PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder

J Affect Disord. 2017 Jan 1;207:136-140. doi: 10.1016/j.jad.2016.09.034. Epub 2016 Sep 28.

Abstract

Background: Dysfunctions in the intrinsic clocks are suggested in patients with depressive disorders. The cryptochrome circadian clocks 1 and 2 (CRY1 and CRY2) proteins modulate circadian rhythms in a cell and influence emotional reactions and mood in an individual. The protein kinase C delta binding protein (PRKCDBP, or CAVIN3), similar to the serum deprivation response protein (SDPR, or CAVIN2), reduces metabolic stability of the PER2-CRY2 transcription factor complex that plays a role in the circadian rhythm synchronization. Our aim was to study SDPR, PRKCDBP, CRY1 and CRY2 genetic variants in depressive disorders.

Methods: The sample included 5910 Finnish individuals assessed with the Munich-Composite International Diagnostic Interview (M-CIDI) in year 2000. In year 2011, 3424 individuals were assessed again. After genotype quality control, there were 383 subjects with major depressive disorder, 166 with dysthymia, and 479 with depressive disorders (major depressive disorder, dysthymia or both), and 4154 healthy controls. A total of 48 single-nucleotide polymorphisms from SDPR, PRKCDBP, CRY1 and CRY2 genes were analyzed using logistic regression models controlling for age and gender.

Results: The earlier reported association of CRY2 variants with dysthymia was confirmed and extended to major depressive disorder (q<0.05). In addition, novel associations of PRKCDBP rs1488864 with depressive disorders (q=0.02) and with major depressive disorder in specific (q=0.007) were found.

Limitations: The number of cases was moderate and coverage of PRKCDB was limited.

Conclusions: CRY2 and PRKCDBP variants may be risk factors of major depressive disorder and provide information for diagnosis.

Keywords: Diurnal; Genetic association; Health examination; Population.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carrier Proteins / genetics
  • Circadian Rhythm / genetics
  • Cryptochromes / genetics*
  • Depressive Disorder, Major / genetics*
  • Dysthymic Disorder / genetics*
  • Female
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Phosphate-Binding Proteins
  • Polymorphism, Single Nucleotide

Substances

  • CAVIN2 protein, human
  • CAVIN3 protein, human
  • CRY1 protein, human
  • CRY2 protein, human
  • Carrier Proteins
  • Cryptochromes
  • Intracellular Signaling Peptides and Proteins
  • Phosphate-Binding Proteins