Browsing by Author "Harro, Jaanus"

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ADHD 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, Jaanus
ADHD 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.
Association between platelet MAO activity and lifetime drug use in a longitudinal birth cohort study
(2022) Sakala, Katre; Kasearu, Kairi; Katus, Urmeli; Veidebaum, Toomas; Harro, Jaanus
Rationale: 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.
Association 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, Jaanus
Background 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.
Association 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, Jaanus
Background: 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.
Association of orexin/hypocretin receptor gene (HCRTR1) with reward sensitivity, and interaction with gender
(Elsevier, 2020) Pulver, Aleksander; Kiive, Evelyn; Harro, Jaanus; Kanarik, Margus
Orexins/hypocretins maintain wakefulness, increase appetite and participate in the coordination of stress response. We have recently provided evidence on the role of orexins in aggression, showing the association of the HCRTR1 genotype. (rs2271933 G > A; leading to amino acid substitution Ile408Val) with aggressiveness or breach of law in four independent cohorts. Aggressive behaviour can be reward driven and hence we have examined the association of HCRTR1 rs2271933 genotype with different aspects of reward sensitivity in the birth cohort representative Estonian Children Personality Behaviour and Health Study. HCRTR1 genotype was associated with reward sensitivity in a gender dependent manner. Male HCRTR1 A/A homozygotes had higher Openness to Rewards and the overall reward sensitivity score while, in contrast, female A/A homozygotes scored lower than G-allele carriers in Openness to Rewards. In the total sample, aggressiveness correlated positively with reward sensitivity, but this was on account of Insatiability by Reward. In contrast, the HCRTR1 A/A homozygotes had a positive association of aggressiveness and Openness to Rewards. Experience of stressful life events had a small but significant increasing effect on both aspects of reward sensitivity, and correlated in an anomalous way with reward sensitivity in the HCRTR1 A/A homozygotes. Conclusively, the higher aggressiveness of HCRTR1 A/A homozygotes appears based on a qualitative difference in sensitivity to rewards, in the form that suggests their lower ability to prevent responses to challenges being converted into overt aggression.
Association of the COMT Val108/158Met genotype with professional career and education: The Val-allele is more frequent in managers and in enterprising occupations
(ScienceDirect, 2018-01) Kurrikoff, Triin; Kaarma, Katrin; Tooding, Liina-Mai; Vaht, Mariliis; Tulviste, Tiia; Veidebaum, Toomas; Harro, Jaanus
Catechol-O-methyl transferase (COMT) is a key player in neurotransmission by catecholamines, and the functional COMT Val108/158Met polymorphism is strongly related to prefrontal reactivity and to dopamine levels. As dopamine is a critically important neurotransmitter in cognition, emotion and motivation, we addressed the potential impact of this genotype on life course by examining its association with being in enterprising professions. The parents (n = 1410) of the target subjects in the Estonian Children Personality Behaviour and Health Study reported their current occupation, and those classified as enterprising (n = 197; 18%) were compared with the remaining group. Additionally, the subjects self-classified themselves according to the International Standard Classification of Occupations and the group of managers (6.2%) was compared to other groups. We found that the COMT Val108/158Met Val/Val homozygotes were overrepresented among enterprising occupations and the Val-allele carriers among self-classified managers. While several measures associated with the Val/Val homozygosity were also associated with enterprising occupation, no simple path from the genotype to enterprising occupations emerged from structural equation models, suggesting that the COMT Val108/158Met genotype contributes to choices of profession via multiple interactive features. We also reproduced a previous finding that the COMT genotype is associated with educational attainment in a gender-dependent manner.
Attention distractibility trait associations with self-reported attention deficit and with variation in KTN1 gene
(2018-08-28) Tuvi, Iiris; Harro, Jaanus; Kiive, Evelyn; Bachmann, Talis
Cholecystokinin 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, Jaanus
Objectives: 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.
Driving 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, Jaanus
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. 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.
Driving 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, Jaanus
Background: 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.
Efficacy 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, Jaanus
OBJECTIVE: 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.
Family 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
Is 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, Jaanus
Lower 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.
Kõrgkool ja psühholoogia
(Tartu Ülikool, 2013) Täht, Karin; Harro, Jaanus; Must, Olev; Realo, Anu
Kogumik „Kõrgkool ja psühholoogia“ on koostatud eesmärgiga tutvustada Tartu ülikooli psühholoogia instituudis aastail 2009–2013 korraldatud projekti „Kõrgkooli akadeemilist edukust mõjutavad tegurid“ (KAEMUS) peamisi tulemusi ning pakkuda seeläbi harivat ja põnevat lugemist kõigile, kes huvituvad ülikoolihariduse omandamise psühholoogilistest tahkudest.
