From parents to children: associations of traffic risks with impulsivity, family relationships and serotonin transporter genotype.

Road traffic injuries are the leading cause of death for young adults, and parents play a major role in shaping their traffic behaviour. Higher impulsivity (predictor of higher traffic risk) has been shown to be dependent on family relations and the serotonin transporter gene promoter polymorphism (5-HTTLPR). The specific mechanisms for the inheritance of risky traffic behaviour from parents to children are not clear, and the genetic aspect has not been studied before. We used data of Estonian Children Personality Behaviour and Health Study subjects (n = 596, mean age = 25.2 ± 0.6) and their parents (mothers, n = 460, mean age = 52.1 ± 5.8; fathers, n = 339, mean age = 54.1 ± 6.5). Family relationships scale, traffic risk questionnaires and Adaptive and Maladaptive Impulsivity Scale were filled out. The increased risk-taking behaviour of parents and worse quality of family relationship were significant predictors of higher traffic risk among subjects. Family support and impulsivity of fathers significantly predicted the subjects' traffic risk score in interaction with 5-HTTLPR genotype: l'/l' homozygous subjects with adaptively impulsive fathers had higher traffic risk, whereas for s'-allele carrying subjects family support was more significant. Parental role modelling and family relationships are significant predictors of future traffic behaviour of the child. Whether the behavioural example of the father or the influence of family relationships is more important in predicting future risky traffic behaviour, depends on the 5-HTTLPR genotype of the child.

MAOA methylation is associated with impulsive and antisocial behaviour: dependence on allelic variation, family environment and diet.

Congenital absence of monoamine oxidase A (MAO-A) activity predisposes to antisocial impulsive behaviour, and the MAOA uVNTR low-expressing genotype (MAOA-L) together with childhood maltreatment is associated with similar phenotypes in males. A possible explanation of how family environment may lead to such behaviour involves DNA methylation. We have assessed MAOA methylation and impulsive/antisocial behaviour in 121 males from the Estonian Children Personality Behaviour and Health Study. Of the 12 CpG sites measured, methylation levels at the locus designated CpG3 were significantly lower in subjects with antisocial behaviour involving police contact. CpG3 methylation was lower in subjects with alcohol use disorder by age 25, but only in MAOA-H genotype. No correlation between MAOA CpG3 methylation levels and adaptive impulsivity was found at age 15, but in MAOA-L genotype a positive correlation appeared by age 18. By age 25, this positive correlation was no longer observed in subjects with better family relationships but had increased further with experience of adversity within the family. MAOA CpG3 methylation had different developmental dynamics in relation to maladaptive impulsivity. At age 18, a positive correlation was observed in MAOA-L genotype with inferior family relationships and a negative correlation was found in MAOA-H with superior home environment; both of these associations had disappeared by age 25. CpG3 methylation was associated with dietary intake of several micronutrients, most notable was a negative correlation with the intake of zinc, but also with calcium, potassium and vitamin E; a positive correlation was found with intake of phosphorus. In conclusion, MAOA CpG3 methylation is related to both maladaptive and adaptive impulsivity in adolescence in MAOA-L males from adverse home environment. By young adulthood, this relationship with maladaptive impulsivity had disappeared but with adaptive impulsivity strengthened. Thus, MAOA CpG3 methylation may serve as a marker for adaptive developmental neuroplasticity in MAOA-L genotype. The mechanisms involved may include dietary factors.

To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele.

INTRODUCTION: The role of catechol-O-methyltransferase (COMT) in catecholamine neurotransmitter metabolism has led to the investigation of variants of the corresponding gene in the etiology of different psychiatric disorders, but the results are inconclusive. METHODS: We have examined the relationship between COMT Val158Met single nucleotide polymorphism (rs4680) and the occurrence of psychiatric disorders in a highly representative birth cohort sample of young adults in the Estonian Children Personality Behaviour and Health Study (original n = 1,238). The lifetime occurrence of psychiatric disorders at the age of 25 years was assessed with the Mini-International Neuropsychiatric Interview. RESULTS: Both Val- and Met-alleles of the COMT Val158Met were associated with specific psychiatric disorders. Met-allele carriers had a significantly higher occurrence of agoraphobia (3.2% vs. 0.5%; χ2 = 4.10; p < 0.05) compared to Val/Val homozygotes. Also, the occurrence of panic disorder was significantly higher in female Met-allele carriers than in Val/Val homozygote females (10.2% vs. 3.6%; χ2 = 4.62 p = 0.03). In contrast, the occurrence of generalized anxiety disorder was higher in Val/Val females when compared to Met-allele carriers (12.7% vs. 6.8%; χ2 = 4.16; p = 0.04). Also, female Val/Val homozygotes (15.5%) had a higher occurrence of eating disorders than Met-allele carriers (6.1%) of the COMT Val158Met polymorphism (χ2 = 10.39; p = 0.002). In the whole sample, Met-allele homozygotes had a higher occurrence of alcohol use and substance use disorders than Val-allele carriers (χ2 = 3.62 and 3.68, respectively; p < 0.05). CONCLUSION: In a regional highly birth cohort representative sample, either COMT rs4680 variant was observed in association with specific psychiatric disorders.

