Andrzej Rajewski

The 5-HT2A -1438 A/G and 5-HTTLPR polymorphisms and personality dimensions in adolescent anorexia nervosa: association study.

Disturbances of serotonergic neurotransmission and temperamental vulnerability have both been implicated in the pathogenesis of anorexia nervosa (AN). We genotyped the –1438 A/G polymorphism in the 5-HT2A receptor gene and serotonin transporter linked-polymorphic region (5-HTTLPR) in 132 adolescent subjects with AN and in 93 healthy controls. Personality dimensions in AN patients were assessed with the Temperament and Character Inventory. In a case-control model, we tested the hypothesis that these genetic variants confer susceptibility to AN. We also analyzed whether two polymorphisms show association with temperamental and character traits. No significant difference was found in the 5-HTTLPR frequency between AN patients and controls; however, there was a statistical trend towards a higher frequency of the A allele of the –1438 A/G polymorphism in patients than in controls (64.9 vs. 56.7%, χ2 test, p = 0.08). We also found a significant association between the A allele of this polymorphism and two temperamental traits. Patients homozygous for the A allele showed lower reward dependence than G/G homozygotes, and A/A homozygotes showed lower harm avoidance than heterozygotes. Low reward dependence and harm avoidance were more characteristic of the restrictive-type AN than of other subtypes of the disorder. No association of 5-HTTLPR with personality dimensions in AN patients was observed. Our results may suggest that the A allele of the –1438 A/G polymorphism confers some genetic risk for adolescent AN patients, especially in those with personality traits, which are typical of the restrictive-type AN.

Serum Neurotrophin Concentrations in Polish Adolescent Girls with Anorexia Nervosa

Objectives: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behaviors as well as in the activity-dependent neuroplasticity underlying learning and memory behaviors involving the hippocampus. In anorexia nervosa (AN) patients, abnormal serum BDNF concentrations, cognitive impairments and specific personality traits have been traditionally observed. This study explores the levels of four serum neurotrophins [BDNF, neurotrophin 3 (NTF3), neurotrophin 4 (NTF4) and glial cell line-derived neurotrophic factor (GDNF)] with respect to their use as potential biomarkers for AN. This study also investigates any associations that might exist between serum neurotrophin levels and neurocognitive impairment or personality traits. Methods: Serum neurotrophin concentrations were measured in 60 AN patients (AN group) and 45 healthy controls (HC group). We correlated the serum levels of the four neurotrophins BDNF, NTF3, NTF4 and GDNF and the clinical type of anorexia. We also analyzed the relationship between serum neurotrophin levels and the Beck Depression Inventory, body mass index, executive functions by the Wisconsin Card Sorting test (WCST) and personality dimensions by the Temperament and Character Inventory (TCI) test. Results: Serum NTF4 concentrations were significantly lower when comparing all AN patients (34.7 ± 72.5 pg/ml) or restriction type AN patients (29.1 ± 62.5 pg/ml) with the HC group (58.4 ± 135.8 pg/ml; p = 0.004 and p = 0.005, respectively). A significant correlation (p < 0.005) between BDNF serum levels and patient personality dimensions as measured by the TCI test was observed. Furthermore, significant correlations were observed between NTF4 and GDNF serum levels and executive function as measured by the WCST. Conclusions: These data suggest that NTF4 might serve as a biomarker for AN. Furthermore, BDNF and GDNF serum levels appear to be associated with personality traits and executive function.

Temperament and Character Inventory (TCI) in adolescents with anorexia nervosa

Background: Female patients with anorexia nervosa differ significantly from the control women in various dimensions of personality. Objective: To investigate the personality dimensions measured with the Temperament and Character Inventory (TCI) in adolescent patients with restrictive-type and bulimic/purging-type anorexia nervosa (ANR and ANB, respectively), and contrast them with the results of control females. Methods: Sixty-one patients with anorexia nervosa (36 ANR and 25 ANB) and 60 controls were tested with the TCI. A concomitant assessment of depression, body mass index and age was made to evaluate the possible correlation with personality dimensions. Results: Adolescent ANR patients scored higher in persistence, harm avoidance and cooperativeness, and lower in novelty seeking and self-transcendence than control women. ANB patients scored in the middle between ANR and control females, but differences did not reach the significance level with either group, except for the self-transcendence dimension where they scored significantly higher than those with ANR. Conclusions: The deviations in temperamental profile of adolescent ANR are similar to those reported in adult patients. The ANB adolescent patients with anorexia nervosa show less prominent deviations from the personality of control women. With regard to the character dimension of cooperativeness, adolescents with ANR scored higher than controls, in contrast to the observations in adult patients. This may reflect the effect of illness on the development of character.

