Jaanus Harro - Academia.edu (original) (raw)

Papers by Jaanus Harro

International Journal of Neuropsychopharmacology

Background Impulsivity is a psychiatric vulnerability factor strongly associated with substance a... more 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 us...

Acta Neuropsychiatrica

Objectives:Cholecystokinin is a neuropeptide with a role in the neurobiology of adaptive behaviou... more 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 rs29410...

Psychopharmacology, 2022

RATIONALE Platelet monoamine oxidase (MAO) activity, a marker of central serotonergic capacity, h... more 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 have not consistently linked MAO activity with addiction or reported 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 analysed by mixed-effects regression models. Differences at ages 15, 18 and 25 were analysed 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 analyses. 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.

Brain Sciences, 2021

Fifty-kHz ultrasonic vocalizations (USVs) in response to an imitation of rough-and-tumble play (‘... more Fifty-kHz ultrasonic vocalizations (USVs) in response to an imitation of rough-and-tumble play (‘tickling’) have been associated with positive affective states and rewarding experience in the rat. This USV response can be used as a measure of inter-individual differences in positive affect. We have previously shown that rats with persistently low positive affectivity are more vulnerable to the effects of chronic variable stress (CVS). To examine whether these differential responses are associated with dopaminergic neurotransmission in the nucleus accumbens (NAc), juvenile male Wistar rats were categorized as of high or low positive affectivity (HC and LC, respectively), and after reaching adulthood, extracellular dopamine (DA) levels in the NAc shell were measured using in vivo microdialysis after three weeks of CVS. Baseline levels of DA were compared as well as the response to K+-induced depolarization and the effect of glial glutamate transporter EAAT2 inhibition by 4 mM l-trans-...

Peptides, 2021

Objective: Neuropeptide Y affects several physiological functions, notably appetite regulation. W... more 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 TThomozygotes 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.

Pharmaceuticals, 2021

Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness an... more Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness and arousal with simultaneous anxiety reduction, in some inconsistency with results in humans. We examined the effect of NPS on rat ultrasonic vocalizations (USV) as an index of affective state and on behaviour in novel environments in rats with persistent inter-individual differences in exploratory activity. Adult male Wistar rats were categorised as of high (HE) or low (LE) exploratory activity and NPS was administered intracerebroventricularly (i.c.v.) at a dose of 1.0 nmol/5 µL, after which USVs were recorded in the home-cage and a novel standard housing cage, and behaviour evaluated in exploration/anxiety tests. NPS induced a massive production of long and short 22 kHz USVs in the home cage that continued later in the novel environment; no effect on 50 kHz USVs were found. In LE-rats, the long 22 kHz calls were emitted at lower frequencies and were louder. The effects of NPS on behavi...

Acta Neuropsychiatrica, 2020

Objective:Reward sensitivity is an increasingly used construct in psychiatry, yet its possible in... more Objective: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....

Acta Neuropsychiatrica, 2019

Objective:Severe behavioural issues such as impulsive action and suicide have since long been ass... more 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, no longitudinal studies showed the 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 (originaln= 1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale.Results:Total and low-dens...

International Journal of Obesity, 2019

BACKGROUND: The development of obesity has a large genetic component, and the gene encoding the t... more BACKGROUND: The development of obesity has a large genetic component, and the gene encoding the transcription factor 2 beta (TFAP2B) has been identified as one of the responsible factors. We investigated the effect of TFAP2B intron 2 variable number tandem repeat (VNTR) genotype on obesity, insulin resistance and dietary intake from 15 to 33 years of age. METHODS: The sample included both birth cohorts (originally n = 1176) of the longitudinal Estonian Children Personality Behaviour and Health Study. The association between TFAP2B genotype, and anthropometric measurements, glucose metabolism and dietary intake at ages 15, 18 and 25 years was assessed using the linear mixed-effects regression models. Differences in anthropometric measurements, biochemical measures, blood pressure and dietary intake between TFAP2B genotypes at different age, including data of the older cohort at age 33, were assessed by one-way ANOVA. RESULTS: Male homozygotes for the TFAP2B 5-repeat allele had significantly higher body weight, body mass index, sum of 5 skinfolds, proportion of body fat, waist circumference, hip circumference, waist to hip ratio, waist to height ratio, fasting insulin and HOMA index. In female subjects, homozygotes for the TFAP2B 5-repeat allele had significantly larger increase in the rate of change per year in body weight, body mass index and hip circumference between years 15 and 25. By age 33 the findings were similar. A decrease in daily energy intake from adolescence to young adulthood was observed. In males, heterozygotes had significantly smaller decrease in the rate of change per year in daily energy intake. CONCLUSIONS: The association of TFAP2B with the development of obesity and insulin resistance is present throughout adolescence to young adulthood in males. In females the effect of TFAP2B on obesity appears later, in young adulthood. The TFAP2B effect is rather 52 related to differences in metabolism than energy intake.

