ADHD, ODCD, Spence and CDI scores, and baseline and post-treatment groups are shown in Table 1. ADHD remitted in 73.3% of participants after treatment with MPH, as reported by parents (NICHQ Vanderbilt scores).
Table 1
ADHD Presentation, CDI, and SCAS scores for the ADHD group before and after treatment
| Baseline ADHD (n = 31) | Post-treatment ADHD (n = 31) | Statistics |
t | p |
Attention Deficit (AD) | 17,48 ± 4,42 | 5,38 ± 4,25 | 10,99 | 0,00001*** |
Combined ADHD (C) | 13,19 ± 8,92 | 3,59 ± 4,29 | 5,4 | 0,00001*** |
OD Conduct Disorder (ODCD) | 10,55 ± 7,24 | 4,25 ± 6,16 | 3,69 | 0,0005*** |
CDI_total score | 10,2 ± 5,63 | 7,69 ± 3,05 | 2,18 | 0,03* |
Anxiety total score (SCAS) | 30,42 ± 15,49 | 16,93 ± 13,15 | 3,7 | 0,0005*** |
Data are expressed as the mean ± SD (standard deviation). Attention deficit and combined ADHD and opositional defiant conduct disorder: total punctuaction scores of each Vanderbilt subscale CDI (Childhood Depression Inventory); anxiety total score: SCAS Spence scale.
Pro-inflammatory cytokines.
Interleukin-1beta (IL-1beta).
We found a statistically significant difference (F = 5.39, p = 0.025) depending on sex, with a much higher concentration (and much higher dispersion of the data) of IL-1 in men (2.49 ± 3.9) vs. women (0.22 ± 0.15 pg/ ml).
Comparison between Moments. In the entire sample, the concentration of IL-1beta (Table: 2) was not different between the baseline and post-treatment) of ADHD.
Table 2
Interleukins values in the plasma ADHD group before and after methylphenidate treatment.
Interleukins | Inattentive ADHD (n = 13) | Combined ADHD (n = 18) |
Baseline | Post-MPH | Baseline | Post-MPH |
Pro-inflammatory | IL-1beta | 2,26 ± 3,91 | 2,83 ± 4,17 | 1,55 ± 3,41 | 1,72 ± 3,35 |
IL-5 | 14,96 ± 18,21 | 17,83 ± 26,32 | 17,36 ± 32,21 | 9,21 ± 14,65 |
IL-6 | 35,75 ± 67,13 | 37,38 ± 89,61 | 15,41 ± 24,85 | 10,81 ± 19,96 |
TNFalpha | 4, 39 ± 4,75 | 7,00 ± 10,19 | 4,03 ± 2,55 | 7,49 ± 8,24 |
Anti-inflammatory | IL-4 | 14,25 ± 18,04 | 17, 95 ± 29,13 | 7,29 ± 11,25 | 7,23 ± 10,48 |
IL-10 | 2,49 ± 2,95 | 2,27 ± 2,87 | 1,16 ± 1,63 | 1,77 ± 2,15 |
IL-13 | 4,54 ± 7,04 | 2,89 ± 5,29 | 2,08 ± 4,52 | 3,49 ± 6,09 |
Values are expressed as the mean (standard deviation). MPH, methylphenidate.
Comparison by Presentations/TCOD. There were no differences in the concentration of IL-1 between both presentations (ADHD-AD and ADHD-C). However, the concentration of IL-1beta was much higher in ADHD-AD with comorbid TCOD (6.46 ± 4.86 pg/ml) and reached a high statistical significance (F = 7.86, p = 0.01); Fig. 1. In ADHD-C with comorbid TCOD, we observed a contrasting profile, although without statistical differences.
Factorial analysis. To explain the concentration of IL-1beta, the factor analysis including all the factors analyzed reached statistical significance (F = 3.15, p = 0.02) due to the form of presentation (F = 7.26, p = 0.01), with interaction between the three Factors (F = 6.1, p = 0.006).
Interleukin-5 (IL-5).
There is a higher concentration of IL-5 in men, although there are no significant differences due to the great dispersion of the data.