Low cardiorespiratory fitness and obesity for ADHD in childhood and adolescence: A 6‐year cohort study
(2020-12-20) Muntaner Mas, Adrià; Ortega, Francisco B.; Femia, Pedro; Kiive, Evelyn; Evelyn, Diva; Mäestu, Jarek; Franke, Barbara; Reif, Andreas; Faraone, Stephen V.; Harro, Jaanus
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder in childhood and identifying risk factors associated with developing ADHD during childhood and adolescence is relevant from a clinical and epidemiological point of view. This work examines (1) whether overweight/obesity and low cardiorespiratory fitness (CRF) are associated with increased ADHD symptoms in childhood (cross sectional analysis), and (2) whether overweight/obesity and low CRF levels during childhood predict increased ADHD symptoms in adolescence (longitudinal analysis). Data were examined from a longitudinal study of Estonian inhabitants who took part in the European Youth Heart Study (EYHS) in 1998 and 1999 (baseline age 9 years), who were re-evaluated 6 years later as part of the longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS). CRF was determined via an incremental maximal cycle-ergometer test, overweight/obesity was based on body mass index (BMI), and the 7-point af Klinteberg Hyperactivity Scale was used to assess ADHD symptoms at both time points. In the cross-sectional analysis, children with overweight/obesity were at greater risk of ADHD symptoms compared to underweight/normal-weight children, as were those unfit compared to fit children (OR=1.92 and 95%CI=1.02–3.55, and OR=1.84 and 95%CI=1.13–2.98, respectively). The cross-sectional association between BMI and ADHD symptoms was mediated by CRF (z=2.116, 42.9%; p=0.034). The longitudinal analysis showed being unfit in childhood was associated with a greater risk of increased ADHD symptoms 6 years later in adolescence (OR=2.26 and 95%CI=1.14–4.47), even after adjusting for baseline ADHD symptoms and BMI. Our result suggests that being unfit is an additional risk factor for increased ADHD symptoms during childhood and adolescence. The association between BMI and ADHD symptoms was mediated by CRF in the cross-sectional analysis and no association was seen between overweight/obesity and increased ADHD symptoms.
Low cholesterol levels in children predict impulsivity in young adulthood
(2019) Tomson-Johanson, Katrin; Kaart, Tanel; Kiivet, Raul-Allan; Veidebaum, Toomas; Harro, Jaanus
Objective: 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.
Monoamiini oksüdaas A genotüüp ja metülatsioon modereerivad seost väärkohtlemise ning agressiivse ja impulsiivse käitumise vahel
(2022) Anja, Karolina; Harro, Jaanus; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Neuropeptide 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, Jaanus
Objective: 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.
Nice guys: Homozygocity for the TPH2 -703G/T (rs4570625) minor allele promotes low aggressiveness and low anxiety
(2017) Laas, Kariina; Kiive, Evelyn; Mäestu, Jarek; Vaht, Mariliis; Veidebaum, Toomas; Harro, Jaanus
Background: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. We examined whether the TPH2 polymorphism -703G/T (rs4570625) is associated with aggressiveness and impulsivity, and the prevalence of psychiatric disorders, in a population-representative sample. Methods: We used self and proxy reports on aggressive behaviour in the younger birth cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study collected at age 25, and earlier collected impulsivity and related data of both ECPBHS cohorts. Results: The TT homozygous males reported less aggressive behaviour in the Life History of Aggression interview at age 25. They also had significantly lower scores in Illinois Bully Scale peer reports, and less ADHD symptoms rated by teachers both at ages 9 and 15. The TT homozygotes of both sexes had the lowest Maladaptive Impulsivity at ages 18 and 25, and the highest Adaptive Impulsivity at age 25. The TT homozygotes also had low depressiveness and trait anxiety by age 25, and the odds ratio for the prevalence of anxiety disorders was 9.38 for the G-allele carriers. Limitations: The main limitation of the study is the naturally occurring low number of subjects with the TT genotype. Conclusions: Subjects with the TPH2 rs4570625 TT genotype, especially males, exhibit less aggression and a favourable impulsivity profile, and develop anxiety disorders by young adulthood less often.
Orexin/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, Toomas
Orexins, 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’.