Familial Risk for Major Depression is Associated with Lower Striatal 5-HT4 Receptor Binding

摘要

Background: The 5-HT₄ receptor provides a novel potential target for antidepressant treatment. No studies exist to elucidate the 5-HT₄ receptor’s in vivo distribution in the depressed state or in populations that may display trait markers for major depression disorder (MDD). The aim of this study was to determine whether familial risk for MDD is associated with cerebral 5-HT₄ receptor binding as measured with [11C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD. Methods: We studied 57 healthy individuals (mean age 36 yrs, range 20–86; 21 women), 26 of which had first-degree relatives treated for MDD. Results: We found that having a family history of MDD was associated with lower striatal 5-HT₄ receptor binding ( p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a “risk-dose effect” on 5-HT₄ receptor binding, since the number of first-degree relatives with a history of MDD binding correlated negatively with 5-HT₄ receptor binding in both the striatum ( p = 0.001) and limbic regions ( p = 0.012). Conclusions: Our data suggest that the 5-HT₄ receptor is involved in the neurobiological mechanism underlying familial risk for depression, and that lower striatal 5-HT₄ receptor binding is associated with increased risk for developing MDD. The finding is intriguing considering that the 5-HT₄ receptor has been suggested to be an effective target for antidepressant treatment.