Interaction between serotonin transporter promoter and dopamine receptor D4 polymorphisms on decision making

Appropriate decision making is an important brain function to maintain our lives. The Iowa gambling task (IGT) is a tool for decision making under ambiguity. The aims of this study were to evaluate the influence of serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) polymorphisms and their interaction on IGT performance. One hundred fifty-nine normal subjects were involved in this study. All subjects performed the IGT and were genotyped for the triallelic 5-HTTLPR and DRD4 48 bp uVNTR polymorphisms.After controlling for gender, age, and impulsiveness, there were no main effects of 5-HTTLPR and DRD4 gene polymorphisms on total IGT score. However, there was a significant effect on the interaction between 5-HTTLPR and DRD4 on total IGT score. In the presence of the 5-HTTLPR S′S′ (SS + SL_G + L_GL_G), subjects with the DRD4 2R+ (2 repeat carrier) had higher total IGT score compared to those with the DRD4 2R–. In contrast, in the absence of the 5-HTTLPR S′S′, subjects with the DRD4 2R– had higher total IGT score than those with the DRD4 2R+. When we divided IGT scores into the first and second half of trials, the 5-HTTLPR × DRD4 interaction effects were stronger in the second half block (decision under risk) than in the first half block (decision under ambiguity). In conclusion, the DRD4 genotypes might influence decision-making performance differently according to the background genotypes of 5-HTTLPR.     

Hypnotizability in patients with anorexia nervosa and bulimia

Hypnotizability was assessed with the use of three standardized hypnosis scales in 86 patients with eating disorders. All diagnoses were made according to DSM-III criteria. Sixty-five patients had anorexia nervosa and 21 had bulimia. The anorectic patients were divided into subgroups of 19 abstainers and 46 vomiters and purgers. Bulimic patients were highly hypnotizable, significantly more so than the patients with anorexia nervosa and age-matched populations. There was also a trend for the purging subgroup of anorectics to have higher hypnotic capacity than abstaining anorectics.     

Impulsivity and long-term prognosis of psychiatric patients with anorexia nervosa/bulimia nervosa

Few if any reliable indicators of long-term outcome have been found in eating disorders. Impulsivity was the strongest predictor in the present study of 35 adults with anorexia nervosa or bulimia nervosa. This variable accounted for 25% of anorectic symptoms at 2 to 3 years follow-up and 14% at 4 to 6 years (Eating Attitudes Test). The relationship was specific insofar as impulsivity predicted neither depression nor overall mental health. Cognitive impairment may be one reason for the poor prognosis of impulsive patients.     

Beta 2-adrenergic receptor regulation in circulating mononuclear leukocytes in anorexia nervosa and bulimia

Mononuclear leukocyte (MNL) beta 2-adrenergic receptors and their coupled adenylate cyclase system were studied in underweight anorectics (n = 12), weight-recovered anorectics (n = 8), bulimics (n = 8), and age- and sex-matched controls (n = 39). Compared with controls, underweight anorectics had significantly fewer MNL beta 2-adrenergic receptor sites (Bmax) but did not differ in binding affinity (Kd). Weight-recovered anorectics and bulimics did not differ from controls on either Bmax or Kd. Compared with controls, all three patient groups had significantly reduced plasma levels of triiodothyronine (T3), while only underweight anorectics had significantly elevated plasma levels of cortisol. Plasma norepinephrine (NE) response to orthostasis was significantly lower in the three patient groups than in controls. The reduction in beta 2-adrenergic receptor number in underweight anorectics could reflect their elevated cortisol and reduced T3 levels. The decrease in beta 2-adrenergic receptor sites, together with the lower NE response to orthostasis, could be responsible for the reduced sympathetic activity of underweight anorectics.     

Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds

Early onset of alcohol and tobacco use during adolescence increases the risk for establishing a substance use disorder in adulthood. Both alcohol and nicotine stimulate the dopamine (DA) and the serotonin (5-HT) systems. The DA system has been implicated in the mediation of the rewarding effects of self-administered drugs of abuse. A possible role of an interaction between these neurotransmitter systems in substance use behavior has been suggested but is as yet unknown. The present study was designed to examine the influence of the DA D4 receptor (DRD4) and the serotonin transporter (5-HTT) genotype and their interaction on adolescent alcohol and tobacco experimentation. Participants were from a longitudinal study of a birth cohort consisting initially of 384 children from a high-risk community sample. At the age of 15 years, adolescents completed a self-report questionnaire measuring tobacco and alcohol consumption. DNA was taken from 305 participants (146 boys, 159 girls) and genotyped for the DRD4 exon III and the 5-HTTLPR polymorphisms. The DRD4 7-repeat allele was associated with greater smoking and drinking involvement in boys. In girls, a significant DRD4 × 5-HTT interaction was detected. Girls without the DRD4 7-repeat allele and who were homozygous for the long allele of 5-HTTLPR displayed the highest smoking and drinking activity. The genetic and potential molecular background underlying adolescent vulnerability to substance abuse is discussed.     

Insulin sensitivity in patients with anorexia nervosa and bulimia

Insulin sensitivity was studied using the euglycemic insulin clamp technique in 5 female patients with anorexia nervosa and 4 females with bulimia. The results were compared with those of 15 male patients with non-insulin-dependent diabetes mellitus. Euglycemic insulin clamp is performed for 2 h using the Biostator, during which time insulin was infused at a rate of 0.77 mU kg-1 min-1. Fasting plasma glucose and immunoreactive insulin tended to be lower in patients with anorexia nervosa than in those with bulimia (69.8 +/- 6.7 vs 75.9 +/- 7.7 mg/dl, and 5.9 +/- 2.0 vs 9.8 +/- 3.4 U/ml). The mean metabolic clearance rate (MCR) was 9.2 +/- 3.9 ml kg-1 min-1 for patients with anorexia nervosa, 5.1 +/- 2.2 ml kg-1 min-1 for patients with bulimia, and 3.8 +/- 0.3 ml kg-1 min-1 for patients with diabetes mellitus. However, one anorectic had a significantly high MCR. One anorectic and 3 bulimics had a significantly low MCR. These results suggest that insulin sensitivity varied in patients with anorexia nervosa, whereas it tended to decrease in some patients with bulimia but not to the same degree as in patients with diabetes mellitus.     

Peripheral serotonin transporter DNA methylation is linked to increased salience network connectivity in females with anorexia nervosa

BackgroundEpigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa.MethodsWe obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls. We decomposed imaging data using independent component analysis. We used bisulfite pyrosequencing to analyze blood DNA methylation within the promoter region of SLC6A4. We then explored salience network rsFC patterns in the group × methylation interaction.ResultsWe identified a positive relationship between SLC6A4 methylation levels and rsFC between the dorsolateral prefrontal cortex and the salience network in patients with anorexia nervosa compared to healthy controls. Increased rsFC in the salience network mediated the link between SLC6A4 methylation and eating disorder symptoms in patients with anorexia nervosa. We confirmed findings of rsFC alterations for CpG-specific methylation at a locus with evidence of methylation correspondence between brain and blood tissue.Limitations: This study was cross-sectional in nature, the sample size was modest for the method and methylation levels were measured peripherally, so findings cannot be fully generalized to brain tissue.ConclusionThis study sheds light on the neurobiological process of how epigenetic variation in the SLC6A4 gene may relate to rsFC in the salience network that is linked to psychopathology in anorexia nervosa.     

The validity of the distinction between bulimia with and without anorexia nervosa

The purpose of this study was to examine the relationship between bulimia in women with anorexia nervosa and bulimia of a similar severity in normal-weight women and to determine the support for the distinction between these two groups according to DSM-III criteria. Results indicated that bulimic women with anorexia nervosa (N = 59) and bulimic normal-weight women (N = 59) resembled each other on most variables and were more similar to each other than to women with anorexia nervosa who rigidly restricted food intake (N = 59). The results failed to support the diagnostic distinction between bulimia in anorexic women and bulimia of equal severity in normal-weight women.     

