Expression of immune-related proteins and their association with neuropeptides in adolescent patients with anorexia nervosa.

Anorexia nervosa (AN) is a metabo-psychiatric disorder where alterations of cytokines, neuropeptides, neurotransmitters, and the interactions between these factors can play an important role. Thus, the primary goal of the presented study was a cross-sectional analysis of immune-related proteins in patients with AN. Moreover, the correlations between these molecules and selected neuropeptides were studied. Twenty-five adolescent inpatients girls in the acute stage of a restrictive type of AN were enrolled in the study within the first year of the disease. Additionally, thirty similar in age and height controls (CG) were also assessed. The levels of 24 immune-related proteins, including cytokines, chemokines, and proteases, were measured. Moreover, selected adipocytokines, gastrointestinal hormones, and centrally produced neuropeptides levels were determined. Finally, the correlations between these molecules were analyzed. The fasting levels of CXCL1, CXCL9, FGF2, GrB, IL1, IL6, IL8, MMP8, MMP9, CTSS were statistically lower in AN than in the CG. The concentrations of many immune-related proteins remain unchanged despite their metabolic and mental condition. Moreover, significant correlations were found between leptin and CXCL1, CXCL9, GrB, IL1, IL6, and MMP8. Leptin receptors were correlated with GrB, while resistin was associated with MMP9. Our findings suggest that the initial stage of restrictive AN among adolescents within the first year of the disease is not connected with a pro-inflammatory state. Some immune-related protein changes may be associated with altered neuropeptides, primarily leptin, its receptors, and resistin. Future research should clarify which changes are primary and secondary to weight loss and whether these changes normalize with increasing weight. This would aid in understanding the complex etiopathogenesis of AN and in the search for new methods of treatment.

The role of factors associated with the course of pregnancy and childbirth in attention deficit hyperactivity disorder (ADHD). / Rola czynników zwiazanych z przebiegiem ciazy i porodu w zespole nadpobudliwosci psychoruchowej z deficytem uwagi.

OBJECTIVES: Assessment of the prevalence of risk factors associated with the course of pregnancy and childbirth and the condition of the child after birth in agroup of children and adolescents with ADHD and a control group. METHODS: 205 unrelated children and adolescents diagnosed with ADHD and 106 primary and secondary school students aged 7-17. Method. Mothers of children and adolescents diagnosed with ADHD, and those from the control group, were asked to provide a medical history in order to obtain data to supplement the Pregnancy and perinatal history questionnaire. RESULTS: Statistically significant differences (p < 0.05) were demonstrated for the incidence rates of factors related to the course of pregnancy and childbirth such as: the occurrence of maternal diseases during pregnancy, especially in the I/II trimester, and other problems during pregnancy; exposure to stress and taking medication during pregnancy; smoking during pregnancy; mother's age at childbirth, i.e., < 25 years or > 35 years; use of pain reducing substances during labor and problems with the child during the delivery;an APGAR score in the range of 5-7 points; the occurrence of neonatal jaundice necessitating treatment, especially replacement transfusion; physical anomalies or other congenital problems in the newborn, as well as adaptive problems necessitating neonatal oxygen administration or placement in an incubator. CONCLUSIONS: Significantly more frequent occurrence of risk factors related to the course of pregnancy, childbirth and the child's condition after birth in the ADHD group may indicate their potential role in the etiology of ADHD.

Longitudinal study on novel neuropeptides phoenixin, spexin and kisspeptin in adolescent inpatients with anorexia nervosa - association with psychiatric symptoms.

