, Tõnis; Eensoo, Diva; Miškinyte, Grete; Harro, JaanusRoad traffic injuries are a leading cause of death for young adults, and young drivers with higher expression of symptoms of attention deficit-hyperactivity disorder (ADHD) could pose an even greater risk in traffic. Dopaminergic dysfunction has been found to occur in ADHD, with the dopamine transporter (DAT) gene VNTR polymorphism (DAT1 VNTR; rs28363170) being one of the most consistent genetic markers. Thus, we aimed at clarifying how the ADHD symptoms and the DAT1 VNTR relate to risk-taking behaviour in traffic, impulsivity and driving anger in young drivers. We used data of two traffic behaviour study samples (n = 741, mean age = 23.3±7.2 years; n = 995, mean age = 22.9±8.1 years) and the Estonian Children Personality Behaviour and Health Study (ECPBHS; traffic behaviour data n = 1016, mean age = 25.2±2.1 years). ADHD symptoms were assessed by self-report with the Adult ADHD Self-Report Scale (ASRS v1.1) and impulsivity with the Adaptive and Maladaptive Impulsivity Scale. Traffic behavioural measures were either self-reported (Driver Behaviour Questionnaire, Driving Anger Scale) or obtained from databases (registered accidents and violations). Drivers with more self-reported ADHD symptoms also reported more risk-taking in traffic and had more of recorded traffic accidents and violations. DAT1 9R carriers had a higher probability of high traffic risk behaviour only if they also had ADHD symptoms. Conclusion Higher level of ADHD symptoms is a significant risk factor in traffic, and carrying of the DAT1 9R allele appears to aggravate these risks. ItemVariation rs6971 in the Translocator Protein Gene (TSPO) Is Associated with Aggressiveness and Impulsivity but Not with Anxiety in a Population-Representative Sample of Young Adults(2021) Vaht, MariliisExpression of the 18-kDa translocator protein (TSPO), originally identified as a peripheral benzodiazepine receptor, has been found to be altered in several psychiatric disorders. A common single nucleotide polymorphism (rs6971) in the TSPO gene leads to an amino acid substitution, Ala147Thr, which dramatically alters the affinity with which TSPO binds drug ligands. As cholesterol also binds TSPO in the same transmembrane domain, it is suggested that this substitution may impair the ability of TSPO to bind or import cholesterol, and hence may affect steroid synthesis and hypothalamic-pituitary-adrenal function. The analysis was carried out on older birth cohort (n = 655) of the longitudinal Estonian Children Personality, Behavior and Health Study sample. Anxiety, aggressive behavior, impulsiveness, and history of stressful life events were self-reported in various data collection waves. Psychiatric assessment of lifetime prevalence of anxiety disorders was carried out at 25 years of age by experienced clinical psychologists. TSPO rs6971 was genotyped in all participants. TSPO rs6971 was not associated with self-reported levels of anxiety or lifetime prevalence of anxiety disorders. However, participants homozygous for the minor A allele displayed the highest aggressiveness and dysfunctional impulsivity scores. The positive, adaptive aspect of impulsivity was sensitive to stressful life events, as the AA genotype was associated with functional impulsivity only when the participants had experienced a low number of stressful life events during childhood. TSPO rs6971 polymorphism may be related to development of aggressiveness and impulsivity by adulthood, regardless of the participants’ gender. ItemInteractive effects of DRD2 rs6277 polymorphism, environment and sex on impulsivity in a population-representative study(Elsevier, 2021-04) Klaus, K.; Vaht, M.; Pennington, K.; Harro, J.Previous research has shown that dopaminergic dysregulation and early life stress interact to impact on aspects of impulse control. This study aimed to explore the potentially interactive effects of the rs6277 polymorphism of the dopamine D2 receptor gene (DRD2), stressful or supportive environment and sex on behavioural and self-reported measures of impulsivity, as well as alcohol use – a condition characterised by a deficit in impulse control. The sample consisted of the younger cohort (n=583) of the longitudinal Estonian Children Personality, Behaviour and Health Study. The results showed that the CC homozygotes (suggested to have decreased striatal D2 receptor availability) who had experienced stressful life events (SLE) or maltreatment in the family prior to age 15 showed higher self-reported maladaptive impulsivity at age 15. The genotype-SLE interaction and further association with