Cerebral atrophy and vigilance performance in patients with anorexia nervosa and bulimia nervosa

The relationship between ventricular size, as a measure of brain atrophy, and performance on a vigilance task was investigated in 39 patients with anorexia or bulimia nervosa during the acute stage of their illness. Compared to normal controls, the patients performed significantly more poorly in the cognitive task. Half of the patients displayed enlarged ventricles. However, the patients with ventricular dilatation did not perform worse in the cognitive test than patients with normally sized ventricles. Other clinical characteristics, such as symptom severity or duration of illness, were also not correlated with ventricular size. These results support the interpretation that cerebral atrophy per se does not have severe consequences on the neuropsychological or psychopathological status in eating disorder patients.     

Adaptation of psychodrama in psychotherapy of patients with anorexia nervosa and bulimia nervosa

The aim of the article was an attempt to present selected theoretical motifs and moreover self experience in the adaptation of elements of psychodrama by Moreno in psychodynamic psychotherapy (individual and group psychotherapy) in a group of people with anorexia and bulimia nervosa. Psychodrama through own creativity, spontaneity and taking action on the "here and now" stage helps to attain and intensify therapeutic aims which concern the consciousness of inner conflict of persons with anorexia and bulimia nervosa, which is translocated on their body.     

Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride.

BACKGROUND: Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). METHODS: To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding. RESULTS: The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. CONCLUSIONS: These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.     

Ego functioning predicts first-year status in adults with anorexia nervosa and bulimia nervosa

Severe personality disturbance is a feature that possibly explains chronicity in eating disorders, a largely inexplicable development in terms of previously investigated factors. We tested this hypothesis in a group of 41 anorectics and bulimics with ratings of 13 ego functions and of status at 1-year follow-up. Patients who still were preoccupied with weight or shape and had a DSM-III-R eating disorder at follow-up had more severe ego disturbance at initial presentation than those who were free from symptoms. The relevance of demographics, syndromal diagnosis and clinical factors other than ego functioning was limited. The importance of ego functioning for prognosis in eating disorders thus appears to overshadow that of several factors that have been extensively cited in the literature.     

Correlates of sexual abuse in women with anorexia nervosa and bulimia nervosa.

Of 184 female outpatients meeting the DSM-III-R criteria, for anorexia nervosa, bulimia nervosa, or anorexia nervosa with bulimia, approximately 25% reported previous sexual abuse. Furthermore, previous sexual abuse was associated with greater psychological disturbance, measured by the Eating Disorder Inventory and Eating Attitudes Test. Sexual functioning did not differ among women who did or did not report sexual abuse. This finding suggests that sexual abuse or its correlates may affect severity rather than type of eating disorder.     

Neuropsychological assessments before and after treatment in patients with anorexia nervosa and bulimia nervosa

In psychiatric patients the identification of cognitive deficits which predict a poor clinical outcome is important for the development of specific treatment strategies aimed at the amelioration of these impaired cognitive functions to increase the likelihood of full clinical remission. However, such attempts are absent in bulimia nervosa (BU), are scarce in anorexia nervosa (AN) and, furthermore, provide conflicting results. In the present prospective study we investigated the neuropsychological demands in 12 patients with AN and in 14 patients with BU before, during, and after a treatment period. At the initial testing session, both patients samples showed similar and impaired performance levels on tasks measuring attentional demands and problem solving abilities, while their mnemonic functions were preserved. At the final testing session, which took place 7 months thereafter, the impaired cognitive functions had improved to a similar degree in the AN and the BU subgroups. However, although the eating disorder symptomatology had ameliorated in parallel, no direct associations could be established with the initial neuropsychological demands and their rectification, respectively. On an individual level, 11 patients initially showed obvious cognitive deficits. However, the clinical characteristics of this subgroup differed not from that found in the 15 'good performers'. These findings indicate that the cognitive functions in the acute AN and BU are similarly impaired, but also ameliorate in a similar manner with clinical remission. Because no associations were obvious between cognitive and clinical rectifications, significant contributions of mediating factors (e.g., changes in metabolic brain turnover and in steroid hormones) are suggested.     

