Cited by 341Circadian rhythm and melatoninGenetic Associations and EpidemiologyNeurotransmitter Receptor Influence on Behavior

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Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Johansson, Carolina, Willeit, Matthäeus, Smedh, Christina, Ekholm, Jenny, Paunio, Tiina, Kieseppä, Tuula, Lichtermann, Dirk, Praschak-Rieder, Nicole, Neumeister, Alexander, Nilsson, Lars-Göran, Kasper, Siegfried, Peltonen, Leena, Adolfsson, Rolf, Schalling, Martin, Partonen, Timo·2003·Neuropsychopharmacology

DOI 10.1038/sj.npp.1300121

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Abstract

Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness-eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n=177) and diurnal preference (n=92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (chi(2)=9.90, Bonferroni corrected P=0.035), indicating a recessive effect of the leucine allele on disease susceptibility (chi(2)=6.61, Bonferroni corrected P=0.050). Period3 647 Val/Gly was associated with self-reported morningness-eveningness scores (n=92, one-way ANOVA: F=4.99, Bonferroni corrected P=0.044), with higher scores found in individuals with at least one glycine allele (t=3.1, Bonferroni corrected P=0.013). A second, population-based sample of individuals selected for high (n=127) or low (n=98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case-control material (n=177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

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Authors: Johansson, C., Willeit, M., Smedh, C., Ekholm, J., Paunio, T., Kieseppä, T., Lichtermann, D., Praschak-Rieder, N., Neumeister, A., Nilsson, L.-G., Kasper, S., Peltonen, L., Adolfsson, R., Schalling, M., & Partonen, T.
Affiliations: Karolinska Institutet (SE)
Umeå University (SE)
University of Bonn (DE)
University of Vienna (AT)
Stockholm University (SE)
University of California, Los Angeles (US)
Corresponding author: Johansson, Carolina
ORCID: Johansson, Carolina
Ekholm, Jenny
Paunio, Tiina
Kieseppä, Tuula
Praschak-Rieder, Nicole
Nilsson, Lars-Göran
Kasper, Siegfried
Peltonen, Leena
Adolfsson, Rolf
Schalling, Martin
Partonen, Timo
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2002-12-03
Volume: 28
Issue: 4
Pages: 734-739
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300121
OpenAlex: W2145111083
Cited by: 341
References: 36
Citations by year: 2026: 6 · 2025: 1 · 2024: 9 · 2023: 11 · 2022: 3 · 2021: 12 · 2020: 13 · 2019: 4 · 2018: 18 · 2017: 15 · 2016: 17 · 2015: 15 · 2014: 15 · 2013: 18 · 2012: 23
FWCI: 3.34
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
Funders: Karolinska Institutet
Medical Research Council
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: seasonal affective disorder, clock genes, diurnal preference, chronotype, seasonal variation, circadian rhythm disruption, genetic polymorphism, NPAS2, Period2, disease susceptibility
MeSH terms: Analysis of Variance, Circadian Rhythm, Female, Genotype, Humans, Male, Nerve Tissue Proteins, Nuclear Proteins, Polymorphism, Genetic, Proteins, Transcription Factors, Trans-Activators, Chi-Square Distribution, Case-Control Studies, Seasonal Affective Disorder, Statistics, Nonparametric, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, Period Circadian Proteins

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Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

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