Role of serotonergic polymorphisms in the clinical severity of the panic disorder

To investigate the association between three serotonergic polymorphisms (A-1438G [rs6311] of the HTR2A gene, STin2 VNTR and 5-HTTLPR of the SLC6A4 gene) and the severity of panic and depression symptomatology among mental health outpatients with diagnosis of panic disorder (PD). 92 unrelated PD outpatients (DSM-IV criteria) from a homogeneous Spanish Caucasian population (mean age±SD, 35.9±12.4 years; 28 [30.4%] males) were assessed using the Panic and Agoraphobia Scale (PAS), and the Hamilton Depression Rating Scale (HDRS), and genotyped using standard methods. Age of onset of PD varied by STin2 VNTR genotype (F=3.21; p=0.045). On average, onset of PD occurred earlier for those with the 10/10 than for those with the 12/12 genotype (25.1 νs 33.3; p=0.043). No relationship was found between A-1438G, 5-HTTLPR, and STin2 VNTR genotypes and PAS or HDRS total scores. Variation in scores on the HDRS Anxiety subscale by A-1438G genotype almost reached statistical significance (F=3.03; p=0.053). Post hoc pairwise comparisons showed higher anxiety levels among A/G than among A/A carriers (4.1 νs 2.9; p=0.043). Finally, variation in scores on the Preoccupied with Health subscale of the PAS by 5-HTTLPR genotype approached statistical significance (F=2.56; p=0.083). Post hoc pairwise comparisons showed higher scores among L/S than among L/L carriers (2.4 νs 1.4; p=0.078). Our data provide support of an involvement of the serotonin system, particularly, the HTR2A gene in the severity of PD.