title: Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels.
abstract: OBJECTIVE
  Previous studies have shown an association between childhood attention deficit hyperactivity disorder (ADHD) and a down-regulated hypothalamus-pituitary-adrenal axis (HPA axis) with low diurnal cortisol levels. Given the role of the FK506 binding protein 5 (FKBP5) as an important regulator of the negative feedback system of the HPA axis, we set out to investigate possible associations between single nucleotide polymorphisms (SNPs) in FKBP5 in relation to ADHD and diurnal cortisol levels.
  
  
  METHODS
  Children with ADHD (n = 81) and healthy comparisons (n = 88) collected saliva four times during a regular school day for radioimmunoassay analysis of cortisol and for genotyping of five SNPs in FKBP5 (rs9296158, rs1360780, rs9470080, rs7748266 and rs9394309).
  
  
  RESULTS
  We found associations between SNP genotypes and ADHD as well as between genotypes and diurnal cortisol levels. One of these SNPs, rs9470080, was significantly associated with both ADHD and lower cortisol levels.
  
  
  CONCLUSIONS
  This study contributes to previous findings on a down-regulated HPA axis in children with ADHD by demonstrating an association between ADHD, lower cortisol levels and SNPs of the FKBP5-gene. The relevance of these findings for the development and shaping of ADHD symptoms needs to be approached in larger samples, preferably also taking stress reactivity into consideration.
authors.affiliation: Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Isaksson
authors.affiliation: Department of Immunology, Genetics and Pathology, Genomics, Uppsala University, Uppsala, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Allen
authors.affiliation: Centre for Clinical Research, Uppsala University, Hospital of Västmanland, Uppsala, Sweden.
authors.forename: Kent W
authors.initials: KW
authors.lastname: Nilsson
authors.affiliation: Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala, Sweden.
authors.forename: Frank
authors.initials: F
authors.lastname: Lindblad
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002940:Circadian Rhythm; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012463:Saliva / Q000737:chemistry; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D006854:Hydrocortisone; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Attention deficit hyperactivity disorder; Cortisol; FK506 binding protein 5; Feedback regulation; Hypothalamus-pituitary-adrenal axis