sex was also evident in the frequency of alcohol use at age 15. Lack of warmth in the family contributed to significantly higher levels of thoughtlessness and more frequent alcohol use in CC carriers at age 25, whereas family support was associated with lower thoughtlessness scores in CC males, which may suggest a protective effect of supportive family environment in this group. Together the findings suggest that DRD2 rs6277 polymorphism, in interaction with environmental factors experienced in childhood and youth may affect facets of impulsivity. Future work should aim to further clarify the sex and age-specific effects of stressful and supportive environment on the development of neuronal systems that are compromised in disorders characterised by deficits in impulse control. ItemVariants of the aggression-related RBFOX1 gene in a population representative birth cohort study: aggressiveness, personality and alcohol use disorder(2020) Vaht, Mariliis; Laas, Kariina; Fernàndez-Castillo, Noèlia; Kurrikoff, Triin; Kanarik, Margus; Faraone, Stephen V.; Tooding, Liina-Mai; Veidebaum, Toomas; Franke, Barbara; Reif, Andreas; Cormand, Bru; Harro, JaanusBackground Recently RBFOX1, a gene encoding an RNA binding protein, has consistently been associated with aggressive and antisocial behaviour. Several loci in the gene have been nominally associated with aggression in genome-wide association studies; the risk alleles being more frequent in general population. We have hence examined the association of four RBFOX1 single nucleotide polymorphisms, previously found related to aggressive traits, with aggressiveness, personality, and alcohol use disorder in birth cohort representative samples. Methods We used both birth cohorts of the Estonian Children Personality Behaviour and Health Study (ECPBHS; original n=1,238). Aggressiveness was assessed using the Buss-Perry Aggression Questionnaire and the Lifetime History of Aggressiveness structured interview at age 25 (younger cohort) or 33 (older cohort). Big Five personality at age 25 was measured with self reports and the lifetime occurrence of alcohol use disorder assessed with the MINI interview. RBFOX1 polymorphisms rs809682, rs8062784, rs12921846 and rs6500744 were genotyped in all participants. Given the restricted size of the sample, correction for multiple comparisons was not applied. Results Aggressiveness was not significantly associated with RBFOX1 genotype. RBFOX1 rs8062784 was associated with neuroticism and rs809682 with extraversion. Two out of four analyzed RBFOX1 variants, rs8062784, and rs12921846, were associated with occurrence of alcohol use disorder. Conclusions In the birth cohort representative sample of the ECPBHS, no association of RBFOX1 with aggressiveness was found, but RBFOX1 variants affected basic personality traits and the prevalence of alcohol use disorder. Future studies on RBFOX1 should consider the moderating role of personality and alcohol use patterns in aggressiveness. ItemNeuropeptide Y gene variants in obesity, dietary intake, blood pressure, lipid and glucose metabolism: a longitudinal birth cohort study(Elsevier, 2021) Katus, Urmeli; Villa, Inga; Ringmets, Inge; Veidebaum, Toomas; Harro, JaanusObjective: Neuropeptide Y affects several physiological functions, notably appetite regulation. We analysed the association between four single nucleotide polymorphisms (SNP) in the NPY gene (rs5574, rs16147, rs16139, rs17149106) and measures of obesity, dietary intake, physical activity, blood pressure, glucose and lipid metabolism from adolescence to young adulthood. Methods: The sample included both birth cohorts of the Estonian Children Personality Behaviour and Health Study at ages 15 (n = 1075 with available complete data), 18 (n = 913) and 25 (n = 926) years. Linear mixed-effects regression models were used for longitudinal association between NPY SNP-s and variables of interest. Associations at ages 15, 18 and 25 were analysed by ANOVA. Results: Rs5574 CC-homozygotes had a greater increase per year in waist-to-hip ratio (WHR) and a smaller decrease in daily energy intake and carbohydrate intake from age 15 to 25 years; fasting glucose and cholesterol were higher in rs5574 CC-homozygotes. Rs16147 TT homozygotes had higher body weight and a greater increase in sum of 5 skinfolds, waist circumference, WHR and waist-to-height ratio; however, they had lower carbohydrate intake throughout the observation period. Rs16147 TT-homozygotes and both rs16139 and rs17149106 heterozygotes had higher triglyceride levels. All NPY SNP-s were associated with blood pressure: rs5574 TT-and rs16147 CC-homozygotes