Acta Neuropsychiatrica, 2019

ObjectiveRoad traffic injuries are the leading cause of death among young people. Recognition of ... more ObjectiveRoad 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.MethodsDriving 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...

Neuropharmacology, 2019

Highlights • Orexins are involved in the regulation of stress response • The HCRTR1 rs2271933 G>A... more Highlights • Orexins are involved in the regulation of stress response • The HCRTR1 rs2271933 G>A genotype was associated with aggressiveness • A/A homozygotes were more aggressive and relapsed to drunk driving • A-allele carriers were more frequently involved in traffic accidents • The genotype effect is sensitive to stressful life events

Acta Neuropsychiatrica, 2018

ObjectiveIndividual biological predispositions should play a role in risky driving behaviour. Pla... more ObjectiveIndividual 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.MethodsWe 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.ResultsTh...

Acta psychologica, 2017

It is unclear if positive, negative, or neutral emotional expressions have an advantage in short-... more It is unclear if positive, negative, or neutral emotional expressions have an advantage in short-term recognition. Moreover, it is unclear from previous studies of working memory for emotional faces whether effects of emotions comprise response bias or sensitivity. The aim of this study was to compare how schematic emotional expressions (sad, angry, scheming, happy, and neutral) are discriminated and recognized in an updating task (2-back recognition) in a representative sample of birth cohort of young adults. Schematic facial expressions allow control of identity processing, which is separate from expression processing, and have been used extensively in attention research but not much, until now, in working memory research. We found that expressions with a U-curved mouth (i.e., upwardly curved), namely happy and scheming expressions, favoured a bias towards recognition (i.e., towards indicating that the probe and the stimulus in working memory are the same). Other effects of emotio...

International Journal of Neuropsychopharmacology, 2016

Background: Inter-individual differences in the monoaminergic systems have been shown to moderate... more Background: Inter-individual differences in the monoaminergic systems have been shown to moderate the risk for a lifetime history of anxiety, affective, and alcohol use disorders. A common single nucleotide polymorphism in the vesicular monoamine transporter 1 gene (VMAT1 rs1390938 G/A; Thr136Ile) has been reported as functional in vitro and associated with bipolar disorder and anxiety. We aimed at assessing the association between the VMAT1 genotype, affect, and affectrelated psychiatric disorders in a longitudinal population-representative study. Methods: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9-(recalled at ages 15 and 18 years, n = 579) and 15-(recalled at ages 18 and 25 years; n = 654) year-old children provided self-reports on impulsivity, anxiety, depressiveness, neuroticism, and alcohol use. In addition, psychiatric assessment based on DSM-IV was carried out in the older cohort at age 25 years. Results: Subjects homozygous for the less prevalent A (136Ile) allele reported lower maladaptive impulsivity, state and trait anxiety, depressiveness, and neuroticism and were less likely to have been diagnosed with an affective, anxiety, and/or alcohol use disorder by young adulthood. While in the younger cohort alcohol use started at younger age, this birth cohort effect was dependent on genotype: only G allele carriers and in particular the GG homozygotes started alcohol use earlier. Conclusions: VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in the general population. Subjects homozygous for the "hyperfunction" allele (AA; Ile/Ile) appear to be more resilient to these disorders.

