Evelyn Kiive

Platelet monoamine oxidase in healthy 9- and 15-years old children: the effect of gender, smoking and puberty.

1. The effect of gender, smoking and pubertal development on platelet monoamine oxidase (MAO) activity was described in a randomly selected, large sample of 9- and 15-years old healthy children. 2. Platelet MAO activity was measured in 1129 children by a radioenzymatic method with beta-phenylethylamine as the substrate. Smoking habits were reported in an anonymous questionnaire. Pubertal status was assessed visually using Tanners stages. 3. Boys, younger children and smokers had significantly lower platelet MAO activity than girls, older children and non-smokers, respectively. Girls in Tanners stage V for breast and pubic hair development had significantly lower MAO than girls in stage IV. 4. Differences in gender, age, pubertal status and smoking habits must be taken into account if the relationship between platelet MAO activity, personality and psychiatric disorders is studied in children.

Association between substance use, personality traits and platelet MAO activity in preadolescents and adolescents

This study examined the relationship between alcohol/illicit drug use, the Five-Factor Model (FFM) personality traits, aggressiveness (Agg), and hyperactivity (Hyp), and platelet monoamine oxidase (MAO) activity in a population-derived representative sample of preadolescents and adolescents (n=1172). Alcohol and illicit drug use was self-reported. The FFM personality inventories were filled in by mothers of the participants, and Agg and Hyp were rated by their class teachers. Higher scores in extraversion (E), Agg, and Hyp and lower scores in conscientiousness (C) together with older age were significant predictors of more frequent alcohol use in adolescents. No significant association was found between alcohol illicit drug use, and platelet MAO activity.

The impact of adverse life events and the serotonin transporter gene promoter polymorphism on the development of eating disorder symptoms

Adverse life events have been shown to predict weight fluctuations and dietary restraint, as well as eating disorders during adolescence or early adulthood. Since the s-allele carriers of the 5-HTT gene-linked polymorphic region (5-HTTLPR) are biologically more reactive to stress related stimuli, we aimed to explore whether the eating disturbances are predicted by environmental stressors and moderated by the 5-HTTLPR genotype. The sample was based on the younger cohort of the Estonian Children Personality, Behaviour and Health Study and included those participating in its second and third wave. The history of stressful life events was self-reported at age 15. Data on eating behaviour and attitudes, anxiety, impulsivity and depressiveness were collected at age 18. The effect of the adverse life events on binge eating and on drive for thinness was found to be moderated by the 5-HTTLPR. Adolescent girls who at age 15 had reported a history of frequent adverse life events had elevated scores in EDI-2 Bulimia subscale at age 18 if they were carrying the s-allele. The effect of the s-allele on binge eating was even more pronounced when solely the experience of sexual abuse was considered. The interaction effect of the 5-HTTLPR and the past sexual abuse was also observed on drive for thinness. These data give further support to the idea that adverse life events in childhood may heighten susceptibility to serotonergic dysregulation following stress, and suggest that in individuals vulnerable to eating disorders this may result in disturbed eating behaviours.

Growth hormone, cortisol and prolactin responses to physical exercise: higher prolactin response in depressed patients

This study was designed to compare growth hormone, cortisol and prolactin responses to physical exercise in depressed patients and healthy comparison subjects. Patients fulfilled the DSM-IV diagnostic criteria for current major depressive disorder; subjective depressive symptoms were rated with Montgomery-Asberg Depression Rating Scale (MADRS) immediately before the experiment. Growth hormone, cortisol and prolactin were measured before and immediately after physiologically stressful bicycle cardiopulmonary exercise test. After exercise, there were three additional hormone measurements, with 30-min intervals. No significant difference was found in baseline growth hormone, cortisol or prolactin levels between patients and the control group. Plasma growth hormone and cortisol levels increased significantly during physical exercise in both patients and controls and returned to baseline in 90 min. There was no significant difference in growth hormone or cortisol responses to physical exercise between the two groups. However, prolactin levels increased only in the depressed patients group during the exercise. We hypothesize that acute exercise may have a stronger effect on serotonin (5-HT) release in depressed patients, which is reflected in increased plasma prolactin concentration.

