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The 5HT1D Receptor Gene in Bipolar
Disorder: A Family-based Association StudyEmanuela Mundo, M.D., Gwyneth Zai, Lisa Lee, B.Sc., Sagar V. Parikh, M.D.,
and James L. Kennedy, M.D.The serotonin (5HT) receptor genes are considered good
candidates for Major Depression (MD), Bipolar Disorder
(BP), and Obsessive-Compulsive Disorder (OCD). The
5HT1D receptor gene has at least three polymorphisms
known: G861C, T-261G, and the functional T371G (Phe-
124-Cys). The aim of this study was to investigate for the
presence of linkage disequilibrium between the 5HT1D
receptor gene and BP. Two hundred and ninety probands
with DSM-IV BPI, BPII, or Schizoaffective Disorder
(Bipolar type) with their living parents were recruited.
Genotyping data for the G861C and T371G polymorphisms
were analyzed using the Transmission Disequilibrium Test
(TDT). One hundred and sixty triads were informative for
the TDT on the G861C polymorphism, which showed no
preferential transmission of either allele (chi-square 0.438, df 1, p .508). Only four triads were suitable for
the analysis on the T371G variant, with the T allele
transmitted once and the G allele transmitted four times to
the affected. These findings validate further the results of
pharmacological studies excluding a direct involvement of
the 5HT1D receptor in the pathogenesis of BP. Further
investigations combining genetic and pharmacological
strategies are warranted.
[Neuropsychopharmacology 25:608613, 2001]
2001 American College of Neuropsychopharmacology.
Published by Elsevier Science Inc.KEY WORDS: Bipolar disorder; Genetics; Linkage;
Transmission disequilibrium test; 5HT1D receptorBipolar Disorder (BP) is a chronic and serious psychiatric condition that affects approximately one percent of
the general population and it is characterized by recurrent episodes of depression and mania (American Psychiatric Association 1994). Several studies have pointed
out that in the pathogenesis of BP there is a strong genetic component (McGuffin and Katz 1989; Nurnberger
and Gershon 1992). BP patients usually experience abnormalities in mood, sleep, sexual behavior, and appetite, functions that are regulated by the serotonin (5HT)
system (Meltzer 1989). Moreover, compounds acting on
5HT system (i.e, selective serotonin reuptake inhibitors)
have been found to successfully treat bipolar depression (Potter 1998). For these reasons genes of the serotonin system have been considered good candidates for
BP (Peroutka 1995) and, thus, have been investigated in
several studies. To date, results from these studies are
conflicting, but overall seem to exclude the direct involvement of...