CRY2 is associated with depression.
BACKGROUND
Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated.


RESULTS
We observed a marked diurnal variation in human CRY2 mRNA levels from peripheral blood mononuclear cells and a significant up-regulation (P = 0.020) following one-night total sleep deprivation, a known antidepressant. In depressed bipolar patients, levels of CRY2 mRNA were decreased (P = 0.029) and a complete lack of increase was observed following sleep deprivation. To investigate a possible genetic contribution, we undertook SNP genotyping of the CRY2 gene in two independent population-based samples from Sweden (118 cases and 1011 controls) and Finland (86 cases and 1096 controls). The CRY2 gene was significantly associated with winter depression in both samples (haplotype analysis in Swedish and Finnish samples: OR = 1.8, P = 0.0059 and OR = 1.8, P = 0.00044, respectively).


CONCLUSIONS
We propose that a CRY2 locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of CRY2 expression.
Lavebratt
Catharina
C
Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden. catharina.lavebratt@ki.se
Sjöholm
Louise K
LK
Soronen
Pia
P
Paunio
Tiina
T
Vawter
Marquis P
MP
Bunney
William E
WE
Adolfsson
Rolf
R
Forsell
Yvonne
Y
Wu
Joseph C
JC
Kelsoe
John R
JR
Partonen
Timo
T
Schalling
Martin
M
D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm; D056931:Cryptochromes / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics* / Q000523:psychology; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012892:Sleep Deprivation / Q000503:physiopathology; D055815:Young Adult
C538966:CRY2 protein, human; D056931:Cryptochromes