European Neuropsychopharmacology, 2016

Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and ... more Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and altered dendritic development. Amongst the most promising candidate molecules for schizophrenia are neuronal nitric oxide (NO) synthase (NOS-I, also known as nNOS) and its adapter protein NOS1AP (previously named CAPON). However, the precise molecular mechanisms by which NOS-I and NOS1AP affect disease pathology remain to be resolved. Interestingly, overexpression of NOS1AP affects dendritic morphology, possibly through increased association with the NOS-I PDZ domain. To investigate the effect of NOS1AP on dendritic morphology we overexpressed different NOS1AP isoforms, NOS1AP deletion mutants and the aminoterminal 133 amino acids of NOS-I (NOS-IN133) containing an extended PDZ domain. We examined the interaction of the overexpressed constructs with endogenous NOS-I by co-immunoprecipitation and the consequences of increased NOS-I/NOS1AP PDZ interaction in primary cultures of hippocampal and cortical neurons from C57BL/6J mice. Neurons overexpressing NOS1AP isoforms or deletion mutants showed highly altered spine morphology and excessive growth of filopodia-like protrusions. Sholl analysis of immunostained primary cultured neurons revealed that dendritic branching was mildly affected by NOS1AP overexpression. Our results hint towards an involvement of NOS-I/NOS1AP interaction in the regulation of dendritic spine plasticity. As altered dendritic spine development and filopodial outgrowth are important neuropathological features of schizophrenia, our findings may provide insight into part of the molecular mechanisms involved in brain morphology alterations observed in schizophrenia. As the NOS-I/NOS1AP interface can be targeted by small molecules, our findings ultimately might help to develop novel treatment strategies for schizophrenia patients.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2016

Emotional facial stimuli are important social signals that are essential to be perceived and reco... more Emotional facial stimuli are important social signals that are essential to be perceived and recognized in order to make appropriate decisions and responses in everyday communication. The ability to voluntarily guide attention to perceive and recognize emotions, and react to them varies largely across individuals, and has a strong genetic component (Friedman et al., 2008). Two key genetic variants of the catecholamine system that have been related to emotion perception and attention are the catechol-O-methyl transferase genetic variant (COMT Val158Met) and the α2A-receptor gene promoter polymorphism (ADRA2A C-1291G) accordingly. So far, the interaction of the two with sex in emotion perception has not been studied. Multilevel modeling method was applied to study how COMT Val158Met, ADRA2A C-1291G and sex are associated with measures of emotion perception in a large sample of young adults. Participants (n=506) completed emotion recognition and behavioral emotion detection tasks. It was found that COMT Val158Met genotype in combination with the ADRA2A C-1291G and sex predicts emotion detection, and perception of valence and arousal. In simple visual detection, the ADRA2A C-1291G G-allele leads to slower detection of a highly arousing face (scheming), which is modulated by each additional COMT Val158Met Met-allele and male sex predicting faster responses. The combination of G-allele, Met-allele and male sex also predicts higher perceived negativity in sad faces. No effects of C-1291G, Val158Met, and sex were found on verbal emotion recognition. Applying the findings to study the interplay between catecholamine-O-methyl transferase activity and α2A-receptors in emotion perception disorders (such as ADHD, autism and schizophrenia) in men and women would be the next step towards understanding individual differences in emotion perception.

Journal of Psychopharmacology, 2010

Suicide is a complex and challenging human phenomenon, and, although knowledge is expanding conce... more Suicide is a complex and challenging human phenomenon, and, although knowledge is expanding concerning its risk factors, its background is still not fully understood. There is currently an increasing interest in genetic factors associated with suicide, since these may lead to the emergence of personality traits and temperaments that may be long-term predictors of suicidal behaviour. One of the most likely genetic candidates in the background of suicide is the 5-HTTLPR polymorphism of the serotonin transporter gene. This review focused on papers published on the association of the 5-HTTLPR polymorphism of the serotonin transporter gene and suicidal behaviour as well as research on possible endophenotypes related to suicide. Although there are contradictory results, several studies and meta-analyses support the idea that the S allele plays a role in the background of violent suicide. However, in order to be able to delineate the genetic background of suicide, different types of suicid...

European Psychiatry, 2013

The COMT Val158Met polymorphism has been associated with anxiety and affective disorders, but its... more The COMT Val158Met polymorphism has been associated with anxiety and affective disorders, but its effect on anxiety-related personality traits varies between studies. Our purpose was to investigate the effect of COMT Val158Met on personality traits from adolescence to young adulthood in a population representative Caucasian birth cohort. Also its association with educational attainment and anxiety and mood disorders by the age 25 were examined. This analysis is based on the older cohort of the Estonian Children Personality Behavior and Health Study (original number of subjects 593). The personality traits were assessed when the participants were 15, 18 and 25 years old. COMT Val158Met had an effect on Neuroticism in females by age 25 (p = 0.001, Bonferroni-corrected for five traits), whereas female Val homozygotes scored the highest. In addition, the Conscientiousness scores of subjects with Val/Val genotype were decreasing in time, being the lowest by the age 25 (p = 0.006, Bonferr...

