1. Introduction
Obsessive–compulsive disorder (OCD) is a common neuropsychiatric
disorder characterized by obsessions and/or compulsions that cause
significant distress and interfere with normal functioning at work, at
home, in social activities, or in personal relationships. Approximately
80% of OCD cases begin in childhood; the prevalence in children and
adolescents is 0.1–4% [1]. Psychiatric comorbidity is high in
child and adolescent OCD patients, with anxiety, mood, and tic disorders
being the most common comorbidities [2].
The biological mechanisms underlying OCD are not sufficiently elucidated
[3]. Neuroinflammation-mediated changes in the brain caused by
stress and changes in the immune system may contribute to the etiology
of OCD. Recent reports have identified immune system alterations in OCD
patients. Despite strong recent interest in immunologic abnormalities in
OCD, few studies have examined cytokines in this disorder [4].
Cytokines, which increase with chronic inflammation, were shown to
increase neopterin and decrease tetrahydrobiopterin (BH4) levels by
activating the neopterin–BH4 pathway. Neopterin, a biopterin precursor
that is released by macrophages, is accepted as a biochemical marker of
cell-mediated immune responses [5]. In addition, studies have shown
that it can be an important biomarker in psychiatric disorders,
especially major depressive disorder [6]. BH4 is the main cofactor
for the speed-limiting steps in the conversion of phenylalanine to
tyrosine, hydroxylation of tyrosine and tryptophan, and the formation of
serotonin, noradrenaline, and dopamine. Furthermore, BH4 plays an
important role in regulating presynaptic release of neurotransmitters
from nerve terminals [7].
Nitric oxide (NO) levels are associated with increased oxidative stress
cytokines (especially IFN- ɣ), and neopterin elevates NO levels by
increasing reactive oxygen species such as
NADPH-oxidase
(NOX) and superoxide anion
(O2-) and by activating
inducible nitric oxide synthase
(iNOS) [8]. The relationship between inflammation, the neopterin –
tetrahydrobiopterin pathway, and nitric oxide is shown in Fig. 1. NO
participates in the regulation of neurotransmission in the central
nervous system. The importance of monoaminergic systems in the
functioning of the brain is clearly shown by the number of severe
neuropsychiatric diseases caused by impairment of monoaminergic
neurotransmission. NO has been implicated in a number of physiological
functions such as noradrenaline and dopamine release, memory and
learning, and certain pathologies such as schizophrenia, bipolar
disorder, and major depression [9–12].
The cytokines in this research were chosen after literature review and
the selection criteria was mainly based on; the most evaluated cytokines
in adult OCD patients along with the least evaluated cytokines in
pediatric OCD patients.
To our knowledge, this is the first study comparing serum TGF-1β, TNF-α,
IL-1β, IL-2, IL-6, IL-10, IL-17, neopterin, BH4, and NO levels with
child and adolescent patients diagnosed with OCD and a healthy control
group.