OBJECTIVES: It is hypothesized that novel neuropeptides such as phoenixin (PNX), spexin (SPX), and kisspeptin (KISS) are involved in the pathogenesis of eating disorders. The study presented here analyzed neuropeptide concentrations during the course of anorexia nervosa (AN) and aimed to correlate those values with anthropometric and psychometric measurements. METHODS: A longitudinal study was carried outin 30 AN adolescent patients and 15 age-matched healthy female controls. Selected neuroprotein serum levels were analyzed in malnourished patients (accAN) and following partial weight recovery (norAN), and these values were compared with the control group. RESULTS: In accAN patients, decreased serum PNX levels were detected while SPX serum concentrations were lower in the accAN and norAN patients. No differences were observed in KISS concentrations in all studied groups. CONCLUSIONS: In malnourished adolescent inpatients with AN, serum PNX and SPX level were decreased. The partial weight recovery normalized PNX concentrations but failed to normalize SPX levels. Therefore these two neuropeptides might be crucial for the etiology and course of the AN. The KISS levels did not change in the course of AN. The PNX levels were associated with some symptoms of eating disorders which may indicate its potential contribution in the regulation of emotions and behaviors in AN.

Adiponectin and resistin in acutely ill and weight-recovered adolescent anorexia nervosa: Association with psychiatric symptoms.

Objectives: Anorexia nervosa (AN) is a chronic illness where restriction of food intake results in decreased adipose tissue. The aim of this study was to measure the concentration of adiponectin and resistin in acute and partially weight-recovered anorectic inpatients. The associations of their levels with eating disorder symptoms were also assessed.Methods: A longitudinal study was conducted on 76 adolescent patients (ANG) and 30 age-matched healthy girls (CG). Selected adipokines serum levels, as well as the severity of depressive, obsessive-compulsive and disturbed eating behaviours, were analysed in the group of anorectic patients before (accAN) and after weight gain (recAN) and compared with the CG.Results: The concentration of adiponectin in the accAN was higher than in the CG (P = 0.05) and increased in recAN (P = 0.01). Resistin concentrations were lower in accAN and recAN than in the CG (P = 0.00). A negative correlation between adiponectin and the scores in Yale-Brown Obsessive Compulsive Scale as well as positive between resistin and Beck Depression Inventory were found.Conclusions: In the acute AN, adiponectin and resistin levels are impaired and partial weight recovery fails to normalise them thus we suggest that they can be involved in the chronicity of certain symptoms. The level of adiponectin is associated with obsessive and compulsive symptoms and resistin with depressive symptoms, which indicates their potential contribution to the regulation of emotions and behaviours in AN.

The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women.

OBJECTIVE: The aim of the study was assessment of a possible relationship between the polymorphisms of the candidate genes participating in the etiology of some neurological and psychiatric disorders and the risk of depression in perimenopausal and postmenopausal women. METHODS: A total of 167 (54 perimenopausal and 113 postmenopausal) Caucasian women from western Poland, aged 42-67, were recruited as the patient group in the study because of depressive symptoms, and another 321 healthy women (102 perimenopausal and 219 postmenopausal) served as the controls. All study participants were evaluated for climacteric and depressive disorders according to the Kupperman index and Hamilton rating scale for depression (HRSD), respectively. The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1. In each group the frequencies of the polymorphisms were determined using PCR-RFLP analysis. RESULTS: After correcting for Bonferroni multiple tests, we found associations between the MAOA c.1460C>T (SNP 1137070), COMT c.472G>A (SNP 4680), MTHFR c.677C>T (SNP 1801133) and ESR1 454(-351) A>G (SNP 9340799) polymorphisms to mild and moderate depressive symptoms in menopausal women. In the perimenopausal and postmenopausal women, genotype association of the MAOA c.1460 CT and c.1460 CT+TT (OR=1.83; pcorr=0.009 and OR=1.85; pcorr=0.003, resp.), and of the MTHFR c.677 TT and c.677 CT+TT (OR=3.52; pcorr=0.00009 and OR=2.06; pcorr=0.0006, resp.), as well as of the COMT c.472 GA and COMT c.472 GA+AA genotypes (OR=2.23; pcorr=0.03 and OR=2.17; pcorr=0.027, resp.) in the postmenopausal women revealed significantly higher frequencies of these variants in depressed female patients than in controls, whereas the ESR1 454(-351) AG and 454(-351) AG+GG genotypes were associated with lower risk of depression in postmenopausal women (OR=0.48; pcorr=0.012, and OR=0.52; pcorr=0.015, resp.). CONCLUSIONS: Our study substantiates the involvement of the MAOA and MTHFR polymorphisms in climacteric depression and offers evidence that the COMT and ESR1 genes may also play a role in the susceptibility to depressive mood in postmenopausal women.