Comparison between Moments. Although after treatment with methylphenidate we observed a decrease in the mean concentration (with less dispersion of the data) of IL-5, no statistical differences were observed between the basal concentration (16.36 ± 26.78 pg/ml) and post-treatment (12.80 ± 20.28 pg/ml) (F = 0.27, p = 0.6).
Comparison by Presentation There were also no differences in the concentration of IL-5 in the response to pharmacological treatment between both presentations of ADHD.
Comparison by Presentations/TCOD. The basal concentration profile of IL-5 was opposite between the two presentations, with a higher concentration in ADHD-AD in the presence of TCOD [29.52 ± 21.20 vs 10.78 ± 20.64 pg/ml, in the absence of TCOD), (F = 4.4, p = 0.05)]; and higher concentration in the absence of TCOD in ADHD-C (21.69 ± 37.57 vs 8.62 ± 13.14 pg/ml, in the presence of TCOD). In ADHD-C, there was no statistical difference in the concentration of IL-5 between both presentations depending on the TCOD factor.
Factorial analysis. The factor analysis including the set of factors analysed confirmed the significant difference (F = 5.9, p = 0.02) due to a higher concentration of IL-5 in ADHD-AD.
Interleukin-6 (IL-6).
Due to the very high dispersion of the data, we only found statistically significant differences between both sexes (F = 3.54; p = 0.07) due to the much higher concentration in men (28.26 ± 58.66; vs 2.45 ± 1.31 pg/ml in women ).
Comparison between Moments. There were no differences between the basal concentration and post-treatment concentration of IL-6, both due to similar mean concentrations and with similar variances.
Comparison by Presentation Both the mean concentration and variance were more than two times higher in patients with ADHD-AD than in those with ADHD-C (36.56 ± 77.06; vs 13.11 ± 22.24 pg/ml).
Comparison by Presentations/TCOD. The presence of TCOD symptoms did not cause statistically significant differences between both ADHD presentations in IL-6 concentration [39.01 ± 91.24 vs 30.84 ± 29.45 in ADHD-AD without/with TCOD; 19.51 ± 28.67 vs 9.55 ± 17.69 in ADHD-C without/with TCOD]. In both cases, the dispersion of the data prevented the detection of significant differences.
Factorial analysis. The analysis of the set of factors analyzedanalysed to explain the changes in the concentration of IL-6, only the ADHD-AD Presentation reaches statistical significance (F = 5.62, p = 0.02).
Tumoral Necrosis Factor – Alpha (TNFα).
There were no differences between the sexes in the concentration of TNFα.
Comparison between Moments. There were no statistically significant differences, although post-treatment the concentration of TNFα almost doubles its average concentration, with even greater dispersion of the data; 4.18 ± 3.55, baseline; 7.29 ± 8.89 pg/ml post-treatment.
Comparison by Presentation Between the two presentations of ADHD [5.7 ± 7.85 in ADHD-LD; vs 5.76 ± 6.24 pg/ml, in ADHD-C], there were also no significant differences for TFNα, with very similar concentrations and wide standard deviations.
Comparison by Presentations/TCOD. In the presence of TCOD symptoms, the concentration is very similar at both times. However, according to Presentations, the TNFα profile is opposite, mirror image: 4.66 ± 5.69 vs 8.13 ± 11.84 pg/ml, without/with TCOD in ADHD-AD; 8.39 ± 9.47 vs 4.30 ± 2.82 pg/ml, in ADHD-C without/with TCOD; without statistical differences.
Factorial analysis. The model that includes the set of factors analysed reaches statistical significance (F = 4.08, p = 0.047).
Anti-inflammatory cytokines.
Interleukin-4 (IL-4).
There were no differences in IL-4 concentration depending on sex.
Comparison between Moments. There were no differences in the concentration of IL-4 induced by methylphenidate.
Comparison by Presentation Despite the very wide difference in mean concentration of IL-4, greater in ADHD-AD (16.1 ± 23.66 mg/ml; vs 7.26 ± 10.66 pg/ml in ADHD-C), the very wide dispersion of the data also prevents statistical significance (F = 2.3, p = 0.14) between both ADHD presentations.
