Association study of PDE4B with panic disorder in the Japanese population

BackgroundPanic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population.MethodsWe genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared.ResultsWe found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P = 0.031, OR = 1.81, 95% CI = 1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P = 0.042, genotype P = 0.0034; haplotype C-T-T-A, permutation P = 0.028).ConclusionOur results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions.

Research Highlights► The PDE4B gene has been reported to be associated with psychiatric disorders including schizophrenia, bipolar disorder and depression. ► The PDE4B gene, which regulates intracellular cAMP signaling, is suggested to be involved in the pathophysiology of anxiety. ► A significant association was found between PDE4B and PD in female and in all samples. ► Chronic treatment with antidepressants and PDE4B inhibitors reduces the function of PDE4B and increases the level of cAMP and phospholyration of CREB and neurogenesis in the hippocampus, which might produce antidepressant and anxiolytic effects.