A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder
Abstract
Age at onset of bipolar disorder might represent the penetrance of the system for specific genetic liability involved in the genesis of the illness. Genetic factors influencing age at onset have been shown to play a role in shaping core characteristics of the illness, such as severity and pattern of recurrence. Genetic variants of genes regulating the circadian clock could contribute to define endophenotypes of bipolar disorder, and have been associated with clinical features of the disease. The coding region of Per3 gene contains a variable-number tandem-repeat (VNTR) polymorphism which has been associated with diurnal preference, sleep structure and sleep homeostasis in healthy subjects. In a homogeneous sample of 99 patients affected by bipolar disorder type I we observed that Per3 VNTR influenced age at onset of illness: earlier age at onset in homozygote carriers of Per35 variant, later in homozygotes for Per34, and intermediate in heterozygotes. Allele frequencies were not significantly different from those reported in healthy subjects. Results need to be confirmed in larger samples, but warrant interest for the variants of molecular clock genes as possible endophenotypes of bipolar disorder.
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Polymorphisms of clock genes such as CLOCK, Per3, and GSK3-β can influence both the individual activity-rest rhythm and core characteristics of bipolar illness such as age at onset, recurrence of illness episodes, insomnia, and response to mood stabilizers.
“Polymorphisms of clock genes such as CLOCK, Per3, and GSK3-β, can influence both the individual activity-rest rhythm and core characteristics of bipolar illness such as age at onset, recurrence of illness episodes, insomnia, and response to mood stabilizers (Benedetti et al., 2008; Benedetti et al., 2003).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Benedetti et al., 2008
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- Authors
- Benedetti, F., Dallaspezia, S., Colombo, C., Pirovano, A., Marino, E., & Smeraldi, E.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Benedetti, Francesco
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 445
- Issue
- 2
- Pages
- 184-187
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2085129479
- Cited by
- 149
- References
- 42
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 4 · 2018: 8 · 2017: 12 · 2016: 12 · 2015: 10 · 2014: 17 · 2013: 9 · 2012: 12
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- Per3, bipolar disorder, age of onset, clock genes, variable number tandem repeats, VNTR polymorphism, genetic susceptibility, endophenotypes, diurnal preference, sleep homeostasis
- MeSH terms
- Adolescent, Adult, Aged, Analysis of Variance, Bipolar Disorder, Female, Gene Frequency, Genotype, Humans, Italy, Male, Middle Aged, Nuclear Proteins, Polymorphism, Genetic, Transcription Factors, Chi-Square Distribution, Age of Onset, Minisatellite Repeats, Young Adult, Period Circadian Proteins
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