Both ADHD (attention-deficit/hyperactivity disorder) and autism are neurodevelopmental neurotypes that often co-occur and share certain behavioral, biological, and neuropsychological characteristics (Antshel et al., 2013). However, there are also important differences between the two neurotypes.
Neurobiology
Neurobiologically, ADHD and autism share some common pathways, particularly involving the dopaminergic system (DS) (Mariggiò et al., 2021). However, neuroimaging studies have also identified differences in functional connectivity between ADHD and autism. In ADHD, there is evidence of hypoactivation in brain networks involved in executive functions and attention, such as the frontoparietal network (Cortese et al., 2012). In contrast, autistic individuals show alterations in the intrinsic functional centrality of networks, particularly in temporolimbic areas (Martino et al., 2013). These differences in functional connectivity may contribute to the distinct clinical presentations and symptoms observed in ADHD and autism.
Studies have shown that individuals with ADHD exhibit atypical functionalities in brain regions involved in executive functions and attention, such as the frontoparietal network and the ventral attentional network. These atypical functionalities are thought to contribute to ADHD symptoms, including difficulties with attention, impulse control and executive functions (Cortese et al., 2012).
On the other hand, autistic individuals show atypical functionalities in brain regions involved in social cognition, such as temporolimbic areas, as well as in regions involved in sensory processing and integration. These atypical functionalities may underlie the social and communication difficulties, as well as sensory sensitivities, observed in individuals with autism (Martino et al., 2013).
Genetic factors
Genetic factors also play a role in both ADHD and autism. Family and twin studies have provided support for the hypothesis that ADHD and autism originate in partly similar familial/genetic factors. However, specific genetic markers and loci associated with the simultaneous occurrence of ADHD and autism are still under investigation (Rommelse et al., 2010). Some studies have identified common genetic variants and pathways that are shared between ADHD and ASD, suggesting some overlap in the genetic architecture underlying the two neurotypes. However, there are also disorder-specific genetic factors that contribute to the unique characteristics of each disorder (Purper-Ouakil et al., 2011).
One study found that SHANK2 could be considered a potential pleiotropic gene underlying the genetic overlap between ADHD and autism (Ma et al., 2021).
Another study found that single nucleotide polymorphisms (SNPs) of the dopamine receptors DRD1 and DRD2 could be considered potential risk factors for both autism and ADHD. However, only DRD2-12 (rs7131465) was significantly associated with a higher risk for autism/ADHD overlap (Lau-Zhu et al., 2019). This suggests that although both neurotypes may share common neurobiological pathways involving DS, there are distinct genetic factors that contribute to the development of each condition.
Symptoms
Regarding reaction time variability, a meta-analysis found that it is increased in autism only when children with comorbid ADHD are included in the sample (Karalunas et al., 2014). This suggests that the increased reaction time variability observed in autism may be due to the presence of ADHD symptoms rather than being specific to autism.
Another study found that attentional difficulties associated with ADHD may be related to an increased cost of shifting attention, which could contribute to the overlap in symptoms observed in both individuals with autism and ADHD (Gargaro et al., 2017). However, the specific neural mechanisms underlying these attentional difficulties remain unclear.
From a neurobiological perspective, ADHD is characterized by an abnormal interaction between large-scale brain circuits, particularly those involved in attention, executive functions, and impulse control. Neuroimaging studies have shown that individuals with ADHD exhibit atypical functionality in brain regions such as the prefrontal cortex, basal ganglia and cerebellum (Cortese & Castellanos, 2012). These atypical functionalities are thought to contribute to ADHD symptoms, including inattention, hyperactivity and impulsivity.
Autism, on the other hand, is characterized by deficits in social interaction and communication, as well as restricted and repetitive behaviors and interests (Hollander et al., 1998). Neurobiological studies have identified atypical functionalities in brain regions involved in social cognition, such as the mirror neuron system, as well as in regions involved in sensory processing and integration (Saffin & Tohid, 2016). These atypical functionalities may underlie the social and communication difficulties, as well as sensory sensitivities, observed in individuals with autism.
While there is some overlap in the neurobiological underpinnings of ADHD and autism, there are also distinct differences. For example, studies have shown that people with autism have difficulties with language and executive functions such as planning and working memory. In contrast, people with ADHD may have deficits in attention and impulse control, but may not have the same level of difficulty with language and executive functions (Landa & Goldberg, 2005).
Neural correlates of theory of mind (ToM) or mentalizing difficulties are reported in both ADHD and autism, but the neural mechanisms underlying these common deficits are relatively unknown (Ilzarbe et al., 2020). Further research is needed to better understand the similarities and differences in the neural correlates of ToM in ADHD and autism.
Medications
Methylphenidate
The use of methylphenidate in autism has been a topic of interest in the literature. Several studies have investigated the effects of methylphenidate on symptoms associated with autism, particularly hyperactivity and inattention. It has been shown to increase brain activation in regions involved in inhibition and time discrimination. However, the effects of stimulant medications on brain function in people with autism are less clear and further research is needed to determine their effectiveness in this population (Rubia et al., 2014).
