Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes excluded in generalized social phobia

Social phobia, particularly the generalized form, is strongly familial and frequently comorbid with major depression, panic disorder, and obsessive-compulsive disorder. It has also recently been shown to be responsive to selective serotonin reuptake inhibitors. We conducted a study to determine if generalized social phobia is genetically linked to either of two candidate genes: the serotonin transporter protein (5HTT) gene, or the 5HT2A receptor (5HT2AR) gene. Rates of social phobia (using several phenotype definitions) were ascertained and blood samples obtained from consenting first-degree family members of generalized social phobic probands. 5HT2AR and 5HTT genotyping was performed using the polymerase chain reaction (PCR). Linkage was tested using LINKAGE and GENEHUNTER software. No evidence of linkage was found; power analysis indicated that failure to find linkage was unlikely due to inadequate statistical power. These findings reasonably exclude linkage between generalized social phobia and the 5HTT or 5HT2AR genes in these samples, although modifier effects cannot be ruled out. Other 5HT receptor subtypes or indirect modulatory effects of 5HT on other neurotransmitter systems may be involved.