Detection of auto-antibodies to DAT in the serum: Interactions with DAT genotype and psycho-stimulant therapy for ADHD

Giana, G.; 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

doi:10.1016/j.jneuroim.2014.11.008

Cited by 39 publications

(36 citation statements)

References 73 publications

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“…These results have been replicated in a following study [44], and the authors also demonstrated that ADHD patients had increased serum levels of interleukin 6 (IL-6) and IL-10. Increased levels of antibasal ganglia antibodies [45] and antibodies against the dopamine transporter [46] have also been detected in ADHD, supporting the role of the immune system in the disorder.…”

Section: Biochemical Markersmentioning

confidence: 85%

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder

Leffa

Torres

Rohde

2018

Neuroimmunomodulation

122

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Attention-deficit/hyperactivity disorder (ADHD) is a prevalent 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, increased oxidative stress, reduced neurotrophic support, altered neurotransmitter metabolism, and blood-brain barrier disruption. In this way, a potential role of inflammation has been increasingly researched. However, evidence for the involvement of inflammation in ADHD is still scarce and comes mainly from (1) observational studies showing a strong comorbidity of ADHD with inflammatory and autoimmune disorders; (2) studies evaluating serum inflammatory markers; and (3) genetic studies. A co-occurrence of ADHD with inflammatory disorders has been demonstrated in a large number of subjects, suggesting a range of underlying mechanisms such as an altered immune response, common genetics, and environmental links. The evaluation of serum inflammatory markers has provided mixed results, likely due to the small sample sizes and high heterogeneity between biomarkers. However, there is evidence that increased inflammation during the early development may be a risk factor for ADHD symptoms. Although genetic studies have demonstrated a potential role for inflammation in this disorder, 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.

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Section: Biochemical Markersmentioning

confidence: 85%

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder

Leffa

Torres

Rohde

2018

Neuroimmunomodulation

122

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“…McGough et al () and Zeni et al () found no significant association between specific genes and occurrence of adverse events. Except two studies (Giana et al, ; Kirley et al, ), other researchers reported the acceptability of MPH as more than 90% (mean: 97.2%).…”

Section: Resultsmentioning

confidence: 92%

“…To the best of our knowledge, our meta‐analysis was the first to investigate 9R homozygosity in response to MPH among children with ADHD. Moreover, greater number of studies on children are now available (Giana et al, ; Hong et al, ; Kim, Sharma, & Ryan, ; Pasini et al, ; Ray et al, ; Stein et al, ). Apparently, a review of more recent studies is required to enhance the existing knowledge and clarify the observed inconsistencies regarding the association between the SLC6A3 VNTR and clinical response to MPH in children with ADHD.…”

Section: Introductionmentioning

confidence: 99%

SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta‐analysis

Soleimani

Salehi

Soltanipour

et al. 2017

American J of Med Genetics Pt B

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Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta-analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta-analysis was conducted using a random-effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta-regression were performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta-analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: -0.43). In the meta-regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta-analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended.

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“…These findings link post infectious autoimmunity to the onset of both OCD and ADHD. Giana et al found elevated IgG autoantibody titers against DAT in the serum of ADHD children by ELISA (n = 61) [153], which again suggests that the dysregulation in the levels of dopamine neurotransmitter may be caused by autoantibodies in these disorders.…”

Section: Obsessive-compulsive Disorder (Ocd) and Attention-deficit/hymentioning

confidence: 97%

Autoantibodies in Neuropsychiatric Disorders

et al. 2016

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Abstract:Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-D-aspartate receptor (NMDA-R), which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition. In recent years, a wide range of neuropsychiatric diseases and autoantibodies targeting ion-channels or neuronal receptors including NMDA-R, voltage gated potassium channel complex (VGKC complex), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R), γ-aminobutyric acid receptor (GABA-R) and dopamine receptor (DR) were studied and conflicting reports have been published regarding the seroprevalence of these autoantibodies. A clear causative role of autoantibodies on psychiatric symptoms has as yet only been shown for the NMDA-R. Several other autoantibodies have been related to the presence of certain symptoms and antibody effector mechanisms have been proposed. However, extensive clinical studies with large multicenter efforts to standardize diagnostic procedures for autoimmune etiology and animal studies are needed to confirm the pathogenicity of these autoantibodies. In this review, we discuss the current knowledge of neuronal autoantibodies in the major neuropsychiatric disorders: psychotic, major depression, autism spectrum, obsessive-compulsive and attention-deficit/hyperactivity disorders.

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Detection of auto-antibodies to DAT in the serum: Interactions with DAT genotype and psycho-stimulant therapy for ADHD

Cited by 39 publications

References 73 publications

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder

SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta‐analysis

Autoantibodies in Neuropsychiatric Disorders

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