Interaction between LSD and dopamine D2/3 binding sites in pig brain

The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD.     

Altered serotonin 2A receptor activity in women who have recovered from bulimia nervosa.

OBJECTIVE: The authors' goal was to confirm that brain serotonin (5-HT) alterations are present in patients who have recovered from bulimia nervosa. Positron emission tomography imaging with [(18)F]altanserin was used to characterize binding of the 5-HT(2A) receptor, which might contribute to altered feeding, mood, or impulse control. METHOD: Nine women who had recovered from bulimia nervosa (they had no episodes of binge eating or purging, were at normal weight, and had regular menstrual cycles for more than 1 year) were compared with 12 female volunteers who had never had bulimia. RESULTS: The healthy volunteers, but not the women who had recovered from bulimia nervosa, had an age-related decline in 5-HT(2A) binding. Women who had recovered from bulimia nervosa had a reduction of medial orbital frontal cortex 5-HT(2A) binding. CONCLUSIONS: The lack of age-related changes in 5-HT activity is further evidence of 5-HT alterations in subjects who have recovered from bulimia nervosa. In addition, vulnerabilities for eating disorders, impulse dyscontrol, and mood disturbances may involve 5-HT and frontal lobe activity.     

Grey matter volume in adolescents with anorexia nervosa and associated eating disorder symptoms

Anorexia nervosa (AN) is a mental health disorder of complex aetiology. Previous neuroimaging studies have found consistent global reductions in global grey matter volume of underweight girls with AN; however, differences in regional grey matter volumes are less consistent. The aims of this study were to investigate grey matter regional volumes of adolescent girls with AN before and after weight recovery and the relationship of any changes with clinical characteristics. We collected high‐resolution T1‐weighted images from 26 underweight girls with AN before weight gain and 20 healthy control volunteers. Clinical features were assessed using the Eating Disorder Examination Questionnaire. AN subjects displayed reduced grey matter volumes in the insula, amygdala, prefrontal, hippocampal and cingulate cortices and the precuneus, relative to healthy controls. In a subset of 10 AN subjects who were followed after weight recovery, grey matter volumes increased to near‐control levels in the orbito‐ and medial prefrontal, insular, left hippocampal and mid‐ and posterior cingulate cortices and precuneus. The recovery of the right anterior thalamus and the left orbitofrontal cortex was correlated with improvements in eating concerns and shape concerns, respectively. However, large parts of the anterior cingulate cortex, caudate nuclei and right hippocampus did not display any grey matter recovery following a short‐term of treatment. These results show that in adolescents with AN, some brain regions display marked recovery in grey matter volume following weight recovery, whereas others do not, considering grey mater recovery possibly linked to symptom improvement.     

Perception of family functioning and depressive symptomatology in individuals with anorexia nervosa or bulimia nervosa

This study investigated the relationship between the perception of family functioning and depressive symptomatology in individuals with eating disorders (EDs). Subjects were evaluated by diagnostic clinical interview using DSM-III-R criteria for EDs, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), and two self-report measures, the Beck Depression Inventory (BDI) and the Family Assessment Device (FAD). A significant association was found between self-reported depressive symptomatology and perceived poor family functioning. Subjects with bulimia nervosa (BN) reported a significantly more dysfunctional family background than subjects with anorexia nervosa (AN). In our sample, the presence of self-reported depressive symptomatology was a more powerful predictive variable for perceived family dysfunction than the diagnosis of affective disorder. Also, the diagnosis of BN was a more consistent predictor of dysfunctional family interaction than the diagnosis of affective disorder. Depressive symptoms and EDs seem to play different roles in the way in which they contribute to dysfunctional family patterns.