Biopsychosocial Perspective On Adhd In Childhood Epilepsy

Introduction

Epilepsy is a brain disorder characterized by at least two unprovoked (or reflex) seizures occurring more than 24 hours apart or one unprovoked (or reflex) seizure and a probability of 60% for the occurrence of further seizures after two unprovoked ones (Fisher et al., 2014). Based on types of seizures onset, epilepsy can be classified as either as focal, generalized, or unknown. A specific epilepsy syndrome diagnosis is established with the incorporation of information on seizure type, EEG changes, and imaging findings (Fisher et al., 2017) (Scheffer et al., 2017). Epilepsy is relatively common among children and has a significant impact on their development, parents, and society (Mountz, Patterson & Mandeep, 2016).

Approximate prevalence rates between 3.2 and 5.1/1000 are reported for childhood epilepsy (Forsgren et al., 2005). The first year of life appears to be when the most incidents happen (Hauser, 1994). However specific seizure types, epilepsy syndromes incidence and prevalence in children are not as well documented as the incidence of epilepsy (Camfield & Camfield, 2015).

Besides being characterized by its core features, pediatric epilepsy may also involve mental health problems, including learning disabilities, disease-related quality of life impairments and psychopathology. The most frequent neuropsychiatric disorder among children with epilepsy is ADHD. It has been estimated that among children with epilepsy, 30% of them may meet criteria for ADHD (Besag et al. 2016) (Cohen et al., 2013) (Torres et al., 2008). ADHD is one of the most prevalent childhood neurodevelopmental disorders. It is defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) as a neurodevelopmental disorder characterized by a minimum of six out of nine listed symptoms of inattention and/or a minimum of six out of nine listed symptoms of hyperactivity and impulsivity. These symptoms must be atypical for the developmental stage, be present for at least 6 months, be severe enough to interfere with functioning, occur in at least two settings (i.e home and school), and have an age of original onset of less than 12 years.

This disorder can be classified based on type and severity scale. Types of ADHD include predominately inattentive-, predominately hyperactive/impulsive-, or combined-type presentations, and they can be mild, moderate or severe (American Psychiatric Association. DSM-5 Task Force. Diagnostic and statistical manual of mental disorders DSM-5. 5th ed. Washington, DC: American Psychiatric Association; 2013.). The inattentive ADHD subtype has been found to be more dominant compared to the other subtypes, with a percentage of 24 to 52% in children with comorbid diagnoses (Williams et al., 2016).

Models attempting to explain the development and impact of ADHD and epilepsy in children have been proposed. However, these models explore them separetely. They represent an integrative approach incorporating illness-related variables and psychosocial factors, trying to shift the primary focus from biological predictors towards psychosocial ones (Elliott & Richardson, 2014) (Schoenfelder & Kollins, 2016). There is strong evidence that the full biopsychosocial model explains a significantly larger amount of variance in quality of life of children with epilepsy compared with the biological-biomedical model alone. When the individual domains of the biopsychosocial model were controlled for, the psychological and social domains still explained a greater amount of the variance in quality of life compared with the biological–biomedical model (Elliot & Richardson, 2014).

Therefore, when trying to understand the development of ADHD in children with epilepsy more in depth a biopsychosocial perspective is suggested. The biopsychosocial model suggests that the explanation for medical conditions is multifaceted. Health quality is considered as a result of the interaction between biological, psychological and social factors. Furthermore, from a biopsychosocial perspective in order to gain a better understanding of life quality a person’s lived experience needs to be incorporated.

The aim of this essay is to explore the relationship between ADHD and epilepsy from a biopsychosocial perspective. It reviews recent research investigating possible biological and psychosocial factors explaining the relationship between these two disorders.

Biological factors

The pathophysiological mechanism of epilepsy and its psychiatric comorbidity is complex. Several hypotheses were investigated to explain the association between epilepsy and ADHD either in human or in animal models. These investigations failed to identify a cause, however interacting mechanisms were suggested (LaFrance, Kanner, & Hermann, 2008). The following mechanisms were linked with both ADHD and childhood epilepsy:underlying brain pathology, disturbed neuronal signaling, repeated seizures, epileptic electroencephalography discharge, and environmental and genetic predispositions(Williams, Giust, Kronenberger, & Dunn, 2016).