Neuropeptide Y gene variants and Agreeableness: interaction effect with the birth cohort and the serotonin transporter promoter polymorphism.

OBJECTIVE: Neuropeptide Y (NPY) is a powerful regulator of anxious states, including social anxiety, but evidence from human genetic studies is limited. Associations of common gene variants with behaviour have been described as subject to birth cohort effects, especially if the behaviour is socially motivated. This study aimed to examine the association of NPY rs16147 and rs5574 with personality traits in highly representative samples of two birth cohorts of young adults, the samples having been formed during a period of rapid societal transition. METHODS: Both birth cohorts (original n = 1238) of the Estonian Children Personality Behaviour and Health Study (ECPBHS) self-reported personality traits of the five-factor model at 25 years of age. RESULTS: A significant interaction effect of the NPY rs16147 and rs5574 and birth cohort on Agreeableness was found. The T/T genotype of NPY rs16147 resulted in low Agreeableness in the older cohort (born 1983) and in high Agreeableness in the younger cohort (born 1989). The C/C genotype of NPY rs5574 was associated with higher Agreeableness in the younger but not in the older cohort. In the NPY rs16147 T/T homozygotes, the deviations from average in Agreeableness within the birth cohort were dependent on the serotonin transporter promoter polymorphism. CONCLUSIONS: The association between the NPY gene variants and a personality domain reflecting social desirability is subject to change qualitatively in times of rapid societal changes, serving as an example of the relationship between the plasticity genes and environment. The underlying mechanism may involve the development of the serotonergic system.

RNA m6A methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat.

Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

Genome-wide DNA methylation analysis of aggressive behaviour: a longitudinal population-based study.

BACKGROUND: Human aggression is influenced by an interplay between genetic predisposition and experience across the life span. This interaction is thought to occur through epigenetic mechanisms, inducing differential gene expression, thereby moderating neuronal cell and circuit function, and thus shaping aggressive behaviour. METHODS: Genome-wide DNA methylation (DNAm) levels were measured in peripheral blood obtained from 95 individuals participating in the Estonian Children Personality Behaviours and Health Study (ECPBHS) at 15 and 25 years of age. We examined the association between aggressive behaviour, as measured by Life History of Aggression (LHA) total score and DNAm levels both assessed at age 25. We further examined the pleiotropic effect of genetic variants regulating LHA-associated differentially methylated positions (DMPs) and multiple traits related to aggressive behaviours. Lastly, we tested whether the DNA methylomic loci identified in association with LHA at age 25 were also present at age 15. RESULTS: We found one differentially methylated position (DMP) (cg17815886; p = 1.12 × 10-8 ) and five differentially methylated regions (DMRs) associated with LHA after multiple testing adjustments. The DMP annotated to the PDLIM5 gene, and DMRs resided in the vicinity of four protein-encoding genes (TRIM10, GTF2H4, SLC45A4, B3GALT4) and a long intergenic non-coding RNA (LINC02068). We observed evidence for the colocalization of genetic variants associated with top DMPs and general cognitive function, educational attainment and cholesterol levels. Notably, a subset of the DMPs associated with LHA at age 25 also displayed altered DNAm patterns at age 15 with high accuracy in predicting aggression. CONCLUSIONS: Our findings highlight the potential role of DNAm in the development of aggressive behaviours. We observed pleiotropic genetic variants associated with identified DMPs, and various traits previously established to be relevant in shaping aggression in humans. The concordance of DNAm signatures in adolescents and young adults may have predictive value for inappropriate and maladaptive aggression later in life.

Association of Impulsivity With Food, Nutrients, and Fitness in a Longitudinal Birth Cohort Study.

