Table 1.
Main features shared that suggest a parallelism between ADHD (Attention deficit/hyperactivity disorder) and FASD (Fetal alcohol spectrum disorders).
| FASD (PAE) | ADHD | |
|---|---|---|
| NEUROLOGICAL ALTERATIONS | ||
| Cognitive and behavioral deficits | Delay in learning and memory (Hellemans et al., 2010) | Deficits in learning, cognition (attention), and behavior (hyperactivity/Fmpulsivity) (Casey et al., 2007; Albrecht et al., 2015) |
| Ongoing pattern of inattention and/or hyperactivity impulsivity | Children with FASD often present with attentional problems similar to those observed with ADHD (Coles et al., 1997; Mick et al., 2002; Jacobson et al., 2011) | |
| Prospective memory | PAE was related to ADHD, but ADHD was not related to prospective memory performance (Lewis et al., 2016) | |
| Physiological abnormalities | Affects different stages of brain development from neurogenesis to myelination (Riley et al., 2011; Reynolds et al., 2011), which leads into behavioral and cognitive deficits during youth and adulthood | Children show a core deficit in behavioral inhibition, leading to impairments in working memory, self-regulation, internalization of speech and reconstitution (Barkley, 1997) |
| HYPOTHALAMIC-PITUITARY-ADRENAL AXIS (HPA) | ||
| Disfunction of HPA axis | Alterations in the activity and regulation of HPA and HPG axis (Handa et al., 1985; Lee and Rivier, 1996; Weinberg et al., 2008; Comeau et al., 2015) | Involvement of HPA axis has been clinically described in children with ADHD (Kaneko et al., 1993; Hastings et al., 2009) |
| Altered responsivity to stressors | Increasing sensitivity to stressors and vulnerability to stress-related disorders (Lee et al., 2000; reviewed in Hellemans et al., 2010) | An impaired response to stress has been suggested as a marker to the more developmentally persistent form of ADHD (King et al., 1998; Snoek et al., 2004; Pesonen et al., 2011; reviewed in Johnson, 2015) |
| KEY NEUROTRANSMITTER SYSTEMS AFFECTED | ||
| Dopaminergic system | Prefrontal cortex is particularly affected by PAE, mainly dopamine system (Juh et al., 2005; Smith et al., 2012; Kim et al., 2013; Uban et al., 2015) | Daergic system is affected (Curatolo et al., 2010). Prefrontal cortex is the region most affected (in regulating behavior and attention) via dopamine transmission (Arnsten, 2007) |
| DA transporter system (DAT) | PAE direct regulates DAT function by altering endosomal recycling of the transporter (Methner and Mayfield, 2010); PAE decreases DAT binding sites in brain (Druse et al., 1990; Szot et al., 1999): in contrast, in adult rats, ethanol increases the number of DAT binding sites in brain (Jiao et al., 2006) | DAT is involved in ADHD and/or its treatment (reviewed in Mazei-Robinson and Blakely, 2006); High striatal DAT availability in most adults with ADHD (reviewed in Krause et al., 2006) |
| DA receptors | PAE differentially affects regional expression of DA receptor subtypes (Flores et al., 2011). PAE males exhibited increased dopamine receptor expression in medial prefrontal cortex (Uban et al., 2015) | Polymorphisms of D4 and D5 receptors show a predisposition to develop ADHD (Kustanovich et al., 2004) |
| Cholinergic system | PAE may disrupt learning and memory in adolescence via a cholinergic mechanism (Perkins et al., 2015); Perinatal choline supplementation may attenuate alcohol-related behavioral changes (Monk et al., 2012) | Involved in ADHD cognitive dysfunction (Potter et al., 2006; Sarter and Paolone, 2011) |
| Glutamatergic system | PAE reduces NMDA receptor subunits expression (Rema and Ebner, 1999; Samudio-Ruiz et al., 2010; Bird et al., 2015) | Dysregulation of the NMDA receptors has been involved in ADHD (Chang et al., 2014) |
| Gabaergic system | PAE attenuates Gabaergic inhibition in amigdala, leading to hyperexcitability and anxiety (Zhou et al., 2010; Baculis et al., 2015); reduces Gabaergic neurons in vermis (Nirgudkar et al., 2016) and in cortex (Smiley et al., 2015); and affects cortical Gabaergic neuron migration (Skorput and Yeh, 2016) | Disturbed Gabaergic transmission in hippocampus (Sterley et al., 2016) and in prefrontal cortex (Tzanoulinou et al., 2016) have been involved in ADHD neuropathophysiology. GABAergic inhibitory neurons play a role in the neurobiology of ADHD (Nagamitsu et al., 2015). GAD1 polymorphysm is associated with ADHD (Bruxel et al., 2016) |
| CELLULAR FUNCTION | ||
| Altered gene expression | Down-regulation of 25 genes involved in cell proliferation, differentiation, and apoptosis, none were up-regulated (Hard et al., 2005); down-regulation of 104 genes involved in protein synthesis, mRNA splicing, and chromatin organization, none were up-regulated (Rogic et al., 2016) | Genome wide analysis in human ADHD individuals confirms the complexity and heterogeneity of ADHD etiology (Zayats et al., 2015). Down-regulation of 54 genes and up-regulation of 52 genes related with transcription, synaptic transmission, neurological system process and immune response in animal model of ADHD (De la Peña et al., 2015) |
| Oxidative stress (OS) | Altered gene expression in OS pathways in the adult hippocampus suggests a novel involvement of OS mechanisms in FASD (Chater-Diehl et al., 2016); PAE dysregulates OS in rats (Brocardo et al., 2012), and in Drosophila (Logan-Garbisch et al., 2014) | OS is increased in children with ADHD (Sezen et al., 2016); ADHD patients present an insufficient response to OS leading to damage (Joseph et al., 2015); Interventions with antioxidant represent potential options for the treatment of ADHD (Lopresti, 2015) |
| Growth factor signaling disruption | PAE in mice alters NGF and BDNF in brain (Ceccanti et al., 2016) | Higher levels of serum NGF in drug-naive ADHD patients (Guney et al., 2014); disrupting of BDNF signals found in children with ADHD (Liu et al., 2015) |
| EPIGENETICAL MODULATION OF GENE EXPRESSION | ||
| DNA methylation | Alterated DNA methylation program during neurulation (Zhou et al., 2011; and the genomic methylation profiles (Liu et al., 2009). Induced a decreased expression of methyl-binding protein MeCP2 in prefrontal cortex and striatum (Kim et al., 2013) | DNA methylation variation in genes related to neurodevelopmental and peroxisomal processes (Walton et al., 2016); Cytosine methylation (Mill and Petronis, 2008); Several genes methylated: DAT1 (Ding et al., 2016); IGF2 (Rijlaarsdam et al., 2016); 5-HT3A R (Perroud et al., 2016); SLC6A4 (Park et al., 2015) |
| chromatin configuration | Down-regulation of 104 genes involved in protein synthesis, mRNA splicing, and chromatin organization (Rogic et al., 2016) | Histone modification in ADHD (Mill and Petronis, 2008); histone acetylation increased significantly in the hippocampus by chronic lead exposure, causing ADHD-like symptoms (Luo et al., 2014) |
| microRNA | PAE is associated with dysregulation of several miRNA levels (Balaraman et al., 2013; Gardiner et al., 2016) | Small interfering RNA (siRNA) is involved in ADHD (Mill and Petronis; (Kandemir et al., 2014)); abnormal miRNA function contributes to ADHD (Wu et al., 2015; Garcia-Martínez et al., 2016; Ye et al., 2016) |