OPRM1 Gene Polymorphism in Women with Alcohol Use Disorder.

The main aims of the present study were to explore the relationship of the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women with their personality traits and to try to find out whether any specific features may influence alcohol cravings and be a prognostic for alcohol dependency and treatment in AUD women. Our study found a notable correlation between openness and the interaction of the ORIM1 gene and AUD. The alcohol use disorder subjects with genotype AG showed a higher level of openness compared to the control group with genotypes AG (p = 0.0001) and AA (p = 0.0125). The alcohol use disorder subjects with the AA genotype displayed higher levels of openness than the control group with genotype AG (p = 0.0271). However, the alcohol use disorder subjects with the AA genotype displayed lower levels of openness than the control group with genotype GG (p = 0.0212). Our study indicates that openness as a personality trait is correlated with the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women. These are the first data and results exploring such a relationship between opioid and alcohol pathways and the mental construction of AUD women. Personality traits such as openness to experience and neuroticism might play major roles in the addiction mechanism, especially in genetically predisposed females, independent of the reward system involved in the emotional disturbances that coexist with anxiety and depression.

Association between Psychopathological Symptoms and Aggression and Selected Biochemical Parameters in Adolescents with Behavioural and Emotional Disturbances.

Behavioural and emotional disturbances (F92.8) are the most recognized disorders in a developmental psychiatry. As the problem is still alarmingly increasing, the searches for their etiopathogenesis and more effective preventing and therapy methods are required. The aim of the study was to assess the association between the quality of life, some psychopathological features, concentrations of selected immunoprotective (brain-derived neurotrophin, BDNF), and endocrine (cortisol, F) factors while adolescent disturbances. The study was performed in 123 inpatients of a psychiatric ward with F92.8 diagnosis, aged 13-18 years. The complete patients' interview, physical examination, and routine laboratory tests, including serum F and BDNF tests, were performed. All patients completed standardized questionnaires to estimate: the severity of psychopathological symptoms (SCL-90), the level of aggression (Buss-Perry). The changes in the plasma BDNF and F concentrations were shown in patients raised in foster homes and institutions. The significantly lower BDNF was observed in youth from foster and suicide-experienced families. The more severe psychopathological symptoms, especially aggression and hostility, were found in these ones, who abused alcohol, attempted suicide, had lower self-esteem and cognitive processes, and were lacking safety in dysfunctional families.

Cannabis and cannabinoids: pharmacology and therapeutic potential.

INTRODUCTION: Cannabis (also known as marijuana) is the most frequently used psychoactive substance in the world. The role of cannabis in medicine is rapidly evolving, and advances in the understanding of its pharmacology have led to numerous proposed uses of these drugs. STATE OF THE ART: Cannabis contains Δ9-tetrahydrocannabinol and cannabidiol as the primary constituents responsible for pharmacological activity. It is now known that there are at least two types of cannabinoid receptors. CB1 receptors are found mainly in the CNS, and their primary role is to inhibit the release of neurotransmitters. CB2 receptors' leading role is to modulate cytokine release and immune cell migration. Colocalisation of cannabinoid receptors with other types of nervous system receptors allows them to interact with many other transmitters such as dopamine, noradrenaline, acetylcholine, gamma-aminobutyric acid, serotonin, and glutamic and aspartic acids. CLINICAL IMPLICATIONS: The rapidly expanding understanding regarding cannabinoids led to initial attempts to treat selected diseases with cannabinoid receptor agonists and antagonists. The most promising of these was the potential possibility of treating diseases for which current therapy is unsatisfactory, such as neurological diseases including multiple sclerosis, spastic muscular tension, extrapyramidal system diseases, neurodegenerative diseases and cerebral ischaemia. Attempts to treat psychiatric diseases (e.g. psychoses, neuroses, mood disorders, and alcohol dependence syndrome) with cannabinoids are much less advanced. FUTURE DIRECTIONS: Cannabis and cannabinoids can be widely used to treat several diseases or alleviate symptoms, but their efficacy for specific indications is not always apparent. Further exploration is needed to understand whether the enhanced sensitivity to the cognitive effects of Δ9-THC depends on brain cannabinoid receptor dysfunction, and how these changes contribute to the cognitive deterioration and core pathophysiology symptoms associated with schizophrenia or other neurological and somatoform disorders.

