ISSN 1022-7954, Russian Journal of Genetics, 2009, Vol. 45, No. 12, pp. 1475–1479. © Pleiades Publishing, Inc., 2009.
Original Russian Text © R.V. Eﬁmov, A.S. Mavlyudova, V.E. Golimbet, 2009, published in Genetika, 2009, Vol. 45, No. 12, pp. 1668–1673.
Endogenous psychoses represent a group of most
widely distributed mental diseases, schizoaffective dis-
orders, and manic-depressive psychoses (MDP), or
bipolar affective disorders, according to the interna-
tional classiﬁcation of diseases. According to some
estimates, these diseases affect from 0.3 to 1.5% of the
world population .
The role of genetic factors in the development of
endogenous psychoses is conﬁrmed by numerous
investigations. Most authors share the opinion on the
polygenic nature of psychotic disorders. At present, the
search for candidate genes in endogenous psychoses is
in progress [2–6]. There are no doubts that the develop-
ment of these diseases can be caused by disturbances of
brain neurochemical systems. One of the main
approaches towards identiﬁcation of genetic factors
participating in the disease development is analysis of
polymorphism of the genes involved into the main
stages of the disease pathogenesis. The most important
candidate genes for these diseases are those related to
monoaminergic systems of the brain, including dopam-
inergic, noradrenergic, serotonergic, and glutamatergic
systems. At present, using methods of genetic analysis,
an association with different mental disturbances was
reported for not more than 30 genes [6–9].
Serotonergic system is involved in various physio-
logical processes, like appetite, sleep, memory, repro-
duction, and some others. Decrease of serotonin turn-
over, determined as the reduced concentration of
5-hydroxyindoleacetic acid in cerebrospinal ﬂuid, dem-
onstrated association with mood disturbances, like sui-
cidal and impulsive behavior, depressions, and early
alcoholism [10, 11]. Linkage studies revealed a number
of polymorphisms associated with psychotic disorders
and located in the genes affecting metabolism and func-
tioning of serotonergic system. These are the genes for
serotonin receptors 5-HT1A, 5-HT2A, and 5-HT1C,
serotonin transporter, monoamine oxidases A and B,
and tryptophan hydroxylase. Association of the poly-
morphic markers of these genes with mood disorders is
actively studied [12–17].
Tryptophan hydroxylase (TpH) is the key enzyme of
serotonin biosynthesis. Serotonin is synthesized from
tryptophan amino acid. Tryptophan hydroxylase cata-
lyzes transformation of tryptophan into 5-hydroxytryp-
tophan, which I decarboxylated to form serotonin.
Tryptophan hydroxylation is the slowest reaction in the
serotonin pathway, which determines the total rate of
serotonin biosynthesis .
At present, full sequence of the gene coding for the
tryptophan hydroxylase has been determined [19, 20].
The gene spans a region of 29 kb and contains 11 exons
along with single promoter and transcription initiation
site. The TpH gene polymorphisms have been the sub-
jects of intensive study regarding their possible associ-
ation with behavioral dysfunctions [21, 22]. These
studies tested the samples from different populations,
including Russian . In a number of molecular
genetic studies, an association between the TpH single
Association between the Tryptophan Hydroxylase (TpH) Gene
Polymorphic Markers and Endogenous Psychoses
R. V. Efimov
, A. S. Mavlyudova
, and V. E. Golimbet
Center for Advanced Medical Technologies, Moscow, 107014 Russia;
Saratov State University, Department of Animal Ecology and Morphology, Saratov, 410012 Russia
Sechenov Moscow Medical Academy, Moscow 119991 Russia
Research Center for Mental Health, Russian Academy of Medical Sciences, Moscow, 115552 Russia
Received February 19, 2009
—Tryptophan hydroxylase is one of the key enzymes involved in serotonergic metabolism. In many
studies, an association between the TpH gene and human mentality, as well as mental disorders was demon-
strated. This study was designed to analyze the association between three TpH gene polymorphisms (A218C,
T3792A, and (CT)
) and endogenous psychoses. The patients included into investigation were rep-
resented by those with manic-depressive psychosis (93 individuals) and those with the schizophrenia spectrum
disorders (307 individuals). An association between the A218C polymorphism with the disorders of the schizo-
phrenia spectrum was demonstrated. These ﬁndings conﬁrmed the data obtained earlier for other populations.
In addition, an association between the (CT)
microsatellite repeats and bipolar disease was shown
for the ﬁrst time.