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. 2014 Oct 31;18(1):pyu034.
doi: 10.1093/ijnp/pyu034.

Familial risk for major depression is associated with lower striatal 5-HT₄ receptor binding

Karine Madsen  1 , Eva Torstensen  1 , Klaus K Holst  1 , Mette E Haahr  1 , Ulla Knorr  1 , Vibe G Frokjaer  1 , Malene Brandt-Larsen  1 , Pernille Iversen  1 , Patrick M Fisher  1 , Gitte M Knudsen  2
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Familial risk for major depression is associated with lower striatal 5-HT₄ receptor binding

Karine Madsen et al. Int J Neuropsychopharmacol. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Int J Neuropsychopharmacol. 2016 Apr 27;19(10):pyw031. doi: 10.1093/ijnp/pyw031. Int J Neuropsychopharmacol. 2016. PMID: 27207904 Free PMC article. No abstract available.

Abstract

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 [(11)C]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.

Keywords: 5-HT4 receptor; MDD; PET; depression; serotonin.

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Figures

Figure 1.
Figure 1.
The distribution of [11C]SB207145 binding potentials in 3 young (24–30 yrs) males scanned at the HRRT scanner. Binding levels are high in the striatum, intermediate in the temporal and limbic areas, and low in the neocortex. (A) The distribution in a subject without a family history of depression. (B) Lower binding potentials in a subject who reported to have one first-degree relative with MDD, and (C) even lower binding potentials in a subject who reported to have 2 first-degree relatives with MDD.
Figure 2.
Figure 2.
The estimated linear association between 5-HT4 receptor binding in the striatum (corrected for age, gender, and scanner type) and the number of first-degree relatives treated for major depression (p = 0.001), with pointwise 95% confidence limits and partial residuals (reference: male, mean age 36 years; GE Advance). A leave-one-out analysis showed that the estimated association was not strongly driven by any single observation in the data (p values in the range 0.0003–0.005).
See this image and copyright information in PMC

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