Association of plasma hormones, nutritional status, and stressful life events in anorexia nervosa patients.

OBJECTIVE: The aim of the current study was to analyze the relationships between plasma hormones, body weight parameters and stressful life events in anorexia nervosa (AN). MATERIAL AND METHODS: 72 females in the active phase of AN were evaluated. 52 healthy women constituted the control group. RIA kits were used to measure plasma hormone levels. RESULTS: The concentrations of leptin, insulin, IGF-1, triiodothyronine, LH, FSH, estradiol, and testosterone were significantly lower and those of cortisol and growth hormone significantly higher in the AN than the control group. No hormonal differences between restrictive and binge-purging AN subtypes were found. Leptin, IGF-1, gonadotropins, and sex steroids correlated significantly negatively and growth hormone positively with total reduction of body weight or the degree of undernutrition. Associations were also found between lower insulin concentration and family violence, lower cortisol and psychiatric diseases in the family, higher testosterone and patient's alcohol or drug abuse. DISCUSSION: The changed activity of the somatotropin-somatomedin, gonadal, and corticotrophin axes corresponds to the clinical stage of AN. Plasma IGF-1 seems to be the most sensitive and useful independent hormonal marker of cachexia.

Significance of Selected Environmental and Biological Factors on the Risk of FASD in Women Who Drink Alcohol during Pregnancy.

Prenatal alcohol exposure (PAE), which refers to alcohol consumption by pregnant women, is associated with the risk of numerous severe complications during fetal development. The State Agency for Alcohol Problem Solving reports that the incidence of fetal alcohol spectrum disorder (FASD) in Poland's general population is over 1.7%, and the incidence of fetal alcohol syndrome (FAS) is estimated at more than 0.5%. This study aimed to evaluate the significance of alcohol exposure and focused on the pattern of alcohol intoxication exhibited by the mother during pregnancy and other environmental factors of the maternal environment contributing to the development of FASD. The study covered 554 subjects, including 251 mothers and 303 children (213 girls and 90 boys). The mother's drinking problem was determined based on the information obtained from the case history. All children qualified for the study fulfilled the h-PAE (high alcohol exposure) criteria during their fetal life. The clinical diagnosis of FAS and pFAS (occurrence of morphological symptoms of fetal alcohol syndrome) was made using a four-digit diagnostic questionnaire validated in the Polish version of the Washington Questionnaire for the assessment of the spectrum of alcohol-related neurodevelopmental disorders or alcohol-related cognitive impairment (ARND/C). Statistical analysis of the obtained research results was developed using statistical software-STATISTICA PL, version 13.1 (StatSoft, Inc., Szczecin, Poland 2016, STATISTICA-data analysis software system, version 13.1). The most destructive drinking behaviors are compulsive intoxication (BD, binge drinking) during the first 6 weeks of pregnancy and chronic addiction throughout its duration (CHD, chronic drinking). Chronic alcohol intoxication (CHD) leads to a poorer nutritional status in mothers, which is reflected in a lower body mass index (BMI) (<18 kg/m2).

Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

Associations between the COMT rs4680 Gene Polymorphism and Personality Dimensions and Anxiety in Patients with a Diagnosis of Other Stimulants Dependence.

