This study aimed to compare the salivary cortisol level of ADHD children versus healthy children. Also, it aimed to compare salivary cortisol level of ADHD children before treatment and one month after treatment with methylphenidate. At the present study, sixty children were selected for both groups aged from 6 to 12 years in agreement with the study of Liang-Jen et al. [13] concerning age and because methylphenidate was recommended to be prescribed for children aged 6 years and older [1].
ADHD children who participated in the study were non-medicated, newly diagnosed, methylphenidate-prescribed and free from chronic diseases and psychiatric disorders other than ADHD, and control children were healthy and free from chronic diseases and psychiatric disorders. These criteria were selected to attribute any difference before treatment to the presence of the disorder itself, not to the effect of the medication, and also to determine the effect of methylphenidate on salivary cortisol level of ADHD children.
Unstimulated salivary samples were collected because salivary samples are less invasive and not as painful as blood samples. Also, unstimulated salivary samples are more comfortable, less invasive, and more accurate than stimulated salivary samples [15, 16]. Salivary samples were stored at − 20 °C according to the manufacturer’s instructions. Then, they were sent for laboratory analysis using the ELISA kit.
In this study, 76.7% of the examined children were males, and 23.3%were females in each group. ADHD is more common in males than in females. Many previous studies reported male to female ratio in ADHD as 2.5:1 [4], 8:1 [17], and 5:1 [18].
Concerning salivary cortisol level, this study demonstrated that the ADHD group had a statistically significant decrease in salivary cortisol level than the control group in agreement with the studies of Enrique et al. [19], Catia et al. [20], and Johan et al. [21].
The study of S.Himani et al. [10] concluded that salivary cortisol level was lower in ADHD/ODD children not taking stimulant drugs than in normal controls. Also, the study of Liang et al. [22] reported that ADHD children had a significantly lower plasma cortisol level compared to the control group. These results supported the possibility of dysfunction of the HPA axis in ADHD children.
On the contrary, the results of the present study disagreed with the results of the studies of Liang-gen et al. [12] and Alkhodier et al. [14] which showed no difference in salivary cortisol level between the ADHD and control groups. This difference might be due to the differences in sample size, the study of Alkhodier et al. [14], and the number of the examined non-medicated ADHD children and normal children was 17. Also, the study of Hanna et al. [23] revealed no significant difference between the ADHD and control groups regarding salivary cortisol levels, but 37.1% of ADHD children were on stimulant medication.
The results of comparing salivary cortisol level between the ADHD subtypes and the control group revealed that the hyperactive/impulsive (HI) ADHD subtype had a statistically significant decrease of salivary cortisol level compared to the control group in agreement with the study of Blomqvist et al. [24] which confirmed that HI ADHD had a significantly reduced salivary cortisol level 30 min after awaking compared to the control group. Also, this study showed no statistically significant difference in salivary cortisol level between the inattentive (I) ADHD subtype and the control group in agreement with the study of William et al. [11] which showed no significant difference between the moderately inattentive, threshold inattentive, and control groups regarding salivary cortisol level at baseline.
The present study reported no statistically significant difference between the combined (C) ADHD subtype and the control groups and between the 3 ADHD subtypes regarding salivary cortisol. The descending order of salivary cortisol level between the 3 ADHD subtypes was ADHD-HI then ADHD-C then ADHD-I (p = 0.036, 0.064, 0.562, respectively). However, the study of Liang et al. [22] concluded that the 3ADHD subtypes had significantly lower cortisol levels than the control group, and the descending order of the cortisol level in the plasma was in ADHD-HI, ADHD-I, and then ADHD-C, and there was no significant difference between the ADHD-I and ADHD-C groups. These results support the possibility that HPA axis dysfunction in ADHD children is related to hyperactivity more than inattention.
At the present study, salivary cortisol level was measured for 60 ADHD children before treatment and 45 ADHD children after treatment at the second visit because of drop out cases. At the study of Liang-Jen et al. [13], the salivary cortisol was measured for 50 ADHD children before treatment and 42 ADHD children after treatment at the second visit. At the present study, the dose of methylphenidate was prescribed for ADHD children according to age, weight, and severity of symptoms in agreement with clinical guidelines for prescribing methylphenidate for ADHD children.
Concerning the effect of 1-month treatment with methylphenidate on salivary cortisol level of ADHD children, the present study showed that salivary cortisol level of ADHD children had a statistically significant increase after 1-month treatment with methylphenidate compared to before treatment in agreement with Liang-Jen et al. [13] supporting the possibility that methylphenidate intake positively affects the function of HPA axis in ADHD children. The inattentive subtype, hyperactive/impulsive subtype, and combined subtype showed no significant difference after treatment compared to before treatment (p = 0.068, 0.06, 0.717, respectively). Also, the study of Moon-Soo et al. [25] revealed that plasma cortisol levels had not changed significantly after a 12-week treatment with methylphenidate or bupropion in combined ADHD children.
The result of this study demonstrated that there was no statistically significant difference in salivary cortisol level between the ADHD and control groups, between the ADHD-HI, ADHD-I, ADHD-C, and control groups and between the 3 ADHD subtypes after 1-month treatment with methylphenidate. The study of S.Himani et al. [10] showed that ADHD/ODD patient who had taken stimulants either methylphenidate or D-amphetamine had salivary cortisol levels that are not significantly different from normal individuals. Also, the study of Alkhodier et al. [14] showed that salivary cortisol levels did not differ significantly between the control group and the medicated ADHD group.