The study of candidate genes related to the neurodevelopmental hypothesis of anorexia nervosa: Classical association study versus decision tree

In this research, we conducted a study of genes connected with the neurodevelopmental hypothesis of anorexia nervosa, using classical statistical and data-mining methods to establish a relationship with disease risk and algorithms to identify the best genetic predictors of anorexia nervosa.

Interleukin-6, tumor necrosis factor α and interferon γ in patients with anorexia nervosa

Several factors influence the immune system in Anorexia Nervosa, among them the inadequate supply of the alimentary compounds and disturbances in the neuroendocrine system. The previously reported changes in some cytokines’ concentrations were regarded not only as an effect of the disease but were postulated to be one of the reasons of AN.

Salivary and serum insulin-like growth factor (IGF-1) assays in anorexic patients

Objectives. The purpose of this study was to measure the salivary and serum free IGF-1 concentration of patients with anorexia nervosa (AN) in comparison to an average population. Methods. A controlled clinical trial was designed for an age- and gender-matched group of 121 AN patients and 77 healthy individuals. A clinical examination was made and blood and salivary samples were taken during the acute stage of AN (BMI < 15 kg/m2) in the first week of hospitalization. An enzyme immunoassay (ELISA) suitable for measuring free IGF-1 was used. Results. Anorexic patients had significant reductions in salivary unstimulated flow rate (UFR), pH and free IGF-1 levels in their saliva and serum. Significant correlations between serum IGF-1 and BMI; salivary IGF-1 and UFR and pH were detected. Conclusions. Salivary and serum IGF-1 analyses appear to be a reliable biochemical indicator of malnutrition in AN patients. Measurement of salivary IGF-1 levels would allow new perspectives in monitoring AN in its early stages.

Parotid gland flow activity and inorganic composition in purging bulimic patients treated with fluoxetine

Abstract Objectives. The purpose of this study was to establish whether vomiting bulimic and/or non-bulimic depressive patients, both treated with the serotonin reuptake inhibitor SI-5-HT (fluoxetine), have differing proportions of inorganic components (specifically, sodium, potassium and calcium) in their parotid salivary gland secretions, than in the average population. Methods. A controlled clinical trial was designed for three age-matched female groups: bulimic patients receiving fluoxetine 40 mg/day (n = 33), non-bulimic patients diagnosed with bipolar affective disorder (fluoxetine 20 mg/day, n = 25) and healthy controls (n = 51). Parotid saliva was collected using a Lashley cap while the subjects were at rest. Stimulation was obtained chemically using a 3% citric acid solution, and physically by instructing the subjects to chew on wax pellets. The concentrations of sodium, potassium and calcium ions were measured using the colorimetric photometry method. Results. The bulimic patients had a reduction in flow and sodium and potassium ions in the parotid saliva and non-bulimic patients had a reduction in flow. Deficits in certain components of saliva were shown to be directly related to salivary flow rate. Conclusions. The data suggest that detection of inorganic deficits in parotid saliva might serve as a reliable confirmation of reduction in flow amongst purging bulimic patients treated with fluoxetine.

Flow rates and inorganic composition of whole saliva in purging bulimic patients treated with a fluoxetine

Abstract Objectives. The current study established whether vomiting bulimic and/or non-bulimic depressive patients, both treated with a serotonin reuptake inhibitor (fluoxetine), have changes in their whole salivary secretion and inorganic components: Na+, K+, Ca2+. Methods. From 108 female subjects, namely bulimics (Group B) (fluoxetine: 40 mg/day) (n = 33), non-bulimic depressives (Group D) (fluoxetine: 20 mg/day) (n = 25) and a Group C of 50 healthy controls, unstimulated and stimulated saliva was collected. The concentrations of Na+, K+, Ca2+ were determined by colorimetric photometry method (Effox 5053, Eppendorf, Germany). Results. The bulimic group reported significant lower output in salivary flow and sodium concentration. In the group (D) only flow was lower than in healthy controls but not significant. Conclusion. This study supports the hypothesis that salivary flow is an unreliable indicator of bulimia, the lack of increase in sodium level in stimulated saliva in bulimic subjects could be a more reliable confirmation of the eating disorder.