had a smaller increase in diastolic blood pressure, while rs16139 and rs17149106 heterozygous had lower blood pressure throughout the study. Conclusion: Variants of the NPY gene were associated with measures of obesity, dietary intake, glucose and lipid metabolism and blood pressure from adolescence to young adulthood. ItemThe role of reward sensitivity in obesity and its association with Transcription Factor AP2B: a longitudinal birth cohort study(Elsevier, 2020) Katus, Urmeli; Villa, Inga; Ringmets, Inge; Pulver, Aleksander; Veidebaum, Toomas; Harro, JaanusObjective One factor potentially contributing to obesity is reward sensitivity. We investigated the association between reward sensitivity and measures of obesity from 9–33 years of age, paying attention to the inner structure of reward sensitivity. Methods The sample included both birth cohorts (originally n = 1176) of the Estonian Children Personality Behaviour and Health Study. The association between reward sensitivity and measures of obesity was assessed using mixed-effects regression models. Associations at ages 9 (younger cohort only), 15, 18, 25 and 33 (older cohort) years were analyzed by one-way ANOVA. The indirect effect of the gene encoding transcription factor 2 beta (TFAP2B) on obesity through reward sensitivity was tested using mediation analysis. Results According to linear mixed effects regression models, an increase in scores of Insatiability by Reward and both of its components, Excessive Spending and Giving in to Cravings, significantly increased body weight, body mass index, sum of five skinfolds, waist circumference, hip circumference and waist-to-height ratio from 15 to 25 years of age. Findings were similar at age 9 and 33 years. In contrast, no association between obesity and Openness to Rewards or its facets was observed. The TFAP2B genotype was also associated with fixation to rewards in females, but not with striving towards reward multiplicity. Conclusion Our results suggest that reward sensitivity is associated with obesity by its reward fixation component. The heterogeneity of the reward sensitivity construct should be taken into account in studies on body composition. ItemReward sensitivity, affective neuroscience personality, symptoms of attentiondeficit/hyperactivity disorder, and TPH2-703G/T (rs4570625) genotype(Cambridge University Press, 2020) Pulver, Aleksander; Kiive, Evelyn; Harro, JaanusObjective: Reward sensitivity is an increasingly used construct in psychiatry, yet its possible inner structure and relationship with other affective variables are not well known. Methods: A reward sensitivity measurement scale was constructed on the basis of large item pool collected from birth cohort representative samples (the Estonian Children Personality Behaviour and Health Study; original n = 1238). Affective Neuroscience Personality Scale (ANPS) and the Adult Attention deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS) were administered in young adulthood. A variant (rs4570625) of the gene encoding tryptophan hydroxylase 2 (TPH2) that is responsible for the synthesis of central serotonin was genotyped. Results: Reward sensitivity consisted of two orthogonal components, operationally defined as Openness to Rewards and Insatiability by Reward, that respectively characterise the striving towards multiple rewards and the strong pursuit and fixation to a particular reward. While SEEKING and PLAY (and to lower extent CARE) of the ANPS co-varied with Openness to Rewards, FEAR, SADNESS, and ANGER were related to Insatiability by Reward. The total score of ASRS was moderately correlated with Insatiability by Reward, while the association with Openness to Rewards was negligible. However, ASRS Inattention had some negative relationship with the Social Experience facet of Openness to Rewards. The T/T homozygotes for the TPH2 promoter polymorphism had lower Insatiability by Reward but not Openness to Rewards. Conclusions: Behaviours sensitive to rewards are separable to the components of variability and fixation, and these components are differentially related to affective aspects of personality, attention, and hyperactivity as well as to TPH2 genotype. ItemAssociation of FTO rs1421085 with obesity, diet, physical activity and socioeconomic status: a longitudinal birth cohort study(2020) Katus, Urmeli; Villa, Inga; Ringmets, Inge; Vaht, Mariliis; Mäestu, Evelin; Mäestu, Jarek; Veidebaum, Toomas; Harro, JaanusBackground and aims Fat mass and obesity-associated protein (FTO) variants are among genetic variants frequently associated with obesity. We analyzed the association between FTO