BACKGROUND: Research on the hypodopaminergic hypothesis of addictions showed that hypodopaminergic activity in males predicted the number of drugs used and is associated with drug-seeking behavior. Variant alleles may cause hypodopaminergic functioning as a result of the reduced density of dopamine receptors, decreased response to dopamine, increased dopamine clearance or metabolism in the reward system. The catechol-O-methyltransferase (COMT) is involved in the metabolism of dopamine. Personality traits may mediate the genetic predisposition to substance use disorders additively by various motivations associated with reward-seeking and regulating negative emotions, and also relate to self-control and environment selection. THE AIM OF THE STUDY: The aim of this study was to investigate the association of the rs4680 polymorphism of COMT with personality dimensions and anxiety in patients addicted to stimulants other than cocaine (F15 according to WHO ICD-10 nomenclature) in the case of examined patients amphetamine. METHODS: The study was conducted among patients addicted to stimulants other than cocaine (amphetamine). The study group included 247 patients addicted to stimulants (amphetamine) and the control group comprised 280 healthy male volunteers. The real-time PCR method was used to carry out genetic tests; personality dimensions were assessed using the standardized NEO-FFI and state and trait anxiety were assessed with STAI. All analyses were performed using STATISTICA 13. RESULTS: The results of the 2 × 3 factorial ANOVA showed a statistically significant effect of the combined factor COMT rs4680 genotype on the group of patients diagnosed with other stimulants dependence/control (F2,252 = 3.11, p = 0.0465, η2 = 0.024). Additionally, we observed that the results of the 2 × 3 factorial ANOVA showed a statistically significant influence of the combined factor COMT rs4680 on the genotype in the group of patients diagnosis with other stimulants dependence/control (F2,252 = 6.16, p = 0.0024, η2 = 0.047). CONCLUSIONS: In our research, the polymorphism G/G COMT rs4680 genotype was associated with higher scores of STAI traits and STAI states in the patients dependent on amphetamine. In the control group we observed no such interactions.

Association between Polymorphism rs1799732 of DRD2 Dopamine Receptor Gene and Personality Traits among Cannabis Dependency.

Compared to other addictive substances, patients with cannabis addiction are significantly outnumbered by those who report dependence on other, more addictive substances. Unfortunately, most cannabis addiction goes untreated, and among those who choose treatment, the requirements are much higher for adolescents and young adults. THE AIM OF THE STUDY: To examine the relationship of cannabinoid dependency in the genetic context-the association between the rs1799732 polymorphism of the DRD2 gene and psychological traits and anxiety. METHODS: The study group consisted of 515 male volunteers. Of these, 214 patients were diagnosed with cannabis addiction and 301 were non-addicted. Patients were diagnosed with NEO Five-Factor Personality Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI) questionnaires. The interactions between personality traits and polymorphisms in the DRD2 rs1799732 gene were investigated in a group of cannabis-addicted patients and non-addicted controls using the real-time PCR method. RESULTS: Compared to the control group, the case group obtained significantly higher scores on the STAI State, STAI Trait, Neuroticism and Openness scales, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness scales. There was no statistically significant difference between addicts and the control group in the frequency of genotypes, but there was a statistically significant difference between addicts and the control group in the frequency of the DRD2 allele rs179973. The multivariate ANOVA analysis showed a statistically significant influence of the DRD2 rs1799732 genotype on the NEO-FFI agreeableness scale and a statistically significant effect of addiction to cannabinoids or its absence on the NEO-FFI agreeableness scale score. CONCLUSIONS: Studying homogeneous subgroups-as in our study-seems reasonable, particularly when combined with genetic determinants and psychological traits. In multigenic and multifactorial entities, such a strategy has a future.

Methylation in the Promoter Region of the Dopamine Transporter DAT1 Gene in People Addicted to Nicotine.

The dopaminergic system is a crucial element of the addiction processes. The dopamine transporter modulates the dynamics and levels of released dopamine in the synaptic cleft. Therefore, regulation of dopamine transporter (DAT1) gene expression is critical for maintaining homeostasis in the dopaminergic system. The aim of our study is evaluation of the methylation status of 33 CpG islands located in the DAT1 gene promoter region related to nicotine dependency. We investigated 142 nicotine-dependent subjects and 238 controls. Our results show that as many as 14 of the 33 CpG islands tested had statistically significantly higher methylation in the nicotine-dependent group compared to the control group. After applying Bonferroni correction, the total number of methylation sites was also significantly higher in the dependent subjects group. The analysis of the methylation status of particular CpG sites revealed a new direction of research regarding the biological aspects of nicotine addiction.

Association of Polymorphism within the Putative miRNA Target Site in the 3'UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder.

The study aims at looking into associations between the polymorphism rs6276 that occurs in the putative miRNA target site in the 3'UTR region of the DRD2 gene in patients with substance use disorder (SUD) comorbid with a maniacal syndrome (SUD MANIA). In our study, we did not state any essential difference in DRD2 rs6276 genotype frequencies in the studied samples of SUD MANIA, SUD, and control subjects. A significant result was found for the SUD MANIA group vs. SUD vs. controls on the Neuroticism Scale of NEO FFI test, and DRD2 rs6276 (p = 0.0320) accounted for 1.7% of the variance. The G/G homozygous variants were linked with lower results on the neuroticism scale in the SUD MANIA group because G/G alleles may serve a protective role in the expression of neuroticism in patients with SUD MANIA. So far, there have been no data in the literature on the relationship between the miRSNP rs6276 region in the DRD2 gene and neuroticism (personal traits) in patients with a diagnosis of substance use disorder comorbid with the affective, maniacal type disturbances related to SUD. This is the first report on this topic.

