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.