Giana Grazia, Romano Emilia, Porfirio Maria Cristina, D'Ambrosio Roberto, Giovinazzo Silvia, Troianiello Miriam, Barlocci Eleonora, Travaglini Domenica, Granstrem Oleg, Pascale Esterina, Tarani Luigi, Curatolo Paolo, Laviola Giovanni, Adriani Walter
Child Neuro-Psychiatry Unit, University of "Roma 2" Tor Vergata, Rome, Italy; Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Cell Biology & Neurosciences Dept., Istituto Superiore di Sanità, Rome, Italy; Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
J Neuroimmunol. 2015 Jan 15;278:212-22. doi: 10.1016/j.jneuroim.2014.11.008. Epub 2014 Nov 18.
Interest is rising for auto-immune contribution in neuro-psychiatry. We evaluated the auto-antibodies against dopamine transporter (DAT aAbs) in 61 children (46 ADHD who met DSM-IV-TR criteria, 15 healthy controls).
ADHD patients were assigned, according to severity, either to a non-pharmacological therapy (NPT, N=32) or to a pharmacological treatment (PT, N=14) with methylphenidate (MPH). In ADHD children, blood samples were withdrawn twice, at recruitment (T0 basal) and after 6 weeks (T1); following 16 excluded subjects, DAT genotype was characterized (9-repeat or 10-repeat alleles; N=15 each). After 18 months of NPT or PT, some patients (carrying at least one 9-repeat allele) were blood sampled again (T2), for comparison with healthy controls (final n=8) RESULTS: Compared to NPT, basal DAT aAbs titers were higher within most severe patients (then assigned to PT), specifically if carrying a DAT 10/10 genotype. DAT aAbs levels of NPT group resulted highly correlated with distinct subscales of Conners' Parent/Teacher Scales (Rs>0.34), especially within DAT 10/10 genotype (Rs>0.53). While T1 titers were elevated over T0 baseline for NPT children, such an increase was not observed in PT patients carrying at least one 9-repeat allele, who also showed behavioral response to subchronic MPH. After 12-24 months of MPH exposure, DAT aAbs titers in PT subjects were comparable to those of healthy controls, while titers remained significantly elevated in NPT patients. Data warrant further research on serum DAT aAbs, which could be used to confirm ADHD diagnosis and/or to monitor therapeutic efficacy of MPH.
自身免疫在神经精神病学中的作用正日益受到关注。我们评估了61名儿童(46名符合DSM-IV-TR标准的注意力缺陷多动障碍患者,15名健康对照)体内抗多巴胺转运体自身抗体(DAT aAbs)的情况。
根据严重程度,注意力缺陷多动障碍患者被分为非药物治疗组(NPT,N = 32)或接受哌甲酯(MPH)药物治疗组(PT,N = 14)。在注意力缺陷多动障碍儿童中,在招募时(T0基线)和6周后(T1)采集两次血样;在排除16名受试者后,对DAT基因型进行了特征分析(9重复或10重复等位基因;每组N = 15)。在接受18个月的非药物治疗或药物治疗后,一些患者(携带至少一个9重复等位基因)再次采集血样(T2),以便与健康对照进行比较(最终n = 8)。结果:与非药物治疗组相比,最严重的患者(随后被分配到药物治疗组)体内基础DAT aAbs滴度更高,特别是携带DAT 10/10基因型的患者。非药物治疗组的DAT aAbs水平与Conners父母/教师量表的不同子量表高度相关(Rs>0.34),特别是在DAT 10/10基因型患者中(Rs>0.53)。虽然非药物治疗组儿童的T1滴度比T0基线升高,但在携带至少一个9重复等位基因的药物治疗组患者中未观察到这种增加,这些患者对亚慢性MPH也有行为反应。在接受MPH治疗12 - 24个月后,药物治疗组受试者的DAT aAbs滴度与健康对照相当,而非药物治疗组患者的滴度仍显著升高。这些数据表明需要对血清DAT aAbs进行进一步研究,其可用于确诊注意力缺陷多动障碍和/或监测MPH的治疗效果。