Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women

Javier Costas, Mònica Gratacòs, Geòrgia Escaramís, Rocío Martín-Santos, Yolanda de Diego, Enrique Baca-García, Francesca Canellas, Xavier P. Estivill, Roser Guillamat, Miriam Guitart, Alfonso Gutiérrez-Zotes, Luisa García-Esteve, Fermín Mayoral, María Dolores Moltó, Christopher Phillips, Miquel Roca, Ángel Carracedo, Elisabet Vilella, Julio Sanjuán

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Abstract

The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3. days, 8. weeks, and 32. weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapted for post-partum depression. Association with major depression was assessed using likelihood ratio tests under a codominant genotype model. Association with scale scores was tested using linear mixed models to take into account repeated measures over time. Two intronic SNPs, one at the serotonin transporter gene (SLC6A4) and another at dopa decarboxylase (DDC), were significantly associated to STAI anxiety scores after multiple testing correction (nominal P=0.0000513 and 0.000097, respectively). In addition, post hoc analysis at the unphased haplotype level using nominal significant SNPs revealed an association with a combination of three SNPs at protein kinase C, beta (PRKCB) with major depression, significant after multiple testing correction (nominal global P=0.0001596). In conclusion, we detected a role of SLC6A4 in mood changes after stressful events, and revealed new putative associations involving DDC and PRKCB. Therefore, these genes deserve further investigation to confirm these results.

Original languageEnglish
Pages (from-to)717-724
Number of pages8
JournalJournal of Psychiatric Research
Volume44
Issue number11
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

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Keywords

  • Dopa decarboxylase
  • HPA axis
  • Protein kinase C beta
  • Serotonin transporter
  • Sex hormones
  • Tryptophan depletion

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Costas, J., Gratacòs, M., Escaramís, G., Martín-Santos, R., de Diego, Y., Baca-García, E., Canellas, F., Estivill, X. P., Guillamat, R., Guitart, M., Gutiérrez-Zotes, A., García-Esteve, L., Mayoral, F., Dolores Moltó, M., Phillips, C., Roca, M., Carracedo, Á., Vilella, E., & Sanjuán, J. (2010). Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women. Journal of Psychiatric Research, 44(11), 717-724. https://doi.org/10.1016/j.jpsychires.2009.12.012