International Journal of Neuropsychopharmacology

Background Impulsivity is a psychiatric vulnerability factor strongly associated with substance a... more 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 us...

Acta Neuropsychiatrica

Objectives:Cholecystokinin is a neuropeptide with a role in the neurobiology of adaptive behaviou... more 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 rs29410...

Psychopharmacology, 2022

RATIONALE Platelet monoamine oxidase (MAO) activity, a marker of central serotonergic capacity, h... more 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 have not consistently linked MAO activity with addiction or reported 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 analysed by mixed-effects regression models. Differences at ages 15, 18 and 25 were analysed 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 analyses. 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.

Brain Sciences, 2021

Fifty-kHz ultrasonic vocalizations (USVs) in response to an imitation of rough-and-tumble play (‘... more Fifty-kHz ultrasonic vocalizations (USVs) in response to an imitation of rough-and-tumble play (‘tickling’) have been associated with positive affective states and rewarding experience in the rat. This USV response can be used as a measure of inter-individual differences in positive affect. We have previously shown that rats with persistently low positive affectivity are more vulnerable to the effects of chronic variable stress (CVS). To examine whether these differential responses are associated with dopaminergic neurotransmission in the nucleus accumbens (NAc), juvenile male Wistar rats were categorized as of high or low positive affectivity (HC and LC, respectively), and after reaching adulthood, extracellular dopamine (DA) levels in the NAc shell were measured using in vivo microdialysis after three weeks of CVS. Baseline levels of DA were compared as well as the response to K+-induced depolarization and the effect of glial glutamate transporter EAAT2 inhibition by 4 mM l-trans-...

Peptides, 2021

Objective: Neuropeptide Y affects several physiological functions, notably appetite regulation. W... more 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 TThomozygotes 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.

Pharmaceuticals, 2021

Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness an... more Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness and arousal with simultaneous anxiety reduction, in some inconsistency with results in humans. We examined the effect of NPS on rat ultrasonic vocalizations (USV) as an index of affective state and on behaviour in novel environments in rats with persistent inter-individual differences in exploratory activity. Adult male Wistar rats were categorised as of high (HE) or low (LE) exploratory activity and NPS was administered intracerebroventricularly (i.c.v.) at a dose of 1.0 nmol/5 µL, after which USVs were recorded in the home-cage and a novel standard housing cage, and behaviour evaluated in exploration/anxiety tests. NPS induced a massive production of long and short 22 kHz USVs in the home cage that continued later in the novel environment; no effect on 50 kHz USVs were found. In LE-rats, the long 22 kHz calls were emitted at lower frequencies and were louder. The effects of NPS on behavi...

Acta Neuropsychiatrica, 2020

Objective:Reward sensitivity is an increasingly used construct in psychiatry, yet its possible in... more Objective: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....

Acta Neuropsychiatrica, 2019

Objective:Severe behavioural issues such as impulsive action and suicide have since long been ass... more 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, no longitudinal studies showed the 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 (originaln= 1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale.Results:Total and low-dens...

International Journal of Obesity, 2019

BACKGROUND: The development of obesity has a large genetic component, and the gene encoding the t... more BACKGROUND: The development of obesity has a large genetic component, and the gene encoding the transcription factor 2 beta (TFAP2B) has been identified as one of the responsible factors. We investigated the effect of TFAP2B intron 2 variable number tandem repeat (VNTR) genotype on obesity, insulin resistance and dietary intake from 15 to 33 years of age. METHODS: The sample included both birth cohorts (originally n = 1176) of the longitudinal Estonian Children Personality Behaviour and Health Study. The association between TFAP2B genotype, and anthropometric measurements, glucose metabolism and dietary intake at ages 15, 18 and 25 years was assessed using the linear mixed-effects regression models. Differences in anthropometric measurements, biochemical measures, blood pressure and dietary intake between TFAP2B genotypes at different age, including data of the older cohort at age 33, were assessed by one-way ANOVA. RESULTS: Male homozygotes for the TFAP2B 5-repeat allele had significantly higher body weight, body mass index, sum of 5 skinfolds, proportion of body fat, waist circumference, hip circumference, waist to hip ratio, waist to height ratio, fasting insulin and HOMA index. In female subjects, homozygotes for the TFAP2B 5-repeat allele had significantly larger increase in the rate of change per year in body weight, body mass index and hip circumference between years 15 and 25. By age 33 the findings were similar. A decrease in daily energy intake from adolescence to young adulthood was observed. In males, heterozygotes had significantly smaller decrease in the rate of change per year in daily energy intake. CONCLUSIONS: The association of TFAP2B with the development of obesity and insulin resistance is present throughout adolescence to young adulthood in males. In females the effect of TFAP2B on obesity appears later, in young adulthood. The TFAP2B effect is rather 52 related to differences in metabolism than energy intake.

