Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference.
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.
Johansson
Carolina
C
Neurogenetics Unit, Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. carolina.johansson@cmm.ki.se
Willeit
Matthäeus
M
Smedh
Christina
C
Ekholm
Jenny
J
Paunio
Tiina
T
Kieseppä
Tuula
T
Lichtermann
Dirk
D
Praschak-Rieder
Nicole
N
Neumeister
Alexander
A
Nilsson
Lars-Göran
LG
Kasper
Siegfried
S
Peltonen
Leena
L
Adolfsson
Rolf
R
Schalling
Martin
M
Partonen
Timo
T
D000704:Analysis of Variance; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D016574:Seasonal Affective Disorder / Q000235:genetics*; D018709:Statistics, Nonparametric; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C104264:NPAS2 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C538943:CLOCK protein, human