Review Neuroimmunomodulation 2018;25:328–333 A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder Douglas Teixeira Leffa a, b Iraci L.S. Torres a, b Luis Augusto Rohde c, d a Post-Graduate Program in Medicine, Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; b Laboratory of Pain Pharmacology and Neuromodulation, Preclinical Studies, Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; c ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; d National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, Brazil Received: March 1, 2018 Accepted after revision: April 26, 2018 Published online: June 6, 2018 Luis Augusto Rohde Serviço de Psiquiatria da Infância e Adolescência Hospital de Clínicas de Porto Alegre, 4º andar Rua Ramiro Barcelos 2350, Porto Alegre 90035-003 (Brazil) E-Mail lrohde @terra.com.br © 2018 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/nim DOI: 10.1159/000489635 Keywords Attention-deficit/hyperactivity disorder · Inflammation · Neuronal damage · Biomarkers Abstract Attention-deficit/hyperactivity disorder (ADHD) is a preva- lent neurodevelopmental condition that impairs quality of life in social, academic, and occupational contexts for both children and adults. Although a strong neurobiological basis has been demonstrated, the pathophysiology of ADHD is still poorly understood. Among the proposed mechanisms are glial activation, neuronal damage and degeneration, in- creased oxidative stress, reduced neurotrophic support, al- tered neurotransmitter metabolism, and blood-brain barrier disruption. In this way, a potential role of inflammation has been increasingly researched. However, evidence for the in- volvement of inflammation in ADHD is still scarce and comes mainly from (1) observational studies showing a strong co- morbidity of ADHD with inflammatory and autoimmune dis- orders; (2) studies evaluating serum inflammatory markers; and (3) genetic studies. A co-occurrence of ADHD with in- flammatory disorders has been demonstrated in a large number of subjects, suggesting a range of underlying mech- anisms such as an altered immune response, common ge- netics, and environmental links. The evaluation of serum in- flammatory markers has provided mixed results, likely due to the small sample sizes and high heterogeneity between biomarkers. However, there is evidence that increased in- flammation during the early development may be a risk fac- tor for ADHD symptoms. Although genetic studies have demonstrated a potential role for inflammation in this disor- der, there is no clear evidence. To sum up, inflammation may be an important mechanism in ADHD pathophysiology, but more studies are still needed for a more precise conclusion. © 2018 S. Karger AG, Basel Epidemiology Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by the im- pairing symptoms of inattention and/or hyperactivity/ impulsivity [1]. A meta-analysis published in 2007 has demonstrated that the worldwide prevalence of ADHD in Iraci L.S. Torres and Luis Augusto Rohde contributed equally to this work.