Comparison by Presentations/TCOD. In the presence of TCOD in ADHD-AD, the concentration of IL-4 (24.1 ± 16.1 pg/ml) doubled that observed in ADHD-AD in the absence of TCOD (12.7 ± 26.01 pg/ml), reaching statistical significance (F = 4.6, p = 0.046). In ADHD-C, the presence of TCOD did not modify the concentration of IL-4, even with an inverse profile (higher concentration in the absence of TCOD) to ADHD-AD, without significant differences.
Factorial analysis. Including the set of factors analysed the increase in IL-4 in patients with ADHD-LD reached a very high significance (F = 10.3, p = 0.003), with a statistically significant influence of the TCOD factor.
Interleukin-10 (IL-10).
Although the mean concentration of IL-10 in men is approximately double that in women (2.09 ± 2.58 vs 0.9 ± 0.38 pg/ml; respectively), the difference does not reach statistical significance because of the wide dispersion of the data.
Comparison between Moments. There were no differences between the baseline concentration of IL-10 (1.71 ± 1.79 pg/ml) and the concentration after treatment for this anti-inflammatory cytokine.
Comparison by Presentation The concentration of IL-10 was slightly higher (without statistical differences) in ADHD-AD (2.37 ± 2.83 pg/ml; vs 1.47 ± 1.9 in ADHD-C).
Comparison by Presentations/TCOD. In the presence of TCOD, the concentration of IL-10 was higher in ADHD-AD, with statistically significant differences [3.93 ± 3.06, in the presence of TCOD, 1.70 ± 2.56 pg/ml, in the absence of TCOD; F = 4.7, p = 0.04]. The IL-10 concentration profile was inverse in ADHD-C: 1.21 ± 1.44 pg/ml with TCOD vs 1.93 ± 2.55 pg/ml without TCOD.
In the absence of anxiety symptoms, the concentration of IL-10 was practically identical in both presentations (1.74 ± 2.34 pg/ml) and was much higher in the presence of anxiety, especially in inattentive ADHD (4.1 ± 3.71 pg/ml). The very small number of patients and the wide dispersion of the data prevent conclusions from being drawn.
Factorial analysis. The model that includes the three factors analysed is at the limit of statistical significance (F = 2.32, p = 0.07), with differences due to the TCOD factor; the interaction between the three factors is significant (F = 4.85, p = 0.015). In the factor analysis segregating by presentation, the concentration of IL-10 was closely related to the presence of TCOD symptoms, but only in patients with inattentive ADHD (F = 5.8, p = 0.02).
Interleukin-13 (IL-13)
There was a higher concentration of IL-13 in men, which did not reach statistical significance.
Comparison between Moments. There were no differences between the basal concentration and post-treatment concentration of IL-13, with similar mean concentrations and with a wide dispersion of the data.
Comparison by Presentation At baseline, the concentration of IL-13 in ADHD-AD (4.54 ± 7.04 pg/ml) doubled that observed in ADHD-C (2.09 ± 4.52 pg/ml). In the post-treatment instant, these differences between both presentations disappear, bringing the means and standard deviations closer together. We observed a decrease in Il-13 in ADHD-AD, parallel to an increase in ADHD-C. The very wide standard deviations preclude statistical significance.
Comparison by Presentations/TCOD. The concentration of IL-13 was lower in the group of patients in the absence of TCOD symptoms, [2.54 ± 4.76; vs 3.81 ± 6.41 pg/ml pg/ml, with TCOD], without significant differences. The concentration profile was opposite between both presentations: higher concentration in the presence of TCOD in ADHD-AD (9.47 ± 9.13 pg/ml; (F = 9.82, p = 0.006), Fig. 2, and higher concentration in the absence of TCOD in ADHD -C (4.35 ± 7.09 pg/ml; p = NS).
Factorial analysis. With a significant interaction between the factors analysed (F = 4.97, p = 0.01), the concentration of IL-13 was related to the presence of TCOD symptoms in ADHD-AD. These differences disappear after treatment, and the interaction between factors also disappears.