In this study, we have investigated the association between clinical variables, levels of oxidative stress markers, and Na+-K+ATPase activity in OCD patients. The main finding of this study was significant differences in the levels of oxidative stress markers between two groups. Also, patients with OCD had lower ATPase activity compared to healthy controls.
Some case control studies (33–40) and a meta-analysis (41) concentrated on the relationship between OCD and MDA. In contrast with our study, Ranjekar et al. observed no significant differences in serum levels of lipid peroxidation markers between patients with schizophrenic and healthy control (42), and kurup et al. found that OCD patients had lower MDA level than controls (43). Also, Ersan et al. (34) and Shohag et al. (35) observed a significant decreased level of vitamin E in serum of OCD patients, but Shohag et al. did not observe any significant difference regarding serum vitamin A levels between OCD and healthy controls. A meta-analysis found an inverse association between vitamin E blood levels and OCD (44). In the present study, serum GSH and TAC levels were not significantly different between two groups. In line with our results, Behl et al. found no significant difference in GSH levels between the OCD patients vs. controls (33). In contrast, Orhan et al. showed a significantly lower GSH levels in OCD group compared to healthy individuals (37). OCD patients have been suggested to be exposed more often to pre-morbid environmental stressors, such as psychological stressors, perinatal events and other traumatic events. These factors are thought to induce inflammation (45) and oxidative stress with potential induction of neurochemical modifications through various neurotransmitter pathways such as glutamate (46, 47).
Recently, it has been speculated that initially oxidative stress could be adaptive via enhanced neurotransmission, but it would exaggerate neurophysiological responses in long term with subsequent disruption of physiological neurotransmission and enhanced permeability of blood-brain barrier. These events would finally promote inflammatory neuronal damage and subsequent neuronal death (47, 48). Thus, oxidative stress might function as a mediator between and disruption of cortico-striato-thalamo-cortical circuit and adverse life events in OCD. Mutually, oxidative stress might be a consequence of environmental exposures due to the OCD over behavior. Indeed, higher prevalence of anxiety disorders, metabolic syndrome, substance use disorders, mood disorders and impulse control disorders have been observed in OCD patients (49, 50). Besides, all of the above mentioned factors have a strong impact on lifestyle and are associated with induction and development of oxidative damage (51–53). There are also some line of evidence supporting the reduced oxidant markers and enhanced antioxidant markers using antidepressants in the setting of OCD and major depression disorder (54, 55).
To the best of our knowledge, only one case-controlled study has investigated Na+-K+ATPase activity in OCD subject (43). In contrast with this study, we found that Na+-K+ATPase activity was significantly lower in OCD patients than in controls. In line with our results, Banerjee et al. (2011) found a significantly diminished activity of Na+-K+ATPase in erythrocytes from patients with bipolar disorder (56). Kirshenbaum et al. (2011) found that a mutation resulting in lower neuronal Na+-K+-ATPase activity would interact with stress exacerbating depression in mice. Furthermore, they observed a significant correlation between mood and Na+-K+ATPase activity that could be related to both bipolar disorder and unipolar depression (57). Na+-K+ATPase also function as a signal transducer besides its principal transport function. The involvement of Na+-K+ATPase-mediated signaling has been reported in various physiological processes such as inflammation, cell growth, differentiation, kidney function, muscle contractility and behavior. OCD can also be considered as a prototypical compulsivity disorder and kind of ‘‘behavioral addiction’’ (58, 59). Numerous investigations have shown elicited behavioral alterations due to mutations in Na+-K+ATPase isoform (21, 60–66). Overall, data support the role of Na+-K+ATPase activity in determining behavior.
This current study had several limitations. Firstly, oxidative markers could be influenced by various factors, such as age, smoking or body mass index (67, 68). We adjusted for several important confounding factors in our analysis, such as smoking and body mass index. Secondly, because the sampling of patients in the present study coincided with the outbreak of coronavirus, this may have an effect on our study, although all subjects had OCD before the onset of the pandemic. Thirdly, patient group interviewed by two independent psychiatrists, but controls group just interviewed by a clinical psychologist, because they may be had another psychiatric disorder (spatially personal disorder). Studies have shown that common tools for investigation of mental health are not accurate (69). These cases seem to lead to the use of more reliable methods such as molecular methods to improve diagnosis (Perhaps it can help diagnose disorders at an early age). Indeed, none of the biomarkers have sufficient sensitivity and specificity as a diagnostic biomarker. Prediction of clinical outcomes seems to be a promising field of research pursuing appropriate biomarkers for OCD (70).
In conclusion, our findings indicate significantly higher levels of MDA in both serum and RBC membrane, lower levels of serum vitamin A and E, and lower activity of membrane Na+-K+ ATPase in OCD patients compared to controls. These findings suggest an imbalance between oxidant and antioxidant factors in OCD patients that might play a fundamental role in etiopathogenesis of OCD.