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 (ß = -.07; 95% CI = -0.12; -0.03). Higher maladaptive impulsivity was associated with lower dietary intake of zinc (ß = -.10; -0.15; -0.06) and vegetables (ß = -.04; -0.07; -0.01) and higher intake of sodium (ß = .06; 0.02; 0.10). Vitamin B6 was positively associated with adaptive impulsivity (ß = .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.

Family Relationships and Alcohol Consumption: Interaction with the Serotonin Transporter Promoter Polymorphism (5-HTTLPR).

INTRODUCTION: The interaction of environmental and inherited factors determines how a young person becomes involved in problem behaviours such as drinking alcohol. We have investigated whether the association of family relationships with early experience with alcohol is related to variation in the serotonin transporter gene promoter region (5-HTTLPR). METHODS: We used data of the two birth cohorts of the Estonian Personality Behaviour and Health Study (original n = 1,238) at age 15 and 18 years. Data were self-reported in a laboratory setting. RESULTS: Family relationships at age 15 years were significantly related to the frequency of drinking alcohol. Specifically, association of Warmth in Family (closeness and support within family) with consuming alcohol was in a negative, while maltreatment (misprize and abuse) in a positive relationship with alcohol consumption. At age 18 years, the effects of family relationships on consuming alcohol were lower and no longer statistically significant (p values >0.10). The associations between family relations and alcohol use at age 15 years varied by the 5-HTTLPR genotype: at this age, the impact of the family relations, both Warmth and Maltreatment, on the frequency of drinking alcohol was statistically significant among participants with the S/L genotype, and while rather similar results were obtained for the S/S genotype, no relations were apparent between family relations and consuming alcohol in subjects with the L/L genotype. CONCLUSION: These findings reveal that family relations are related to alcohol consumption, dependent upon the 5-HTTLPR genotype. This is compatible with the hypothesis that the S-allele carriers are more malleable by the environment.

Driving risks of young drivers with symptoms of attention deficit hyperactivity disorder: association with the dopamine transporter gene VNTR polymorphism.

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 = 1,016, 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 9 R 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 9 R allele appears to aggravate these risks.

First-episode psychosis integrative treatment: Estonian experience.

PURPOSE: Research on first-episode psychosis early intervention has shown significant positive effects on psychopathological, functional and quality-of-life outcome measures. The effects reported have however been short-term and there is still only limited information about the long-term effects. This article will present the short-term results of an effectiveness study in a Baltic country and the first results of a registry-based long-term follow-up. METHODS: One hundred and ninety-nine first-episode psychosis patients were included in the early intervention effectiveness study in 2004-2008, and 107 were available for a follow-up after two years. Registry-based ten-year follow-up (n = 116) was conducted with a retrospectively formed control group (n = 114). RESULTS: Patients who received early intervention had substantial symptomatic improvement (BPRS score reduction > 50%) after 6 months of treatment, the Global Assessment of Functioning (GAF) scores were significantly improved after 6 months, and the quality of life after 12 months was significantly higher than at the beginning of treatment. After 2 years employment increased by 14% (43.9-57.9%). Long-term follow-up revealed that significantly fewer patients in the intervention group had been in supported housing compared to the control group. Patients in the intervention group had spent more time working during the follow-up period and had almost two times larger incomes, suggestive of higher employment/salary level. CONCLUSIONS: Early intervention with flexible duration has positive long-term effects on the functioning of patients.

Schoolchildren's autobiographical memory: COMT gene Val158Met polymorphism effects on emotional content and quality of first memories.

Autobiographical memory is a cognitive function strongly related to emotional processing as autobiographical memory often includes emotional content. The COMT gene Val158Met polymorphism is associated with both cognitive and emotional processing. COMT gene Val158Met polymorphism effects on the emotional content and quality of Estonian schoolchildren's first autobiographical memories were investigated in the present study. In addition, gender effects were considered and the emotional valence of the first memory was taken into account. Schoolchildren's (N = 234) first memories were coded for valence, emotion words, specificity, and details. Girls were more likely to provide specific memories and recollections with an emotional valence than boys were. Children described memories with a positive or a negative valence in more detail than neutral memories. Interactions between the COMT gene Val158Met polymorphism and gender and valence of the events were detected: Val/Met heterozygotes provided fewer details for emotional events; Val/Met heterozygote boys reported fewer details for their first memories than Val/Met heterozygote girls did; Met/Met homozygote children provided fewer evaluative details for emotional events.