Disturbances of sleep continuity in women during the menopausal transition.

OBJECTIVES: The objective of the study was to evaluate the prevalence of sleep continuity disorders in women during menopausal transition, to evaluate the relationship between disturbances of sleep continuity and the severity of menopausal syndrome and the occurrence of various symptoms of this syndrome, as well as to evaluate the association between the presence of sleep disturbances and serum concentrations of gonadotropins, prolactin and sex hormones. METHODS: Consecutive 140 women (mean age 54.4 ± 4.7 years) searching for the treatment in the Clinic for Gynaecological Endocrinology who reported symptoms of menopausal syndrome were investigated. The type and severity of disturbances of sleep continuity were evaluated using a survey based on the sleep related questions from Hamilton Depression Rating Scale. The severity of symptoms of menopausal syndrome was assessed using the Kupperman Index. The concentration of the following hormones in blood serum was tested: FSH, LH, 17ß-estradiol, PRL, total testosterone, DHEAS and SHBG. RESULTS: Disturbances of sleep continuity were a prevalent complaint in the studied group of women. Difficulties in falling asleep were found in 57.8% of women, difficulties in maintaining sleep in 70%, waking up too early in 60.7%. The severity of all three types of sleep continuity disturbances was related to the severity of menopausal syndrome as measured with Kupperman Index (Spearman correlation coefficient r = 0.63, r = 0.61, r = 0.52, respectively; p < 0.001). Difficulties in maintaining sleep were negatively correlated with the concentration of FSH (r = - 0.19; p < 0.05), 17ß-estradiol (r = - 0.19; p < 0.05) and SHBG (r = - 0.18; p < 0.05), difficulties in falling asleep negatively correlated with the concentration of 17ß-estradiol in the blood serum (r = - 0.19; p < 0.05). CONCLUSIONS: Sleep continuity disturbances are frequently reported by women during the menopausal transition. Interventions aimed at reducing the symptoms of menopausal syndrome should be considered as important action to improve sleep quality in this population of patients.

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.

Association of tumor necrosis factor -308G/A promoter polymorphism with schizophrenia and bipolar affective disorder in a Polish population.

BACKGROUND/AIMS: Schizophrenia (SCH) and bipolar affective disorder (BPAD) are complex disorders with significant participation of genetic risk factors. Several lines of evidence point to the role of shared neurobiological mechanisms and common genetic background in SCH and BPAD. Immune disturbances have been suggested as contributing factor in the pathogenesis of both SCH and BPAD. The gene coding cytokine tumor necrosis factor (TNF) has been the object of a number of association studies in SCH, with ambiguous results. Only 3 such studies were performed in BPAD. The aim of our study was to perform a case-control association analysis of the TNF -308G/A polymorphism in a Polish sample of patients with SCH, BPAD and healthy controls. METHODS: We genotyped the TNF -308G/A polymorphism (rs1800629) by PCR-RFLP in 348 patients with SCH, 361 patients with BPAD and in 351 controls. RESULTS: We observed an association of the -308G allele with both SCH (p = 0.008) and BPAD (p = 0.039), and also with a positive family history in patients with SCH (p = 0.048) and BPAD (p = 0.027). For TNF genotypes, the association was only seen in SCH (p = 0.018). CONCLUSIONS: Our results may point to an association of the TNF -308G allele and -308G/G genotype with both SCH and BPAD, and to a relationship of the -308G allele with the risk of SCH and BPAD in patients with a positive family history. TNF could be potentially a susceptibility gene, shared between SCH and BPAD. Complex TNF gene studies--based on multiple single-nucleotide polymorphisms and involving haplotype analysis--are necessary for the clarification of currently contradictory findings.

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.