Acta Neuropsychiatrica, 2019

ObjectiveRoad traffic injuries are the leading cause of death among young people. Recognition of ... more ObjectiveRoad 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.MethodsDriving 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...

Neuropharmacology, 2019

Highlights • Orexins are involved in the regulation of stress response • The HCRTR1 rs2271933 G>A... more Highlights • Orexins are involved in the regulation of stress response • The HCRTR1 rs2271933 G>A genotype was associated with aggressiveness • A/A homozygotes were more aggressive and relapsed to drunk driving • A-allele carriers were more frequently involved in traffic accidents • The genotype effect is sensitive to stressful life events

Acta Neuropsychiatrica, 2018

ObjectiveIndividual biological predispositions should play a role in risky driving behaviour. Pla... more ObjectiveIndividual 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.MethodsWe 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.ResultsTh...

Acta psychologica, 2017

It is unclear if positive, negative, or neutral emotional expressions have an advantage in short-... more It is unclear if positive, negative, or neutral emotional expressions have an advantage in short-term recognition. Moreover, it is unclear from previous studies of working memory for emotional faces whether effects of emotions comprise response bias or sensitivity. The aim of this study was to compare how schematic emotional expressions (sad, angry, scheming, happy, and neutral) are discriminated and recognized in an updating task (2-back recognition) in a representative sample of birth cohort of young adults. Schematic facial expressions allow control of identity processing, which is separate from expression processing, and have been used extensively in attention research but not much, until now, in working memory research. We found that expressions with a U-curved mouth (i.e., upwardly curved), namely happy and scheming expressions, favoured a bias towards recognition (i.e., towards indicating that the probe and the stimulus in working memory are the same). Other effects of emotio...

International Journal of Neuropsychopharmacology, 2016

Background: Inter-individual differences in the monoaminergic systems have been shown to moderate... more Background: Inter-individual differences in the monoaminergic systems have been shown to moderate the risk for a lifetime history of anxiety, affective, and alcohol use disorders. A common single nucleotide polymorphism in the vesicular monoamine transporter 1 gene (VMAT1 rs1390938 G/A; Thr136Ile) has been reported as functional in vitro and associated with bipolar disorder and anxiety. We aimed at assessing the association between the VMAT1 genotype, affect, and affectrelated psychiatric disorders in a longitudinal population-representative study. Methods: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9-(recalled at ages 15 and 18 years, n = 579) and 15-(recalled at ages 18 and 25 years; n = 654) year-old children provided self-reports on impulsivity, anxiety, depressiveness, neuroticism, and alcohol use. In addition, psychiatric assessment based on DSM-IV was carried out in the older cohort at age 25 years. Results: Subjects homozygous for the less prevalent A (136Ile) allele reported lower maladaptive impulsivity, state and trait anxiety, depressiveness, and neuroticism and were less likely to have been diagnosed with an affective, anxiety, and/or alcohol use disorder by young adulthood. While in the younger cohort alcohol use started at younger age, this birth cohort effect was dependent on genotype: only G allele carriers and in particular the GG homozygotes started alcohol use earlier. Conclusions: VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in the general population. Subjects homozygous for the "hyperfunction" allele (AA; Ile/Ile) appear to be more resilient to these disorders.

