Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels
Abstract
AIM: 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. CONCLUSION: 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.
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In 81 children with ADHD, wakening levels of cortisol were lower than in controls.
“Isaksson et al. (2015) report that in a case-control study of 81 children with ADHD, wakening levels of cortisol were lower in the ADHD than the control group, and the area under the curve was also lower in the ADHD group for the daily profile compared to controls.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Isaksson et al. (2015)
In 81 children with ADHD, the area under the curve for the daily cortisol profile was lower than in controls.
“Isaksson et al. (2015) report that in a case-control study of 81 children with ADHD, wakening levels of cortisol were lower in the ADHD than the control group, and the area under the curve was also lower in the ADHD group for the daily profile compared to controls.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Isaksson et al. (2015)
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- Authors
- Isaksson, J., Allen, M., Nilsson, K. W., & Lindblad, F.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Isaksson, Johan
- Venue
- Acta Paediatrica
- Publisher
- Wiley
- Published
- 2015-06-26
- Volume
- 104
- Issue
- 9
- Pages
- 910-915
- ISSN
- 0365-1436 (ISSN-L)
- 0803-5253
- OpenAlex
- W1933023939
- Cited by
- 20
- References
- 29
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2018: 2 · 2017: 3 · 2016: 3
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Paediatrica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swedish Brain Foundation, Victoriafonden
- Swedish Council for Working Life and Social Research (2006-0197)
- Uppsala University Hospital Research Fund (ALF)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, FKBP5, single nucleotide polymorphisms, diurnal cortisol, hypothalamic-pituitary-adrenal axis, genetic association, children, stress reactivity
- MeSH terms
- Tacrolimus Binding Protein 5, Attention Deficit Disorder with Hyperactivity, Child, Circadian Rhythm, Female, Genotype, Humans, Hydrocortisone, Male, Saliva, Case-Control Studies, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins
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