Kirsti Akkermann

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.

Food restriction leads to binge eating dependent upon the effect of the brain-derived neurotrophic factor Val66Met polymorphism.

Brain-derived neurotrophic factor (BDNF) regulates food intake and energy metabolism. It has also been suggested that mutations in the human BDNF gene and its receptor TrkB account for disturbed eating and obesity. The Met-allele of the BDNF Val66Met polymorphism has been associated with eating disorders, but the underlying mechanism of its contribution is not known. We report herewith that the effect of BDNF Val66Met polymorphism on binge eating in adolescent girls is dependent on severe food restriction. The scores on EDI-2 Bulimia subscale were significantly higher in BDNF Met-allele carriers who made attempts to regulate their body weight by reducing their meal frequency or by starving. This finding may help to explain why some people develop binge eating in response to dieting and others do not.

Serotonin transporter gene promoter polymorphism affects the severity of binge eating in general population.

OBJECTIVE The s-allele of the 5-HTTLPR has been suggested to lead to the development of less efficient and less flexible 5-HT system and has been associated to different forms of psychopathology. It has also been shown that alterations in serotonergic activity contribute to the pathophysiology of binge eating but it is not clear which changes in 5-HT function observed in eating disorder patients represent trait vs state effect. We investigated the association between the 5-HTTLPR and binge eating in a population-representative sample of women, and tested whether the 5-HTTLPR genotype influences the severity of binge eating. METHODS The sample was based on women participating in the third wave of the Estonian Children Personality, Behaviour and Health Study. EDI-2 subscales - drive for thinness and bulimia - were used to assess eating behaviour and attitudes. Barratt Impulsiveness Scale (BIS-11) and State and Trait Anxiety Inventory (STAI) were used to measure impulsivity and anxiety. Participants were genotyped for the 5-HTTLPR. RESULTS There was no 5-HTTLPR genotype effect on binge eating even after the covarying effect of impulsivity and anxiety was controlled for. However, women prone to binge eating and carrying the s-allele showed significantly higher levels of bulimia scores, and among them, women with s/s genotype had also higher levels of state anxiety and tendency for higher impulsivity. CONCLUSIONS While the 5-HTTLPR genotype does not predict symptoms of eating disorder in general population, the s-allele, and especially the s/s genotype increases the risk for affective instability and symptom severity.

Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders.

OBJECTIVE Caseinolytic protease B (ClpB) produced by Enterobacteria, such as Escherichia coli, has been identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic and anxiogenic neuropeptide. In mice, ClpB induces α-MSH cross-reactive antibodies and activates anorexigenic brain neurons. In patients with eating disorders (ED), anti-ClpB and anti-α-MSH antibodies correlate with psychopathological traits. However, it is not known if ClpB is present in human plasma including ED patients. METHODS Plasma concentrations of ClpB were measured using a recently developed ClpB immunoassay in female patients with anorexia nervosa, bulimia nervosa, and binge-eating disorder and compared with healthy participants, all characterized by the Eating Disorder Inventory-2 (EDI-2) scale. RESULTS We found that ClpB was readably detectable in plasma of healthy participants and ED patients and that its concentrations were elevated in ED patients, without significant differences in patients subgroups. Plasma ClpB concentrations correlated with the EDI-2 scores, with α-MSH as well as with plasma levels of anti-ClpB and anti-α-MSH antibodies. DISCUSSION These data revealed that bacterial ClpB is naturally present in human plasma and that its concentrations can be elevated in ED patients and associated with ED-related psychopathological traits. These results support a link between bacterial ClpB and the ED pathophysiology.

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.

Association of 5‐HTT gene polymorphism, platelet MAO activity, and drive for thinness in a population‐based sample of adolescent girls

OBJECTIVE Several lines of evidence suggest that alterations in serotonergic activity contribute to the pathophysiology of abnormal eating behaviors. Since platelet monoamine oxidase (MAO) activity and the 5-HT transporter gene promoter polymorphism (5-HTTLPR) have been associated with eating disorders, the knowledge from a population-based sample may provide useful information which changes in 5-HT function observed in eating disorders represent trait vs. state effects. METHOD The sample was based on both cohorts of the Estonian Children Personality, Behavior and Health Study (ECPBHS). The current study was conducted during the second follow-up where altogether 82% from the original sample was recruited. EDI-2 subscales--Drive for Thinness and Bulimia--were used to determine eating attitudes and behaviors. Platelet MAO activity was measured and the participants were genotyped for the 5-HTTLPR. RESULTS Allelic variation of 5-HTTLPR or platelet MAO activity were not independently associated with drive for thinness or binge eating, but girls homozygous for the 5-HTTLPR long allele and with high platelet MAO activity, both considered indicators of a higher capacity 5-HT system, exhibited higher scores of drive for thinness. CONCLUSION The results suggest that drive for thinness is the highest in girls with the presence of two markers of higher serotonergic capacity.