Cholecystokinin B receptor gene polymorphism (rs2941026) is associated with anxious personality and suicidal thoughts in a longitudinal study.

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.

Low cardiorespiratory fitness and obesity for ADHD in childhood and adolescence: A 6-year cohort study.

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 (a) whether overweight/obesity and low cardiorespiratory fitness (CRF) are associated with increased ADHD symptoms in childhood (cross-sectional analysis), and (b) 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 = .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.

Variations in accelerometry measured physical activity and sedentary time across Europe - harmonized analyses of 47,497 children and adolescents.

BACKGROUND: Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. METHODS: Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2-18 years) from 18 different European countries. RESULTS: Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. CONCLUSIONS: Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.

Changes in cardiorespiratory fitness through adolescence predict metabolic syndrome in young adults.

BACKGROUND AND AIMS: Higher cardiorespiratory fitness (CRF) has been suggested to reduce the risk of metabolic syndrome (MetS). We aimed to longitudinally examine the changes of CRF on MetS and its risk factors from adolescence to adulthood. METHODS AND RESULTS: At the age of 15 years, 1076 subjects were recruited from 2 cohorts. CRF was measured on a cycle ergometer. MetS was classified as having at least 3 of the following parameters above the threshold of risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL), high blood pressure (BP) and fasting glucose. In addition, insulin, total cholesterol and low-density lipoprotein cholesterol were measured and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Persistently high, increasing, decreasing and persistently low CRF groups were formed according to change in CRF from adolescence to adulthood. Longitudinal increase in CRF was positively associated with change in HDL and negatively associated with change in insulin, HOMA-IR, triglycerides, BP and prevalence of MetS after adjustment for potential confounders. Subjects with persistently low CRF had 11.5- to 34.4-times higher risk of MetS at the age of 25 and 33 years compared to subjects with persistently high CRF and 14.6- to 15.9-times higher risk compared to the increasing CRF group. CONCLUSION: Higher CRF is strongly related to lower values of MetS risk factors. Increasing CRF from adolescence to adulthood reduces the risk to have MetS later in adulthood. High CRF in adolescence that decreases during adulthood has similar risks to MetS compared to individuals with persistently low CRF.

Association of FTO rs1421085 with obesity, diet, physical activity, and socioeconomic status: A longitudinal birth cohort study.

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.

Comparison of psychotropic medication use in the Baltic countries.

Purpose: While the pivotal role of pharmacotherapy in psychiatry is universal, significant regional differences exist in drug use patterns. Herewith we compare the use of ATC psychotropic drugs (N05, psycholeptics and N06A, antidepressants) in 2010-2015 in the three Baltic Countries with reference to the Nordic Countries.Methods: Data were obtained from the national authorities on medicines as expressed in DDD per 1000 inhabitants per day. A semi-structured questionnaire was used for expert statements on the rationale of current use of medicines.Results: During the observation period the use of antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants steadily increased, while the growth in use of anxiolytics stagnated in the more recent years. Antipsychotic use was the largest in Lithuania and the lowest in Estonia. The use on anxiolytics in Lithuania was more than twice of that in Estonia and Latvia. Conversely, the use of hypnotics and sedatives was about three times higher in Estonia than in Latvia or Lithuania. Antidepressant use was dominated by the selective serotonin reuptake inhibitors in all three countries, but overall was much lower in Latvia as compared to Lithuania and Estonia. As compared to the Nordic Countries in 2015, antidepressants are used at much lower level throughout Baltics, probably reflecting underdiagnostics of depression and anxiety disorders.Conclusion: While the health-care expenditures in Estonia, Latvia and Lithuania are largely similar, as is the cultural and recent political background of these EU member countries, the extent and the pattern of psychotropic drug use is remarkably variable.

Reward sensitivity, affective neuroscience personality, symptoms of attention-deficit/hyperactivity disorder, and TPH2-703G/T (rs4570625) genotype.

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. 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.

Low cholesterol levels in children predict impulsivity in young adulthood.

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 (original n = 1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale. RESULTS: Total and low-density lipoprotein (LDL) cholesterol measured in boys aged 9, 15 and 18 years predicted disinhibition and thoughtlessness in 25-year-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 the development of Maladaptive Impulsivity starting from an early age. This effect of cholesterol continues throughout adolescence into young adulthood.

Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study.

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 related to differences in metabolism than energy intake.