Etiology and pathogenesis of Attention‐deficit Hyperactivity Disorder (ADHD): significance of prematurity and perinatal hypoxic‐haemodynamic encephalopathy

Abstract

Attention-deficit Hyperactivity Disorder (ADHD), defined as a disorder of awareness with impulsivity, has lately been characterized as a dysfunction of the striatum (neostriatum = globus pallidus + putamen). This structure is in a unique position of contextual analysis and samples information samples information from almost the entire cortex through its spiny neurons. The etiology is heterogeneous, with genetic as well as lesional factors. Among the latter, pre- and perinatal events are prominent. Advances in the understanding of the role of fetal circulatory insufficiency with loss of autoregulation and systemic hypotension have drawn attention to the vulnerability of watershed regions, including the striatum. Not only circulatory facts are important for this selectivity, however. The anatomical characteristics, with convergent glutaminergic afferent synaptic transmission from almost the entire cortex contribute to the vulnerability in ischemia-induced liberation of glutamate: The striatum becomes the victim of its virtue. Repeated hypoxic-ischemic events are particularly common in prematurity, a fact which seems to explain the high incidence of ADHD in this patient group. The magnitude, of the problem is increasing with the increased survival rate among premature infants.

Association of the dopamine transporter (DAT1) 10/10-repeat genotype with ADHD symptoms and response inhibition in a general population sample

“…However, if part of the cognitive deficit associated with ADHD is due to nongenetic factors such as perinatal environmental influences, 51 then adjusting for IQ might remove some of this nongenetic effect in the ADHD group proportionally more than in the non-ADHD group. This may be especially important for selective attention.…”

“…49,50 We recognise that ADHD has multiple causes, both genetic and environmental. The contribution of the DAT1 gene as one of multiple genetic factors is the focus of this study, but we do not discount other genetic factors (such as the contribution of the DRD4 gene) or nongenetic factors, such as the effects of fetal distress on brain anatomy and function, as proposed by Lou 51 and others. These factors may differentially affect the various components of attention.…”

Environmental Risk Factors by Gender Associated With Attention-Deficit/Hyperactivity Disorder

“…[38][39][40][41] The mechanism of how tobacco smoke affects the fetal brain remains unclear, 6,33 but it has been hypothesized that perinatal events resulting in hypoxia may affect brain development and lead to ADHD. 11,42,43 Such risk factors include threatened abortion, threatened preterm labor, preeclampsia, prematurity, intrauterine growth retardation, low Apgar scores, and fetal distress. 35,44,45 Our study contradicts some of these findings in that we found no association with acute events around delivery except for the rare event of cord prolapse in girls, also suggested in a recent study.…”

Inibição da atividade da citrato sintase cerebral em um modelo animal de sepse

“…(50) Konarska et al (51) reported that regional deficits in the frontal lobe, particularly in the anterior cingulate and the orb to the frontal cortex, consistently delineate subjects with central nervous system disorders from the general population. We hypothesize that mitochondrial dysfunction may be related to CNS damage in sepsis.…”