ABSTRACT
Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.
Subject(s)
Anorexia Nervosa/genetics , Anorexia Nervosa/psychology , Bulimia Nervosa/genetics , Bulimia Nervosa/psychology , Feeding and Eating Disorders/genetics , Feeding and Eating Disorders/psychology , Tryptophan Hydroxylase/genetics , Adolescent , Adult , Alleles , Body Weight/physiology , Case-Control Studies , DNA/genetics , Data Interpretation, Statistical , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Humans , Male , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Young AdultABSTRACT
INTRODUCTION: The aim of this prospective naturalistic study was to examine for the first time the relationship between dosage, serum concentration and clinical outcome in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. METHODS: Steady state trough serum concentrations of risperidone and 9-hydroxyrisperidone (the active moiety) were measured in 103 subjects. The therapeutic effect was assessed by the clinical global impression improvement subscale and side effects by the Udvalg for Kliniske Undersogelser-side effect rating scale. RESULTS: We found a linear relationship between the risperidone dose and the serum concentration of the active moiety (Spearman rho=0.53) and no correlation between the serum concentration and either the therapeutic effect or side effects. There was no effect of gender and co-medication. DISCUSSION: This study has the typical limitations of naturalistic studies, therefore our results should be interpreted with caution. Based on the serum concentrations at the therapeutically effective dose range (0.25-1.5 mg/day) we obtained first information on a possibly appropriate therapeutic serum range for the risperidone treatment of children and adolescents with impulsive-aggressive symptoms. Further studies with greater sample sizes are needed to validate our results and to examine the influence of genetic polymorphisms on the serum concentration of risperidone.
Subject(s)
Aggression/drug effects , Antipsychotic Agents/therapeutic use , Child Behavior Disorders/drug therapy , Disruptive, Impulse Control, and Conduct Disorders/drug therapy , Risperidone/therapeutic use , Adolescent , Age Factors , Aggression/physiology , Antipsychotic Agents/adverse effects , Antipsychotic Agents/blood , Child , Child Behavior Disorders/blood , Disruptive, Impulse Control, and Conduct Disorders/blood , Dose-Response Relationship, Drug , Female , Humans , Isoxazoles/blood , Linear Models , Male , Paliperidone Palmitate , Prospective Studies , Psychiatric Status Rating Scales , Pyrimidines/blood , Risperidone/adverse effects , Risperidone/blood , Sex Factors , Treatment OutcomeABSTRACT
A 14-year-old girl with suicidal ideation was presented to the paediatric hospital about 2 h after ingestion of 21 long-acting methylphenidate (MPH) 54-mg tablets (1,134 mg Concerta(®)). At admission signs of sympathomimetic syndrome were observed like agitation, visual hallucinations, slight hypertension, and sinus tachycardia. Treatment included prevention of absorption (30 g activated charcoal orally) and careful observation related to the overstimulation of the sympathic system. Despite the intake of charcoal, the serum concentrations of MPH were 107 and 93 ng/ml 2.5 and 22 h after ingestion of MPH tablets. No support of vital functions was necessary. The girl made a full recovery and was discharged after 3 days of care at the paediatric clinic and referred to the child and adolescent psychiatric department. Exposure to a huge overdose of long-acting MPH exhibited acute sympathomimetic toxicity but no life-threatening symptoms in this patient. Thus this case report suggests that patients intoxicated with high dose long-acting MPH formulations can recover without sequelae when managed properly.
Subject(s)
Central Nervous System Stimulants/poisoning , Delayed-Action Preparations/poisoning , Methylphenidate/poisoning , Suicidal Ideation , Adolescent , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/blood , Delayed-Action Preparations/pharmacokinetics , Drug Overdose , Female , Humans , Methylphenidate/administration & dosage , Methylphenidate/bloodABSTRACT
Pharmacological and challenge study data showed an involvement of the serotonergic system in the development of obsessive-compulsive disorder (OCD). We studied transmission disequilibrium of polymorphisms in three candidate genes of the serotonergic pathway in 64 trios comprising patients with early onset OCD and both of their parents. Polymorphisms of the following genes were studied: tryptophan hydroxylase 1 (rs1800532), serotonin transporter (polymorphism in the promoter region; 5-HTTLPR) and the serotonin 1 B receptor (rs6296). This is, to our knowledge, one of the first family based association studies pertaining to children and adolescents with OCD. We did not detect transmission disequilibrium of the investigated polymorphisms in OCD. Hence, these polymorphisms do not play a major role in the genetic predisposition to early onset OCD.