Effect of COMT Val158Met polymorphism on personality traits and educational attainment in a longitudinal population representative study

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, Bonferroni-corrected for five traits). By the age 25, males with the Val/Met genotype had mainly secondary or vocational education, whereas female heterozygotes mostly had obtained or were obtaining university education. COMT Val158Met was not associated with anxiety or mood disorders in either gender. These results suggest that genes affecting dopamine system are involved in the development of personality traits and contribute to educational attainment.

Mitigating aggressiveness through education? The monoamine oxidase A genotype and mental health in general population

Objective Monoamine oxidase A (MAOA) gene promoter region includes a variable number of tandem repeat (VNTR) associated with antisocial behaviour in adverse environment. We have examined the effect of the MAOA-uVNTR on mental health and academic success by using a population representative sample and a longitudinal design. Methods The data of the older cohort (n = 593, aged 15 years at the original sampling) of the longitudinal Estonian Children Personality, Behaviour and Health Study (ECPBHS) were used. Follow-ups were conducted at ages 18 and 25 years. Aggressiveness, inattention and hyperactivity were reported by class teachers or, at older age, self-reported. Stressful life events, psychological environment in the family and interactions between family members were self-reported. Data of general mental abilities and education were obtained at the age of 25, and lifetime psychiatric disorder assessment was carried out with the Mini-International Neuropsychiatric Interview (MINI) interview. Results MAOA-uVNTR genotype had no independent effect on aggressiveness, hyperactive and inattentive symptoms, and neither was there a genotype interaction with adverse life events. Interestingly, the proportion of male subjects with higher education by the age of 25 was significantly larger among those with MAOA low-activity alleles (χ2 = 7.13; p = 0.008). Logistic regression revealed that MAOA low-activity alleles, higher mental abilities, occurrence of anxiety disorders and absence of substance-use disorder were significant independent predictors for higher education in male subjects. Conclusions In a population representative sample of young subjects, the MAOA-uVNTR ‘risk genotype’ predicted better life outcomes as expressed in higher level of education.

Fluctuations in negative emotions predict binge eating both in women and men: An experience sampling study

ABSTRACT This study investigated the associations between emotional fluctuations and emotion regulation difficulties in predicting binge eating and overeating episodes using the experience sampling method among 97 women and 61 men. Among women, fluctuations in negative emotion, emotion regulation difficulties, restrained eating, and the interaction of negative emotion fluctuations and emotion regulation difficulties predicted binge eating. Among men, trait impulsivity and fluctuations in negative emotion predicted binge eating. However, overeating did not associate with aforementioned aspects. Results suggest that fluctuations in negative emotions should be studied in the context of emotion regulation difficulties.

Fears in the General Population More Frequent in Females and Associated With the Serotonin Transporter Promoter Polymorphism and Perceived Relationship With Mothers

This study aimed to examine the structure of fears of youth, and its associations with gender, genetic variation of the serotonin transporter (5-HTTLPR), and perceived maternal acceptance/rejection and control, in a population-representative sample. Participants were 453 adolescents and 540 young adults. Fears were assessed by a 18-item Fear Questionnaire, and perceived maternal relationships by the Mother Acceptance-Rejection/Control Questionnaire. A structured psychiatric interview was used to assess current and lifetime psychiatric disorders in participants from the older cohort. A principal component analyses indicated 2 components, named Fear/Phobia and Panic/Despair. Females expressed higher level of fears and symptoms of despair regardless of the serotonin transporter genotype. The 5-HTTLPR genotype nevertheless played a role in the association between fears and perceived relationships: in S/S-genotype, more Fear/Phobia was reported by the participants who perceived greater maternal acceptance in combination with strict maternal control, and had a history of psychiatric disorder.