Lack of relationship between CO₂ reactivity and serotonin transporter gene regulatory region polymorphism in panic disorder

Abstract

Changes in the function of the serotonergic system influence both panic phobic symptoms and carbon dioxide (CO2) reactivity in patients with panic disorder. Schmidt et al. [2000: J Abnorm Psychol 109(2):308-320] recently reported a predictive role of the genetic variants of the 5-HTTLPR on the fearful response to CO2 in healthy controls. We tested the hypothesis that the heterogeneity of CO2 reactivity in patients with panic disorder could be related to the allelic variation of the 5-HTT promoter. Ninety-five patients with panic disorder were challenged with 35% CO2. 5-HTTLPR allelic variation in each subject was determined using a PCR-based method. There were no differences for all the measures of CO2 reactivity among the genotype groups. CO2 reactivity of patients with panic disorder seems not to be influenced by the genetic variants of the 5-HTTLPR; this finding does not support a role for the serotonin transporter in the etiopathogenesis of CO2 reactivity in panic disorder.

Serotonin Function in Panic Disorder: Important, But Why?

“…Also Schmidt et al (2000) reported that subjects homozygous for the long variant were at greater risk for behavioral hyper-reactivity to 35% CO 2 challenge than those with short-allele genotypes. On the contrary, in patients with PD, CO 2 reactivity was not influenced by 5-HTTLPR genetic variants (Perna et al, 2004). On the other hand, the long-allele variant of 5-HTTLPR has been associated with a better response to SSRI treatment in females with PD (Perna et al, 2005).…”

Panic comorbidity with bipolar disorder: what is the manic–panic connection?

“…These polymorphisms have been found in two meta‐analyses to have a small but statistically significant association with bipolar disorder (191, 192), and in one study specifically with rapid cycling bipolar disorder (193). Although there are no positive reports in panic disorder, there is evidence that a SERT polymorphism is associated with panic vulnerability to cholecystokinin‐induced (194) but not carbon dioxide‐induced panic attacks (195). The SERT polymorphism has also been associated with increased emotional reactivity and excitation of the amygdala (196–198).…”

Genetic moderation of CO2-induced fear by 5-HTTLPR genotype

“…A study in healthy volunteers showed that the LL genotype (homozygous for the L-allele) predicted a greater fearful response to a single 35% CO 2 inhalation (Schmidt et al, 2000). Although this result could not be replicated in patients with PD (Perna et al, 2004), the same researchers demonstrated that the presence of the L-allelic variant was associated with a better therapeutic response to the serotonin reuptake inhibiting drug paroxetine in PD (Perna et al, 2005).…”