Central nervous system and immune system are systems which are in interaction with each other [7]. Immune cells and molecules play a crucial role in forming the brain functions by affecting the cognitive and emotional processes [8].
In this study, the range for age of patients was 3 -15 years with the mean 8 years in ADHD group this supported by CDC, 2016 that reported the average age of ADHD is 7 years. The mean age in ASD was 5.5 years, this was supported by American Academy of Pediatrics, 2017 that reported that the average age of diagnosis is about 4.5 years [9, 10].
Males represented 76% in ADHD group while females represented 24%, this is in line with Danielson et al. 2018 who reported that boys being over-represented, on average, approximately 2:1 [7].
Males represented 52% of the ASD group while females represented 48% in ASD group, this supported by current estimates of CDC, 2018 that ASD is more than 4 times among boys than among girls [11].
In this study, we found that among ADHD group 88% showed combined presentation (ADHD-CT), 8% showed predominantly inattentive presentation (ADHD-PI), 4% showed predominantly hyperactive presentation (ADHD-H). This is in line with clinic samples prevalence which reported ADHD-CT is approximately one and one half times more prevalent than ADHD-PI. Although ADHD-PI appears to be more prevalent in the general population, children diagnosed with ADHD-CT are more likely to be referred for treatment probably reflecting the greater amount of disruptive behavior associated with the ADHD-CT symptoms [12].
In ASD group, 32% (N = 8) had mild-to-moderate presentation, 68% (N = 17) had severe presentation. This is consistent with Nguyen et al. 2021 who found more Vietnamese children were diagnosed with severe autism (59.4%) than mild and moderate autism [13].
In this study, there was no statistically significant difference in mean neopterin level between controls and both ASD and ADHD group. This is inconsistent with Zhao et al. 2015 who studied neopterin level among 80 patients with autism and 80 typically matched healthy participants and Sweeten et al. 2003 who measured neopterin level among 23 participants with autism and 21 healthy subjects. In both previously mentioned studies, plasma neopterin levels were significantly higher in the autistic group than in the comparison subjects [14, 15]. Also inconsistent with Ceylan et al. 2014 who found that neopterin levels were significantly higher in the ADHD group than in the comparison subjects [16]. This inconsistency may reflect the need for further studies among those patients with multiple sampling and genetic assessments to detect role of neopterin and other immunologic markers.
In this study, no statistically significant difference was found between mean neopterin levels in ADHD subtypes. This is consistent with Ceylan et al. 2014 who found no significant differences in neopterin levels among the subtypes of ADHD [16].
There was no statistically significant difference in mean neopterin level in relation with severity of ASD symptoms. This is inconsistent with Zhao et al. 2015 who reported a significant positive association between plasma neopterin levels and CARS scores [15].
There is statistically significant difference in mean neopterin level in younger ages of ASD group. This may suggest that immune system activation may occur early in the course of the disease. This is supported by Mazzone et al. 2018 who suggested that neuroanatomical and neurochemical events occur relatively early in the development of the central nervous system (CNS), this may help in early pharmacological intervention that helps to cure and maybe even preclude some of the severe behavioral symptoms of ASD [17].
Limitations of the study
Neopterin level was measured in plasma, not in cerebral spinal fluid. It is still uncertain whether peripheral neopterin levels could reflect similar changes in the central nervous system. Without serial measurement of the circulating neopterin levels, this study yielded no data regarding when and how the levels changed in these children.