European Neuropsychopharmacology, 2016

Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and ... more Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and altered dendritic development. Amongst the most promising candidate molecules for schizophrenia are neuronal nitric oxide (NO) synthase (NOS-I, also known as nNOS) and its adapter protein NOS1AP (previously named CAPON). However, the precise molecular mechanisms by which NOS-I and NOS1AP affect disease pathology remain to be resolved. Interestingly, overexpression of NOS1AP affects dendritic morphology, possibly through increased association with the NOS-I PDZ domain. To investigate the effect of NOS1AP on dendritic morphology we overexpressed different NOS1AP isoforms, NOS1AP deletion mutants and the aminoterminal 133 amino acids of NOS-I (NOS-IN133) containing an extended PDZ domain. We examined the interaction of the overexpressed constructs with endogenous NOS-I by co-immunoprecipitation and the consequences of increased NOS-I/NOS1AP PDZ interaction in primary cultures of hippocampal and cortical neurons from C57BL/6J mice. Neurons overexpressing NOS1AP isoforms or deletion mutants showed highly altered spine morphology and excessive growth of filopodia-like protrusions. Sholl analysis of immunostained primary cultured neurons revealed that dendritic branching was mildly affected by NOS1AP overexpression. Our results hint towards an involvement of NOS-I/NOS1AP interaction in the regulation of dendritic spine plasticity. As altered dendritic spine development and filopodial outgrowth are important neuropathological features of schizophrenia, our findings may provide insight into part of the molecular mechanisms involved in brain morphology alterations observed in schizophrenia. As the NOS-I/NOS1AP interface can be targeted by small molecules, our findings ultimately might help to develop novel treatment strategies for schizophrenia patients.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2016

Emotional facial stimuli are important social signals that are essential to be perceived and reco... more Emotional facial stimuli are important social signals that are essential to be perceived and recognized in order to make appropriate decisions and responses in everyday communication. The ability to voluntarily guide attention to perceive and recognize emotions, and react to them varies largely across individuals, and has a strong genetic component (Friedman et al., 2008). Two key genetic variants of the catecholamine system that have been related to emotion perception and attention are the catechol-O-methyl transferase genetic variant (COMT Val158Met) and the α2A-receptor gene promoter polymorphism (ADRA2A C-1291G) accordingly. So far, the interaction of the two with sex in emotion perception has not been studied. Multilevel modeling method was applied to study how COMT Val158Met, ADRA2A C-1291G and sex are associated with measures of emotion perception in a large sample of young adults. Participants (n=506) completed emotion recognition and behavioral emotion detection tasks. It was found that COMT Val158Met genotype in combination with the ADRA2A C-1291G and sex predicts emotion detection, and perception of valence and arousal. In simple visual detection, the ADRA2A C-1291G G-allele leads to slower detection of a highly arousing face (scheming), which is modulated by each additional COMT Val158Met Met-allele and male sex predicting faster responses. The combination of G-allele, Met-allele and male sex also predicts higher perceived negativity in sad faces. No effects of C-1291G, Val158Met, and sex were found on verbal emotion recognition. Applying the findings to study the interplay between catecholamine-O-methyl transferase activity and α2A-receptors in emotion perception disorders (such as ADHD, autism and schizophrenia) in men and women would be the next step towards understanding individual differences in emotion perception.

Journal of Psychopharmacology, 2010

Suicide is a complex and challenging human phenomenon, and, although knowledge is expanding conce... more Suicide is a complex and challenging human phenomenon, and, although knowledge is expanding concerning its risk factors, its background is still not fully understood. There is currently an increasing interest in genetic factors associated with suicide, since these may lead to the emergence of personality traits and temperaments that may be long-term predictors of suicidal behaviour. One of the most likely genetic candidates in the background of suicide is the 5-HTTLPR polymorphism of the serotonin transporter gene. This review focused on papers published on the association of the 5-HTTLPR polymorphism of the serotonin transporter gene and suicidal behaviour as well as research on possible endophenotypes related to suicide. Although there are contradictory results, several studies and meta-analyses support the idea that the S allele plays a role in the background of violent suicide. However, in order to be able to delineate the genetic background of suicide, different types of suicid...

European Psychiatry, 2013

The COMT Val158Met polymorphism has been associated with anxiety and affective disorders, but its... more The COMT Val158Met polymorphism has been associated with anxiety and affective disorders, but its effect on anxiety-related personality traits varies between studies. Our purpose was to investigate the effect of COMT Val158Met on personality traits from adolescence to young adulthood in a population representative Caucasian birth cohort. Also its association with educational attainment and anxiety and mood disorders by the age 25 were examined. This analysis is based on the older cohort of the Estonian Children Personality Behavior and Health Study (original number of subjects 593). The personality traits were assessed when the participants were 15, 18 and 25 years old. COMT Val158Met had an effect on Neuroticism in females by age 25 (p = 0.001, Bonferroni-corrected for five traits), whereas female Val homozygotes scored the highest. In addition, the Conscientiousness scores of subjects with Val/Val genotype were decreasing in time, being the lowest by the age 25 (p = 0.006, Bonferr...