rs1421085 polymorphism and obesity, dietary intake, cardiorespiratory fitness (CRF), physical activity, and socioeconomic status (SES) from the age of 9–25 years. Methods and results The sample included both birth cohorts (originally n = 1176) of the Estonian Children Personality Behaviour and Health Study. The association between FTO rs1421085 and obesity, dietary intake, CRF, physical activity, and SES from the age of 15–25 years was assessed using linear mixed-effects regression models. Associations at ages 9 (younger cohort only), 15, 18, and 25 years were assessed by one-way ANOVA. Male C-allele carriers had significantly (p < 0.05) higher body mass index (BMI), sum of 5 skinfolds, body fat percentage, and hip circumference from the age of 15–25 years. Findings were similar at the age of 9 years. In female subjects, waist-to-hip ratio was significantly greater in CC homozygotes. Interestingly, female CC homozygotes had a greater decrease in the rate of change in daily energy intake and lipid intake per year and higher physical activity score at every fixed time point. Moreover, in females, an effect of FTO × SES interaction on measures of obesity was observed. Conclusion The FTO rs1421085 polymorphism was associated with obesity and abdominal obesity from childhood to young adulthood in males, and with abdominal obesity from adolescence to young adulthood in females. This association is rather related to differences in adipocyte energy metabolism than lifestyle. ItemLow cholesterol levels in children predict impulsivity in young adulthood(2019) Tomson-Johanson, Katrin; Kaart, Tanel; Kiivet, Raul-Allan; Veidebaum, Toomas; Harro, JaanusObjective: Severe behavioural issues such as impulsive action and suicide have since long been associated with low levels of cholesterol. While it is known that cholesterol plays a role in neural development and hence low levels of serum lipids could have long-term effects on behaviour, there are no longitudinal studies showing association of serum lipids levels with impulsivity. We aimed to examine the prognostic properties of serum lipid levels during childhood and adolescence on measures of impulsivity during early adulthood in a representative birth cohort sample. Methods: We have investigated whether serum lipid levels measured at 9, 15, 18 and 25 years of age have an association with impulsivity in 25 years old young adults. This analysis was based on data of the birth cohort representative samples of the Estonian Children Personality Behaviour and Health Study (original n=1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale. Results: Total and LDL cholesterol measured in 9, 15 and 18 years old boys predicted Disinhibition and Thoughtlessness in 25 years old young adults. High scores of Disinhibition were associated with low total and LDL cholesterol levels in males but, while less consistently, with high total and LDL cholesterol levels in females. Cross-sectional analysis did not result in systematic outcomes. Conclusions: Serum lipid levels could have an impact on development of maladaptive impulsivity starting from an early age. This effect of cholesterol continues throughout adolescence into young adulthood. ItemOrexin/hypocretin receptor gene (HCRTR1) variation is associated with aggressive behaviour(ScienceDirect, 2019-09) Harro, Jaanus; Laas, Kariina; Eensoo, Diva; Kurrikoff, Triin; Sakala, Katre; Vaht, Mariliis; Parik, Jüri; Mäestu, Jarek; Veidebaum, ToomasOrexins, alternatively called hypocretins, are neuropeptides with crucial role in maintaining wakefulness. The orexin system is thought to mediate a coordinated defense response but thus far investigated from the flight, but never fight, response perspective. An HCRTR1 gene variant (rs2271933 G > A) leading to amino acid substitution (Ile408Val) has been associated with migraine and mood disorders. We genotyped, and assessed aggressive behaviour in both birth cohorts (n = 655 and 583) of the Estonian Children Personality Behaviour and Health Study (ECPBHS). Measures of aggressiveness were collected at age 25 or 33 and data on stressful life events (SLE-s) at age 15. Violations of traffic law were monitored in the samples of the Estonian Psychobiological Study of Traffic Behaviour. In both birth cohorts of the ECPBHS, the HCRTR1 the A/A homozygotes reported higher aggression in both Buss-Perry Aggression Questionnaire and the Life History of Aggression Interview. With either measure of aggressiveness, the HCRTR1 genotype effect was dependent on experience of SLE, the highest level of aggressiveness increase by environment being found in female A/A homozygotes. The HCRTR1 A/A homozygotes scored higher in the ANGER facet of the Affective Neuroscience Personality Scale, while such an effect on FEAR was found only in females. Male HCRTR1 A/A homozygotes were more likely to relapse into drunk driving of a passenger car, and in two independent samples the A-allele carriers were causing traffic accidents more often. Conclusively, self-report, interview, and traffic record data converge indicating that the HCRTR1 Ile408Val genotype is associated with aggressiveness and breach of law. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’. ItemEfficacy of intervention at traffic schools reducing impulsive action, and association with candidate gene variants(Acta Neuropsychiatrica, 2019) Luht, Kadi; Tokko, Tõnis; Eensoo, Diva; Vaht, Mariliis; Harro, JaanusOBJECTIVE: Road traffic injuries are the leading cause of death among young people. Recognition of the contribution of impulsive behaviour may help novice drivers to behave more safely. Previously a brief intervention focusing on impulsive traffic behaviour conducted by psychologists in driving schools had been effective. The aim of this study was an independent re-evaluation of the effect of the intervention, as conducted by driving school teachers, and assessment of the potential associations with candidate genotypes. METHODS: Driving school students (mean age 22.5, SD=7.9) were divided into intervention (n=704) and control (n=737) groups. Driving school teachers were trained to administer the intervention which consisted of a lecture and group work (1.5 h in total) on impulsivity. Traffic offences and crashes were monitored during 3 years, using police and traffic insurance fund databases. Functional polymorphisms of the dopamine transporter (DAT) and serotonin transporter genes (DAT1 VNTR and 5-HTTLPR) were assessed. RESULTS: The intervention significantly lowered general traffic risk and prevalence of traffic accidents. DAT1 VNTR 9R carriers, particularly males, had higher general traffic risk in the whole sample. Female 5-HTTLPR s' allele carriers of the intervention group had the lowest general traffic risk. Intervention was most effective in female DAT1 VNTR 10R/10R homozygotes. CONCLUSIONS: Brief impulsivity-centred intervention appears as a promising strategy for preventing risk-taking behaviour in novice drivers and can be fully integrated to driving school curriculum. ItemFamily environment interacts with CRHR1 rs17689918 to predict mental health and behavioral outcomes(2018) Roy, Arunima; Laas, Kariina; Kurrikoff, Triin; Reif, Andreas; Veidebaum, Toomas; Lesch, Klaus-Peter; Harro, Jaanus ItemRelapse of drunk driving and association with traffic accidents, alcohol-related problems, and biomarkers of impulsivity(Cambridge University Press, 2018) Tokko, Tõnis; Eensoo, Diva; Vaht, Mariliis; Lesch, Klaus-Peter; Reif, Andreas; Harro, JaanusObjective: Individual biological predispositions should play a role in risky driving behaviour. Platelet monoamine oxidase (MAO) activity, dopamine transporter gene (DAT1) and neuropeptide S receptor 1 (NPSR1) gene polymorphisms have been identified as markers of impulsivity, alcohol use and excessive risk-taking. We aimed to find out how this knowledge on neurobiology of impulsivity applies to drunk driving and traffic behaviour in general. Methods: We have longitudinally examined the behaviour of drunk drivers (n=203) and controls (n=211) in traffic, in association with their alcohol-related problems, personality measures and the three biomarkers. We analysed differences between the subjects based on whether they had committed driving while impaired by alcohol (DWI) violation in a 10-year time period after recruitment or not and investigated further, what kind of predictive value do the different biomarkers have in committing DWI and other traffic violations and accidents. Results: The original drunk drivers group had lower platelet MAO activity but further DWI was not significantly associated with this measure. Being a NPSR1 T-allele carrier contributed to the risk of repeatedly committing DWI. DAT1 9R carriers in contrast were involved in more traffic accidents by their own fault (active accidents), compared to 10R homozygotes in the whole sample. All groups with DWI also had significantly more alcohol-related problems and higher scores in maladaptive impulsivity compared to controls without DWI. Conclusions: Established biological markers of alcohol use and impulsivity can be reliably associated with everyday traffic behaviour and help in contributing to the understanding of the need for more personalized prevention activities.