TNF‐α and intPLA2 genes' polymorphism in anorexia nervosa

Objective: The aim of this study was the assessment of −308G/A tumor necrosis factor (TNF)-α gene polymorphism and intPLA2 gene polymorphism in patients with anorexia nervosa (AN) and healthy controls. Subjects: We studied 91 non-related patients with AN and 144 healthy women (blood donors and students). The mean age of women from study group was 18.22 years (SD ± 3.13 years) and from control group was 31.71 years (SD ± 8.22). Methods: Gene polymorphisms were studied with the use of polymerase chain reaction-restriction fragment length polymorphism method. TNF-α gene polymorphism consists of G/A substitution in −308 promoter region. IntPLA2 gene polymorphism is related to intron 1, in which restrictive region is found and recognized by BanI enzyme. Results: We did not obtain statistically significant differences in the frequency of genotypes and alleles of −308G/A TNF-α polymorphism between the study and control groups (genotypes: P = 0.106, alleles: P = 0.076). We did analogous analysis in the restrictive and bulimic subgroups. We did not observe statistically relevant differences in the frequency of genotypes (P = 0.700) and alleles (P = 0.305). We did not obtain statistically relevant difference in the frequency of genotypes and alleles of intPLA2 gene between the study group and controls (genotypes: P = 0.300, alleles: P = 0.331). We did analogous analysis in both subgroups of AN. We did not observe statistically relevant differences in the frequency of genotypes (P = 0.344) and alleles (P = 0.230). Conclusions: There was no statistically relevant trend for the association between TNF-α polymorphism and AN. We did not find association between studied polymorphism of intPLA2 gene and risk of AN.

The assessment of the impact of anorexia nervosa on the vocal apparatus in adolescent girls - A preliminary report.

BACKGROUND Chronic undernourishment in the course of anorexia nervosa leads to various metabolic and hormonal changes, which translates to the impaired functioning of the majority of systems and internal organs. The impact of eating disorders on the condition of the vocal apparatus has been described in the literature; nevertheless, it concerns mainly bulimia nervosa. OBJECTIVES assessment of the vocal apparatus in adolescent girls diagnosed with anorexia nervosa from the point of view of possible influence on the function and structure of the larynx, low body mass accompanying anorexia, as well as energy deficiency, hormonal and emotional disturbances. MATERIALS AND METHODS The research included 41 girls aged 12-19 years, diagnosed with anorexia, who were assessed for the condition of the vocal apparatus, using the perceptual assessment of voice according to GRBAS scale, videolarynostroboscopy, acoustic assessment, and voice self-assessment in Jacobsons VHI scale (voice handicap index). RESULTS The perceptual assessment of voice using the GRBAS scale revealed that changes in voice were mainly weak, asthenic in nature (70.73%) and there was also the feature of puffing perceived in voice (41.46%). In voice self-assessment with the use of VHI, most subjects seemed to point to changes of voice self-perception in emotional subscale (68%). Videolaryngostroboscopy revealed some features of functional disturbances of voice in more than half of subjects, mainly in the form of hyperfunctional dysphonia (31.78%). The maximal phonation time was significantly shorter, in proportion to duration of the primary disease. In the acoustic analysis, the decrease in the basic frequency F0 and narrowing of the voice scale were observed. 55% of older, post-adolescent patients presented with the structure of the larynx that was inappropriate for their age. CONCLUSIONS These results might indicate that anorexia nervosa could have led to the structural and functional changes in the vocal apparatus. Such disturbances may be explained by the hormonal dysfunctions as well as starvation. Hormonal substitution at the appropriate time might be beneficial for the structure and phonation function of the larynx in girls with AN.