A systematic review and meta-analysis by Sturman et al. (2017) found that short-term use of methylphenidate could improve symptoms of hyperactivity and possibly inattention in children with autism who are tolerant to the medication. However, the low quality of evidence limits certainty about the magnitude of these effects. Another study by Posey et al (2005) reported that methylphenidate was often effective in treating hyperactivity associated with pervasive developmental disorders, although the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder. Adverse effects were more common.
In a randomised controlled trial (Jahromi et al., 2008), methylphenidate was found to have a significant positive effect on social communication and self-regulation in children with pervasive developmental disorder and hyperactivity. The study reported improvements in joint attention behaviors, response to joint attention demands, self-regulation, and regulated affective state.
However, it is important to note that the literature on the use of methylphenidate in autism is not entirely conclusive. Wong et al. (2015) conducted a comprehensive review of evidence-based practices for children and youth with autism and found that evidence for the use of pharmacological agents, including methylphenidate, in treating social and communication impairments in autism is lacking. Similarly, Babakr et al (2022) reported that although methylphenidate and clonidine have demonstrated efficacy in treating hyperactive symptoms associated with autism, there is no evidence that they effectively treat social or communication impairments.
In addition, the literature suggests that response to methylphenidate in people with autism may vary. In a study by (McCracken et al., 2013), it was found that methylphenidate response and tolerability in children with autism varies widely, and this variability may be influenced by monoaminergic gene variants. Similarly, Hara et al. (2015) reported that methylphenidate appeared to be less effective and have more adverse effects in patients with autism compared to children with typical ADHD.
Overall, the literature on methylphenidate use in autism suggests that it may have some beneficial effects on symptoms of hyperactivity and possibly inattention. However, the evidence is limited and of low quality and there is a lack of evidence supporting its effectiveness in treating social and communication impairments associated with autism. Future research should consider extending the duration of treatment and follow-up, and confirming the minimal clinically important difference in children with autism using validated outcome scales (Sturman et al., 2017).
Atomoxetine
The literature on the use of atomoxetine in autism is limited and inconclusive. Several studies have examined the efficacy and safety of atomoxetine in treating ADHD symptoms in people with autism, but results are mixed.
A systematic review and meta-analysis by Patra et al. (2019) found that atomoxetine may be effective in improving hyperactivity and inattention in children with autism spectrum disorder and ADHD. However, the review also noted that atomoxetine was associated with an increased risk of non-serious adverse effects such as nausea, vomiting, decreased sleep, and decreased appetite. Similarly, Ghanizadeh (2012) stated that there is speculation that children with severe symptoms of autism and ADHD taking atomoxetine may experience a higher rate of adverse effects.
Another systematic review and meta-analysis by Rodrigues et al. (2020) examined the efficacy and safety of atomoxetine in children with autism spectrum disorder and ADHD. The analysis of three randomized placebo-controlled trials found that atomoxetine was effective in relieving ADHD symptoms such as hyperactivity and inattention (Rodrigues et al., 2020). However, the quality of evidence for all interventions was low/very low (Rodrigues et al., 2020).
Ghanizadeh (2012) noted that there are insufficient controlled clinical trials to demonstrate the efficacy of atomoxetine for treating ADHD symptoms in autism. Evidence suggests potential efficacy of atomoxetine, but current evidence is inconclusive. In addition, the author stated that the results cannot be generalized to long-term administration of atomoxetine in autism.
It is worth noting that atomoxetine is primarily prescribed for ADHD, and approximately one-third of children and adolescents with autism also have ADHD (Patra et al., 2019). The use of atomoxetine in people with autism and ADHD is supported by some studies. For example, Howes et al. (2017) stated that atomoxetine, both alone and combined with psychosocial therapy, significantly reduced ADHD symptoms (Howes et al., 2017). Lord et al. (2020) also noted that methylphenidate, atomoxetine, and guanfacine are beneficial for ADHD symptoms in autism (Lord et al., 2020).
In conclusion, the literature on the use of atomoxetine in autism is limited and inconclusive. While some studies suggest potential efficacy of atomoxetine in improving ADHD symptoms in people with autism, the evidence is inconclusive and there are concerns about adverse effects. Further research, including controlled clinical trials, is needed to determine the efficacy and safety of atomoxetine in this population.
Summary
In summary, although ADHD and autism share some behavioral and neurobiological characteristics, there are also important differences between the two neurotypes. ADHD is characterised by difficulties with attention, executive functions and impulse control, while autism is characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours.
While ADHD and autism share some neurobiological pathways, particularly involving the dopaminergic system, there are differences in the specific genetic factors and neural mechanisms underlying the symptoms of each disorder. Further research is needed to better understand the complex interplay between these factors and how they contribute to the development and expression of ADHD and autism symptoms.
Genetic factors play a role in both neurotypes, but the specific genes and mechanisms involved are still under investigation. Treatment approaches, particularly the use of stimulant medication, may differ between ADHD and autism. Further research is needed to better understand the neurobiological underpinnings of these neurotypes and to develop more targeted and effective treatments.
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