Effect of α2A-adrenoceptor C-1291G genotype and maltreatment on hyperactivity and inattention in adolescents

The C-1291G polymorphism (rs1800544) in the promoter region of the alpha(2A)-adrenoceptor gene (ADRA2A) has been associated with attention deficit and hyperactivity in clinical samples. We have examined the effect of ADRA2A C-1291G on inattentive, hyperactive and aggressive behaviour in a population representative cohort of healthy schoolchildren, and possible interaction of genotype with family relations. Ratings on aggressiveness, motor restlessness and concentration difficulties were obtained from the class teachers by using the Hyperactivity Scale of af Klinteberg, and the teacher-report version of SNAP-IV. The relations in the family were reported by children. Symptom scores, self-reports and genotype data of 429 15-years old children (196 boys, 233 girls) were available for analysis. There was a significant interaction effect of maltreatment and the ADRA2A genotype on behavioural functioning in 15years old boys. Boys with CC genotype and higher score of maltreatment demonstrated more overactive behaviour and concentration difficulties than boys with CC genotype and low maltreatment score. They also had more inattentive symptoms measured by SNAP-IV. Among boys with low maltreatment score, subjects with CC genotype demonstrated less overactivity than G allele carriers. In girls, the G allele carriers did not differ from the CC genotype, but in maltreated girls with GG genotype aggression and inattention symptoms were reduced, and the score of aggressive behaviour was also lower compared to maltreated girls with CC genotype. Our data suggest that family environmental factors may act together with the alpha(2A)-adrenoceptor genotype to increase the expression of hyperactive and inattentive symptoms in adolescents.

A functional NPSR1 gene variant and environment shape personality and impulsive action: A longitudinal study

Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety. We examined whether the NPSR1 gene functional polymorphism Asn107Ile (rs324981, A>T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE). We used self-reports or teachers’ ratings for both the younger (n=593) and older (n=583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Males with the TT genotype displayed more ADHD-related symptoms. Adaptive impulsivity and Extraversion increased the most from age 18 to 25. While highest increases were observed in AA men, TT women exhibited the largest decreases. For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity. High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects. We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity- and anxiety-mediating role of NPSR1. Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.

Autoantibodies reacting with vasopressin and oxytocin in relation to cortisol secretion in mild and moderate depression

BACKGROUND Abnormal vasopressin (VP) and oxytocin (OT) signaling may contribute to the altered activity of the hypothalamo-pituitary-adrenal (HPA) axis in major depression; however, the underlying mechanisms remain uncertain. This study characterized plasma levels and affinities of OT- and VP-reactive autoantibodies (autoAbs) in relation to disease severity and plasma cortisol response to physical exercise in patients with mild and moderate depression and healthy controls. METHODS Physical exercise was used to elicit plasma cortisol response in 23 male patients with depression and 20 healthy controls and plasma samples were obtained before and after the exercise. Just before the exercise, patients and controls were evaluated by the Montgomery and Åsberg Depression Rating Scale (MADRS) and divided according to depression severity (14 mild and 9 moderate). Plasma levels of total and free VP- and OT-reactive IgG, IgA and IgM autoAbs were measured by ELISA and affinity of IgG and IgM autoAbs were measured by plasmon resonance technique at baseline before the exercise and analyzed with relation to the MADRS and cortisol response. Immunohistochemistry was used to evaluate autoAbs binding to the rat hypothalamus. RESULTS Plasma levels of OT- and VP-reactive total IgG autoAbs were lower in patients with moderate depression vs. controls and patients with mild depression. Plasma levels of both OT- and VP-free IgG autoAbs were negatively correlated with MADRS scores. Affinity values of IgG and IgM autoAbs for both OT and VP displayed 100 fold variability among patients or controls but no significant group differences were found. Patients with moderate depression displayed blunted response of cortisol secretion to physical exercise. Baseline levels of VP total IgG and IgM autoAbs correlated negatively and VP-free IgG autoAbs correlated positively with plasma cortisol after physical exercise. Immunostaining of magnocellular hypothalamic neurons of the supraoptic and paraventricular nuclei by plasma IgG was present in 35% of the depression and in 14% of the controls groups, but this staining was not abolished by plasma preabsorption with OT or VP peptides. CONCLUSION These data show that changes of levels but not affinity of OT- and VP-reactive autoAbs can be associated with the altered mood in subjects with moderate depression and that levels of VP-reactive autoAbs are associated with cortisol secretion.

Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness

A functional promoter polymorphism of the nitric oxide synthase 1 gene first exon 1f variable number tandem repeat (NOS1 ex1f-VNTR) is associated with impulsivity and related psychopathology. Facets of impulsivity are strongly associated with personality traits; maladaptive impulsivity with neuroticism; and adaptive impulsivity with extraversion. Both high neuroticism and low extraversion predict anxiety and depressive symptoms. The aim of the present study was to evaluate the effect of the NOS1 ex1f-VNTR genotype and possible interaction with environmental factors on personality, anxiety, and depressiveness in a population-representative sample. Short allele carriers had higher neuroticism and anxiety than individuals with the long/long (l/l) genotype. Male short/short homozygotes also had higher extraversion. In the face of environmental adversity, females with a short allele had higher scores of neuroticism, anxiety, and depressiveness compared to the l/l genotype. Males were more sensitive to environmental conditions when they had the l/l genotype and low extraversion. In conclusion, the NOS1 ex1f-VNTR influences personality and emotional regulation dependent on gender and environment. Together with previous findings on the effect of the NOS1 genotype on impulse control, these data suggest that NOS1 should be considered another plasticity gene, because its variants are associated with different coping strategies.

Relationship between low depressiveness and domain specific physical activity in women.

In this study we investigated how different domains of physical activity are associated with depressiveness among women, and how individual variables moderate this relationship. Participants were 956 women, and the data were collected by mail-out survey using the Global Physical Activity Questionnaire, Beck Depression Inventory, and International Personality Item Pool. Lower depressiveness was related to higher leisure time physical activity and to lower occupational physical activity. Income, health problems, level of neuroticism, and extraversion had strong effects on depressiveness, and mediated the link between the leisure and occupational activities and depression.

Neuropeptide S receptor gene variant and environment: contribution to alcohol use disorders and alcohol consumption

The functional polymorphism Asn107Ile (rs324981, A > T) of the neuropeptide S receptor (NPSR1) gene is involved in the modulation of traits that affect alcohol use. Hence, we have examined whether the NPSR1 A/T polymorphism is associated with alcohol use disorders (AUD) and alcohol use in a population‐representative sample. Lifetime AUD were assessed by the MINI psychiatric interview (n = 501) in the older cohort of the longitudinal Estonian Children Personality Behaviour and Health Study at age 25. Alcohol use, environmental adversities and personality were reported by both the younger (original n = 583) and the older cohort (original n = 593) in three study waves. NPSR1 associations with AUD and alcohol use differed by sex. In females, both AUD [odds ratio (OR) = 7.20 (0.94–55.0), P = 0.029] and harmful alcohol use were more prevalent in A‐allele carriers. In contrast, in males, AUD was more frequent in T‐allele carriers [OR = 2.75 (1.19–6.36), P = 0.017], especially if exposed to adverse environments at age 15 [OR = 10 (1.18–84.51), P = 0.019]. Alcohol use was higher in male T‐allele carriers at ages 15 and 18 as well. Similarly to females, however, the risk allele for higher alcohol use for males at age 25 was the A‐allele. Many of the effects on alcohol use were explained by genotype effects on measures of personality. In the general population, the NPSR1 Asn107Ile polymorphism is associated with AUD and alcohol consumption, dependent on sex, environment and age. The results are in line with the impulsivity and personality regulating role of the NPSR1.