Association of Polymorphism CHRNA5 and CHRNA3 Gene in People Addicted to Nicotine.

Smoking is a chronic and relapsing addictive trait that harms public health. Among the many identified genetic variants of nicotine dependence, the variants in the CHRNA5/A3/B4 gene cluster on chromosome 15 that encode the α5, α3, and ß4 subunits have recently received a lot of attention. Importantly, variants in this gene cluster have been associated with nicotine addiction. Among the many significant variants in this cluster, the polymorphism SNP rs16969968 seems to be the most interesting factor in nicotine addiction. This polymorphism causes an amino acid change from aspartate to asparagine at position 398 of the α5 nicotinic receptor protein sequence. Our study aimed to analyze three polymorphic variants: the rs16969968 located in the CHRNA5 gene, the rs578776 and rs1051730 located in the CHRNA3 gene in nicotine-addicted subjects, and in controls. Our study encompasses an association analysis of genotypes and haplotypes. A group of 401 volunteers was recruited for the study and divided into two groups: the study group consisted of addicted smokers and a control group of 200 unrelated non-smokers who were not dependent on any substance and healthy. A statistically significant difference was observed in the frequency of genotypes of the rs1051730 polymorphism of the CHRNA3 gene (χ2 = 6.704 p = 0.035). The T/T genotype was statistically significantly more frequent in the group of nicotine-dependent subjects. The haplotypes rs16969968, rs578776, and rs1051730 were distinguished, of which the G-T-T and G-C-T haplotypes were present only in the study group. With differences in frequencies, statistical significance was noted-for the G-T-T haplotype p = 0.01284 and the G-C-T haplotype p = 0.00775. The research stated that novel haplotypes G-T-T and G-C-T, though with very low-frequency variants in CHRNA3, were associated with nicotine addiction.

DRD4 Exon 3 Gene Polymorphisms in Patients Diagnosed with Polysubstance Use Disorder and Co-Occurrence of a Depressive Episode.

BACKGROUND: There has been a noticeable and systematic growth of the use of psychoactive substances over the past few decades. Dual diagnosis is a clinical term referring to the occurrence of psychoactive substance use disorder comorbid with another psychiatric disorder in the same person. The most common type of dual diagnosis is the co-occurrence of alcohol use disorder and mood disorders in the form of a depressive episode. Co-occurrent substance use disorders are frequently influenced by genetic factors. In selecting our area of research, we focused on dopamine and the DRD4 (Dopamine Receptor D4) gene polymorphism as well as associations with personality features. THE AIM OF THE STUDY: The aim of the study was to compare DRD4 exon 3 (DRD4 Ex3) gene polymorphisms in patients diagnosed with polysubstance use disorder and co-occurrence of a depressive episode to DRD4 exon 3 gene polymorphisms in patients diagnosed with polysubstance use disorder and without co-occurrence of a depressive episode and a group of healthy volunteers. The study also aimed at establishing associations between personality features and DRD4 exon 3 gene polymorphisms of male patients diagnosed with polysubstance use disorder with co-occurrence of a depressive episode which may present a specific endophenotype of this group of patients. METHODS: The study group comprised 602 male volunteers: patients diagnosed with polysubstance use disorder comorbid with a depressive episode (PUD MDD) (n = 95; mean age = 28.29, standard deviation (SD) = 7.40), patients diagnosed with polysubstance use disorder (PUD) (n = 206; mean age = 28.13, SD = 5.97), and controls (n = 301; mean age = 22.13, SD = 4.57). The patients and control subjects were diagnosed by a psychiatrist using the Mini International Neuropsychiatric Interview (MINI), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) questionnaires. An analysis of the DRD4 exon 3 polymorphism was performed. RESULTS: The patients diagnosed with PUD MDD compared to the control group of healthy volunteers showed significantly higher scores on both the STAI status and features scale and the NEO-FFI Neuroticism and Openness Scale, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness NEO-FFI scales. In the DRD4 exon 3 gene polymorphism, the s allele was more frequent in the PUD MDD compared to the l allele, which was less frequent. The results of the 2 × 3 factor analysis of variance (ANOVA) in patients and controls and the variant DRD4 exon 3 interaction were found on the Extraversion Scale and the Conscientiousness Scale of the NEO-FFI. CONCLUSIONS: The associations show that psychological factors combined with genetic data create a new area of research on addiction, including the problem of dual diagnosis. However, we want to be careful and draw no definite conclusions at this stage of our research.

