Attention deficit and hyperactivity disorder scores are elevated and respond to N-acetylcysteine treatment in patients with systemic lupus erythematosus

Abstract

Objective: To investigate whether attention deficit hyperactivity disorder (ADHD) may serve as a marker of neuropsychiatric disease and as a target for N-acetylcysteine (NAC) treatment in patients with systemic lupus erythematosus (SLE).

Methods: The ADHD Self-Report Scale (ASRS) was used to assess 49 patients with SLE and 46 matched healthy control subjects. Twenty-four of the patients with SLE were randomized to receive either placebo, NAC at a dosage of 2.4 gm/day, or NAC at a dosage of 4.8 gm/day. Disease activity was evaluated monthly using the British Isles Lupus Assessment Group (BILAG) index, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Fatigue Assessment Scale (FAS), and the ASRS, before and during the 3-month treatment period and after a 1-month washout period.

Results: The cognitive/inattentive (ASRS part A), hyperactivity/impulsive (ASRS part B), and combined (total) ASRS scores were increased in patients with SLE compared with control subjects (mean ± SEM 17.37 ± 1.03 [P = 3 × 10(-7) ], 14.51 ± 0.89 [P = 2 × 10(-4) ], and 31.92 ± 1.74 [P = 8 × 10(-7) ], respectively, versus 10.41 ± 1.02, 9.61 ± 1.21, and 20.02 ± 1.98, respectively. ASRS part A scores correlated with SLEDAI (r = 0.53, P < 0.0001) and BILAG scores (r = 0.36, P = 0.011). ASRS total scores also correlated with SLEDAI (r = 0.45, P = 0.0009) and BILAG scores (r = 0.31, P = 0.025). ASRS part A (r = 0.73, P < 0.0001), ASRS part B (r = 0.47, P = 0.0006), and ASRS total scores (r = 0.67, P < 0.0001) correlated with the FAS score. Relative to the scores in placebo-treated patients, ASRS total scores were reduced in SLE patients treated with NAC dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.037). ASRS part A scores were reduced by NAC dosages of 2.4 gm/day (P = 0.001) and 4.8 gm/day (P < 0.0001) as well as by NAC at dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.001).

Conclusion: In patients with SLE, elevated ASRS scores reveal previously unrecognized and clinically significant symptoms of ADHD that respond to NAC treatment.

Figure 1

Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS) part A (cognitive/inattentive), ASRS part B (hyperactivity/impulsive), and total ASRS scores in patients with systemic lupus erythematosus (SLE) and healthy control subjects matched for age within 10 years, sex, and ethnicity. Left, Analysis of cohort 1, comprising 24 patients with SLE and 22 healthy control subjects. Middle, Analysis of cohort 2, comprising 25 patients with SLE and 24 healthy control subjects. Right, Analysis of cohorts 1 and 2 combined. Bars show the mean ± SEM. * = P < 0.05 by unpaired 2-tailed t-test.

Figure 2

Correlation of ASRS part A and ASRS part B scores with the SLE Disease Activity Index (SLEDAI), the British Isles Lupus Assessment Group (BILAG) index, and the Fatigue Assessment Scale (FAS) in 49 patients with SLE. Pearson’s correlation coefficients are shown for correlations with P values less than 0.05. See Figure 1 for other definitions.

Figure 3

Effect of N-acetylcysteine (NAC) and placebo on ASRS total scores and ASRS part A scores in 24 patients with SLE treated with placebo (n = 6), NAC dose 2 (2.4 gm/day; n = 9), NAC dose 3 (4.8 gm/day; n = 9), or NAC all doses (doses 2 and 3 combined; n = 18). Values are the mean ± SEM. P values indicate comparisons of pretreatment values (visit 1) with values after 1 month (visit 2), 2 months (visit 3), 3 months (visit 4), or 4 months (visit 5 [3 months of treatment followed by a 1-month washout period]), determined by paired 2-tailed t-test. See Figure 1 for other definitions.