There is emerging evidence suggesting a potential role of oxidation stress in the pathogenesis of many psychological disorders including ADHD. There is a linear association between elevated oxidative stress level and the increased risk of ADHD (Kul et al., 2015). Exposure to oxidative stress impairs the structure and functions of neuronal receptors and alters the neurotransmission of dopamine and serotonin (Popa-Wagner, Mitran, Sivanesan, Chang, & Buga, 2013). Reactive oxygen species induce lipid peroxidation that alters membrane excitability and decreases the cell membrane binding affinity to dopamine, which is thought to be deficient in striatofrontal circuits and leads to the increase in susceptibility to ADHD (Joseph, Zhang-James, Perl, & Faraone, 2015). Frequent seizure activity increases the production of free radicals in the brain in patients with epilepsy, which puts them at a higher risk for psychological and cognitive disorders (Mare_s, Stopka, Nohejlov_a, & Rokyta, 2013). Elhady et al. (2018) demonstrated a significant association between oxidation stress assessed by increased MDA serum level and epilepsy especially in those who developed ADHD.

These findings suggest that uncontrolled seizure could be the link between oxidation stresses and increased the susceptibility for ADHD in children with epilepsy. The fore-mentioned mechanisms attempt to give an explanation for the association between ADHD and childhood epilepsy, however they do not explain why some people are more prone to these disorders.

In their review investigating epilepsy/ADHD phenotype Lo-Castro & Curatolo (2013) made a summary of the majority of candidate genes. These genes are involved in synaptic formation/remodeling/maintenance (NRX1, CNTN4, DCLK2, CNTNAP2, TRIM32, ASTN2, CTNTN5, SYN1), neurotransmission (SYNGAP1, GABRG1, CHRNA7), or DNA methylation/chromatin remodeling (MBD5).

Neuropsychological

Attentional problems thought to be caused by epilepsy were summarized in a review of epilepsy and ADHD in 2016: multiples studies showed a higher level of impact on complex attention compared to simple attention; significant difficulties in the areas of working memory and processing speed are present in children with epilepsy; epiliptic activity has an impact on sustained, selective, and divided attention types (Williams et al., 2016). In addition to cases where epilepsy in children is directly causing attentional problems, children with epilepsy who manifested ADHD symptoms not caused by it were identified. In children with new onset seizure, one study has shown a likelihood of 2.5 of already carrying an ADHD diagnosis at time of presentation compared to controls having ADHD without seizures. (Hesdorffer DC, Ludvigsson P, Olafsson E, et al. ADHD as a risk factor for incident unprovoked seizures and epilepsy in children. ArchGen Psychiatry. 2004;61:731–736.)

An association between ADHD-type symptoms and epilepsy has also been suggested by animal studies. In a study where epilepsy was induced in male Wistar rats, half of them exhibited chronic ADHD-like abnormalities. In particular, they showed attention deficits and increased levels of impulsivity. These impairments correlated with the suppressed noradrenergic transmission in locus coeruleus outputs (Pineda et al. 2014).

Another rat study examined the impact of interictal discharges in cognition by developing a model of frequent focal interictal spikes (IIS). Short term plasticity (STP) and behavioral outcomes were studied in adulthood. The results showed that frequent focal interictal spikes are associated with a significant increase in short-term plasticity (STP) bilaterally in the prefrontal cortex (PFC). IIS rats showed marked inattentiveness without significant transformations in motivation, anxiety or hyperactivity. It was concluded that GABAergic blockade during early-life and focal IIS in the PFC disrupt neural networks and are associated with long-term consequences for behavior at a time when ISS are no longer present. It can therefore be assumed that these findings might have important implications for ADHD associated with childhood epilepsy (Hernan et al., 2014).

Social aspects

Oostrom et al.,(2002) compared problems of attention in school children with newly diagnosed idiopathic or cryptogenic epilepsy with those in healthy classmates. They concluded that decreased attentional efficiency was related to prior school and behavior difficulties and a maladaptive reaction to the onset of epilepsy rather than the epilepsy variables themselves.