[Temperament and character of Polish women with anorexia and bulimia nervosa]. / Analiza wymiarów temperamentu i charakteru u doroslych kobiet z zaburzeniami odzywiania sie.

AIM: One of the factors influencing eating disorders are personality traits. The authors analyse temperament and character of healthy women. METHOD: The Cloninger Temperament and character Inventory was applied to 52 eating disordered patients (33 with anorexia nervosa and 19 with bulimia nervosa). The patients were divided into subgroups of restrictive type and bulimic types of anorexia, bulimia and bulimic episodes. RESULTS: In all the subgroups of the patients a higher result was obtained on the harm avoidance scale (HA), cooperativeness (C) and the self transcendence ST2 subscale. Lower results were seen in self-directedness (SD) in the SD2, SD3 and SD5 subscales. The subgroups differed in temperament. Bulimia patients noted a higher need for NS stimulation and a higher reward dependence (RD). Anorectic patients had higher results in the persistance scale (P), whilst the restrictive anorectic patients had lower results in the NS1 and RD3 subscales. CONCLUSIONS: The TCI Inventory is a useful tool, helping for a precise measurement of the difference in temperament of anorectic and bulimia patients as compared to their healthy peers.

[Some hormones secretion and personality in anorexia nervosa syndrome]. / Wydzielanie niektórych hormonów a osobowosc w jadlowstrecie psychicznym.

The relationship between plasma leptin, some hormones (GH, IRI, IGF-1, DHEA-S, LH, FSH, T, E2, TSH, fT3, fT4), glucose level, personality dispositions and adipose tissue content in 22 women with anorexia nervosa were evaluated. Some personality features as: defensiveness, domination and aggression necessities, high self-control, bad self-estimation, retiring, expectation of custody--correlated with some hormones (LH, E2, IGF-1, fT3, F, T) and leptin level. The ascertained relationships suggest that still unexplained causes generate simultaneous disturbances in the endocrine and psychic processes in central nervous system of anorexia nervosa patients. Probably hormonal and neurotransmitter derangement are the adaptive changes allowing longer survival, as the low leptin secretion in the severest undernutrition states is.

[The endocrine mask of a developing process of schizophrenia--case study]. / Maska endokrynna rozwoju procesu schizofrenicznego--studium przypadku.

In this research psychic and somatic symptoms related to disturbances of hypothalamus-hypophysis-peripheral regulation which may occur in the schizophrenic process were analysed. Authors discussed the problem of relations between hypothalamus neuroregulation and pathogenesis of endocrine disturbances which suggest the organic cause of obesity, hirsutism and secondary amenorrhea among women diagnosed with paranoid schizophrenia. Actual antipsychotic pharmacological treatment, including some side-effects: the metabolic (obesity) and the endocrine (hyperprolactinemia) ones were considered. The authors conclude that endocrine disorders which are connected with hypothalamus disfunction (sleeping, eating and reproductive functions) may reach the psychotic symptoms and treating them influences at the same time some endocrine changes. The estimation of PRL release in a test of stimulation with metoclopramide can be a sensitive (though not specific) test of dopaminergic activity in tuberous--infundibulum pathway and may be used to control the treatment.

Association of eating disorders with catechol-o-methyltransferase gene functional polymorphism.

