Does serotonin 2A receptor gene polymorphism increase the vulnerability to panic attacks?

Many studies have been conducted to show the genetic associations between the serotonin 2A receptor (HTR2A) gene polymorphisms and panic disorder (PD), but the overall results are inconsistent and replication proved difficult. Here, we provide a concise overview of recent findings on genetic association studies with PD, which are summarized in a table. It has been shown that the HTR2A receptor gene 102T-C polymorphism is associated with a pure phenotype, and with agoraphobia in PD patients, and with panic-flight behaviour in healthy volunteers. Furthermore, the polymorphism is quantitatively correlated with panic symptoms severity. Interestingly, a role for this HTR2A 102T-C polymorphism was not found in less well-delineated samples of PD patients, also suffering from co-morbid conditions, nor in PD patients without agoraphobic symptoms. However, the majority of the studies had low sample sizes, and therefore there is a need for a well-designed study with a sufficient statistical power. The genetic association of HTR2A 102T-C polymorphism with PD (related to agoraphobia or panic symptom severity) provides entry points for new studies on molecular mechanisms in PD.