title: [Immunological and endocrinological pattern in ADHD etiopathogenesis].
abstract: Attention-Deficit Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder among children. There are 3 subtypes of ADHD: (1) with prevalent inattentive symptoms (2) with prevalent hyperactive-impulsive symptoms and (3) the combined subtype. It typically manifests itself before age 7 years and occurs more frequently in boys than in girls. It is diagnosed when the hyperactivity, impulsiveness and inattention last long, appear at least in two environments and their intensity impairs the functioning of the child. The etiology of ADHD is not well-known but recent studies have shown that genetic factors are of big importance. Also several environmental influences that raise the risk for ADHD development have been identified. Recently, it has been postulated that the reduced activity of the dopaminergic and noradrenergic systems play a crucial role in ADHD pathogenesis. It is evidenced by the fact that drugs intensifying the noradrenergic and dopaminergic transmission are the most successful for ADHD treatment. At present, it has been also postulated that the disturbances in endocrine and immune systems are involved in the ADHD pathogenesis. Interconnections between functions of these systems and function of neurotransmitters are better recognized now and show that disturbances in their cooperation can be involved in some psychiatric disorders. In the case of ADHD, most data are related to disturbances in the activity of the hypothalamus-pituitary-adrenal (HPA) axis activity. In particular, the lower level of cortisol in children with ADHD, especially in the hyperactive-impulsive type ADHD, the disturbance in the circadian rhythm of this steroid and the lack of its inhibition by the dexamethasone have been documented. Many clinical data indicate that in children with ADHD, the psychological stress evokes a weaker activation of the HPA axis than in the control group. Epidemiological and preclinical investigations have shown that the disturbance in the HPA axis in ADHD can result from an excessive exposure to glucocorticoids in the fetal and early postnatal periods. Glucocorticoid administration in this period of life can provoke permanent changes in the level of brain glucocorticoid receptors and, in consequence, dysregulation of HPA axis activity, disturbances in biosynthesis of the neurotransmitters and their receptors and changes in the intracellular pathways. Glucocorticoids are known to intensify the dopaminergic system activity, so the decrease in their expression in ADHD can cause the hypofunction of this system. Since the attention and motor activity disorders often occur in children with generalized resistance to thyroid hormones, their role in ADHD pathogenesis was evaluated. However, most of the studies indicated that the levels of triiodothyronine (T3), thyroxine (T4), the free thyroxine, and the thyroid stimulating hormone (TSH) did not change in ADHD. Preclinical data concerning the role of androgens in the ADHD pathogenesis suggest that the elevated testosterone level can diminish the brain blood flow in the frontal cortex, via lowering of the level of estrogen receptor-alpha and the vascular endothelial growth factor (VEGF), and in consequence disturb processes of the memory. The association between ADHD and the polymorphism of the gene coding for androgen receptor, which leads to its higher expression has been found, however, the issue of the androgen participation in the ADHD pathogenesis is still poorly recognized. Frequent co-occurrence of ADHD and allergic diseases and correlation between ADHD and streptococcus-mediated neuropsychiatric disorders suggest the participation of the immune system in the ADHD pathogenesis. Also experimental data from an animal model of ADHD showed changes in the expression in at least several essential genes for the immune system function. However, on the other hand, the lack of the association between asthma and immunoglobulin E- dependent athopic reaction and the lack of the elevated anti-ganglia antibodies in ADHD speaks against the implication of autoimmunity in ADHD pathogenesis. Since psychostimulants, the most therapeutically efficient drugs in ADHD, not only increase the level of the dopamine and norepinephrines but also increase the activity of the HPA axis and reduce the concentration of androgens, it cannot be excluded that their beneficial effect can partly issue from a normalizing action on hormonal levels. However, currently available clinical and experimental data do not permit precise estimation of the role of endocrine and immune systems in the pathogenesis of ADHD and in therapeutic action of psychostimulants.
authors: Zakład Neuroendokrynologii Doświadczalnej, Instytut Farmakologii Polskiej Akademii Nauk w Krakowie. budzisz@if-pan.krakow.pl
authors: Bogusława
authors: B
authors: Budziszewska
authors: Agnieszka
authors: A
authors: Basta-Kaim
authors: Marta
authors: M
authors: Kubera
authors: Władysław
authors: W
authors: Lasoń
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D015984:Causality; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D004700:Endocrine System Diseases / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D017678:Sex Distribution; D012737:Sex Factors
chemical_list: D000697:Central Nervous System Stimulants