AIM: The aim of this study was to evaluate functional catechol-O-methyltransferase (COMT) genetic variation as a risk factor for eating disorders (ED). METHOD: Eighty women receiving treatment for serious ED (52 for anorexia nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low-activity allele and the high-activity allele (H) were determined. RESULTS: The H/H genotype was twice as frequent in the ED group as in the control group (52.5% in the ED group and 25% in controls, chi(2) = 15.5, d.f. = 2, p < 0.001, odds ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients (chi(2) = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio = 4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison to 47.8% of patients from the control group (chi(2) = 13.89, p < 0.001, odds ratio = 6.088). In the anorexia group, H allele frequency was enhanced even higher (70.2 vs. 47.8%, chi(2) = 14.48, p < 0.001, odds ratio = 8.175). The genotype associations in the subgroup of bulimia patients were not significant, but a trend for a higher frequency of the H allele was found (p = 0.084, odds ratio = 5.309). CONCLUSIONS: These findings seem to suggest that a turnover of catecholamines, connected with polymorphism determining high activity of COMT enzyme, is connected with the risk of ED occurrence, particularly anorexia nervosa. The risk is significantly higher for women with an allele of higher activity.

[Leptin and it's potential role in the pathomechanism of some hormonal and metabolic disorders of patients with anorexia nervosa]. / Leptyna i jej potencjalny udzial w patomechanizmie niektórych zaburzen hormonalnych i metabolicznych u chorych z jadlowstretem psychicznym.

UNLABELLED: The obese gene product--leptin (LEP)--is a hormone released from adipose tissue implicated in the regulation of nutritional state and energy balance. The aim of this study was to assess the relationship between plasma LEP levels and nutritional state, secretion of hormones of the hypothalamic-pituitary axis, and personality traits in patients with anorexia nervosa (AN). The study was performed in 22 women with AN aged 19.45 +/- 0.92 yrs, mean BMI of 15.48 +/- 0.29 kg/m2, 14 healthy women with normal body weight (NW), aged 29.71 +/- 2.4 yrs, mean BMI of 21.22 +/- 0.43 kg/m2, and 19 obese women without metabolic disorders (OTY), aged 34.5 +/- 2.65 yrs, mean BMI of 37.47 +/- 2.06 kg/m2. Hormone levels were measured with RIA test kits. Psychological examination was carried out by means of Gough-Helibrun's and Catell's personality tests. Body mass index (BMI) and body composition, i.e. body fat mass (BF) and body fat percentage (%BF) were determined with a DEXA instrument (Lunar Co., WI, USA). Absolute plasma LEP levels and the LEP/%BF index were lowest in patients with AN whereas LEP/BF index did not differ among AN, NW, and OTY groups (Table 1). In all groups, LEP levels were positively correlated with BMI, BF, and %BF (Table 2). Plasma neuropeptide Y (NPY), beta-endorphin (B-EP), and galanin (GAL) levels in AN were significantly higher than in NW and OTY groups (Table 3). Plasma GAL levels were positively correlated with LEP/BF and LEP/%BF in AN patients only. Moreover in the AN group, serum/plasma levels of insulin (I), insulin-like growth hormone-1 (IGF-1), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and free triiodothyronine (fT3) were significantly lower, and levels of cortisol (F) significantly higher than in NW and OTY groups (Table 4). Plasma LEP levels in AN patients were positively correlated with IRI, IGF-1, free thyroxine (fT4), and FSH levels, and negatively correlated with thyrotrophin (TSH) levels. Personality traits in patients with AN were significantly correlated with hormone levels (Tables 5 and 6), BMI and body fat content (Table 6). CONCLUSIONS: 1) Leptin secretion from adipose tissue is not related to the nutritional state. 2) High levels of NPY, beta-EP, and GAL in AN confirm that starvation is deliberate in these patients. Low LEP levels in AN may lead to secondary amenorrhea and thyroid function disorders, as well as enhanced cortisol and growth hormone secretion of hypothalamic origin. A positive correlation between levels of LEP and IGF-1 and IRI may reflect mechanisms preserving adipose tissue and protecting from hypoglycemia and insulin resistance. A positive correlation between LEP and fT4 levels suggests a tendency to energy-sparing under conditions of low energy intake. Lack of correlation between LEP and F levels apparently reflects peripheral cortisol resistance in AN. 3) Both undernutrition and abnormal hormone secretion (LEP, F, fT3, IGF-1, LH, E2) are related to social self-withdrawal, defensive attitudes, low self-esteem and high level of self-supervision in AN.