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

Objectives: 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).

Methods: 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.

Results: 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).

Conclusions: Our data provide support of an involvement of the serotonin system, particularly, the HTR2A gene in the severity of PD.