ISSN 10227954, Russian Journal of Genetics, 2015, Vol. 51, No. 7, pp. 683–694. © Pleiades Publishing, Inc., 2015.
Original Russian Text © A.E. Gareeva, T. Traks, S. Koks, E.K. Khusnutdinova, 2015, published in Genetika, 2015, Vol. 51, No. 7, pp. 799–811.
Schizophrenia is a severe chronic disease charac
terized by disharmony and a loss of unity of mental
functions (thinking, emotions, and motor activity), as
well as significant worsening of social adaptation .
The prevalence of schizophrenia in the world varies
within 0.8–1% and the morbidity rate is 15 individuals
per 100000 population.
Besides the classical means of neurotransmission,
studies of the genetics of the enzymes and receptors
involved in the processes of neuroprotection and neu
rotrophia currently seem to be interesting, since
genetic factors may regulate the balance between neu
rotoxic and neuroprotective responses to stress.
Neurotrophic factors play an important role in the
regulation and development of both the central and
peripheral nervous systems; they are involved in the
processes of survival and the differentiation of neurons
in embryogenesis, as well as synaptic plasticity in dif
ferent regions of the brain . Neurotrophins bind to
specific receptors of the plasmatic membrane: nerve
growth factor (NGF) binds with tyrosine kinase
receptor TrkA (
gene); brainderived neu
rotrophic factor (BDNF) and NT4/5 bind with
tyrosine kinase receptor TrkB (
rotrophin 3 (NT3) binds with tyrosine kinase recep
tor TrkC (
Brainderived neurotrophic factor (BDNF) and
nerve growth factor (NGF) play important role in
neuronal development and neuroprotection. A
decrease in the concentration of BDNF and NGF was
shown in the plasma and serum of patients with
schizophrenia, as well as an increase in their concen
tration in response to treatment with antipsychotic
drugs, which can be a good instrument for the diag
nostics of this disease [3, 4].
According to the literature, patients with schizo
phrenia who have not yet received antipsychotic drugs
 have a lower NGF concentration in liquid and
blood plasma in comparison to the norm. Moreover,
the role of the
gene was shown in the develop
ment of anxiety and irrational fear .
Some investigators showed a decrease in the expres
genes in the prefrontal cortex
of schizophrenia patients [7, 8], which indicates a dis
turbance of the signal transduction of BDNF.
Research of animal knockouts for the
showed disturbed processes of survival and differentia
tion of neocortical neurons . In addition, a decrease
in the level of TrkB protein in serum from schizophrenia
patients was detected , as well as a violation in their
training and behavior in stressful situations . During
an investigation of individuals with suicidal behavior, a
decrease in the expression of tyrosine kinase receptor
TrkB protein in the brain was shown .
gene was shown to influence the func
tion of the hippocampus and to modify the risk of
schizophrenia development . A decrease in
expression in the hippocampus of individ
uals who committed suicide was also reported .
The Role of Neurotrophins and Neurexins Genes in the Risk
of Paranoid Schizophrenia in Russians and Tatars
A. E. Gareeva
, T. Traks
, S. Koks
, and E. K. Khusnutdinova
Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411 Estonia
Department of Pathophysiology, University of Tartu, Tartu, 50411 Estonia
Received June 8, 2014; in final form, December 9, 2014
—Schizophrenia affects about 1% of the population. Its etiology is not fully understood. Environ
mental conditions certainly contribute to the development of schizophrenia, but the determining factor is
genetic predisposition: the coefficient of heritability of schizophrenia is about 80%, which is typical for the
most highly heritable multifactorial diseases. Polymorphic loci of genes of enzymes and receptors involved in
the processes of neuroprotection and neurotrophia play significant role in the development of this disease. In
this paper we investigated 48 polymorphic variants of genes of the neurotrophins and neurexins family
BDNF, NTRK2, NTRK3, NGF, NXPH1
) in Russian and Tatar cases and in a control group liv
ing in the Republic of Bashkortostan. The results of this study confirm the important role of neurotrophin
and neurexin genes in paranoid schizophrenia development.