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Do "ACEs" Influence ADHD Development in Youth? Genetic and Neuroanatomy Factors Explored.

Updated: Mar 31

Dive into groundbreaking research by student, Gershon Ungar, who's in a Physician Assistant course at Touro University. Explore the intricate interplay of Adverse Childhood Experiences (ACEs), genetics, and neuroanatomy in the development of Attention-Deficit/Hyperactivity Disorder (ADHD). Gain insights into associated psychological, behavioral, and neurological outcomes, shedding light on crucial factors shaping the trajectory of ADHD in children and young adults. Uncover the intersection of nature and nurture in this compelling study that paves the way for a deeper understanding of ADHD etiology.


 

In Children and Young Adults, Does Exposure to Adverse Childhood Experiences (ACEs) Compared to Genetics and Neuroanatomy Affect the Development of

Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Psychological, Behavioral, and Neurological outcomes?


Executive summary


This paper highlights the prevalence of Adverse Childhood Experiences (ACEs) and their impact on mental health and its associated diseases, specifically Attention-Deficit/Hyperactivity Disorder (ADHD) and seeks to prove that ACEs have a much more significant impact on mental health conditions than previously realized. It also portends that the current narrow diagnostic categories do not fully capture the complexity and diversity of mental health disorders. The paper also questions the overreliance on psychotropic medications, particularly stimulants such as amphetamines for the treatment of ADHD. Instead, alternative treatments such as antidepressants are suggested as a viable option for ADHD treatment. The paper also examines the detachment of psychology from psychiatry, emphasizing the need for a holistic approach that considers biological, psychological, and social factors. Ultimately, the paper seeks to imbue a paradigm shift in mental health research and treatment, away from a reductionist and biomedical approach and towards a more integrative and patient-centered approach with specific focus on the source of the disorders, namely, ACEs.


Introduction


Attention-deficit/hyperactivity disorder (ADHD) and other psychological, behavioral, and neurological disorders have long been attributed to genetic and neuroanatomic factors (Farone et al. 2005; Haberstick et al. 2007; Heiser et al. 2006; McLoughlin et al. 2007; Amico et al. 2011; Xia et al. 2012; Seidman et al. 2011). However, recent studies have challenged this assumption, pointing instead to the significant impact of adverse childhood experiences (ACEs) on the development of these conditions (Maguire et al. 2015; Walker et al. 2021; Crouch et al. 2021; Brown et al. 2017; Hughes et al. 2017; Heim et al. 2010; Dube et al., 2003). ACEs are defined as a range of traumatic experiences that occur before the age of 18, including physical, sexual, or emotional abuse, neglect, and household dysfunction, among others (Felitti et al. 1998). ACEs are a common and widespread issue that affects a significant proportion of the population, with estimates suggesting that nearly two thirds of the United States population have experienced at least one ACE (Centers for Disease Control and Prevention, 2022).

Research has shown that individuals who experience ACEs are at a higher risk of developing ADHD and other psychological, behavioral, and neurological conditions (Maguire et al. 2015; Walker et al. 2021; Crouch et al. 2021; Brown et al. 2017; Hughes et al. 2017; Heim et al. 2010; Dube et al., 2003). Given the evidence, it is becoming increasingly clear that ACEs are a significant risk factor for the development of ADHD and other psychological, behavioral, and neurological conditions. Therefore, understanding the relationship between ACEs and these conditions is essential in developing effective prevention and intervention strategies. This literature review aims to explore the existing research on the link between ACEs and the development of ADHD and associated outcomes in children and young adults. By doing so, this paper will provide evidence to support the hypothesis that the cause of ADHD and related conditions is not primarily due to genetics, but rather to the impact of ACEs and as a result research should be focused on ACEs and how to prevent them and treat their outcomes.


Attention Deficit Hyperactivity Disorder, anxiety, and depression - are they genetic? Background on ADHD


Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects both children and adults. It is characterized by symptoms such as inattention, hyperactivity, and impulsivity, which can have a significant impact on daily functioning and social relationships. According to recent studies, the prevalence of ADHD in children and adolescents ranges from 7.2% to 15.5%, and the disorder affects boys more frequently than girls. Symptoms of ADHD most often persist into adulthood. (Wolraich et al. 2019).


Diagnosis of ADHD typically involves a comprehensive evaluation that includes a clinical interview, medical history, and assessment of symptoms. There are three subtypes of ADHD: predominantly inattentive, predominantly hyperactive/impulsive, and combined type (American Psychiatric Association 2022). Treatment options for ADHD include medication, behavioral therapy, and a combination of both. Stimulant medications, such as Ritalin and amphetamines, are commonly prescribed to manage symptoms of ADHD. Behavioral therapy may include parent training, social skills training, and cognitive-behavioral therapy. The effectiveness of treatment varies among individuals, and a combination of medication and behavioral therapy may be necessary for some individuals to manage their symptoms (Wolraich et al. 2019).


Previous research on the genetic basis of ADHD


Previous research has suggested a strong genetic basis for ADHD, with some studies finding risk increases of twofold to eightfold in family members of affected children (Faraone and Doyle 2001). Throughout the years, there have been numerous twin studies that demonstrated the heritability of ADHD with reported estimates of heritability between 60% and nearly 100%! (Farone et al. 2005; Haberstick et al. 2007; Heiser et al. 2006; McLoughlin et al. 2007). Although it’s worth noting, researchers so far have had little luck in identifying the actual genes that cause ADHD (Franke et al. 2009). Since finding the genes associated with ADHD has so far been elusive, some studies suggest that future research should focus on a different patient population such as patients with a comorbidity with other disorders when selecting subjects for genetic studies (Faraone et al., 2000).


Previous research on the neuroanatomic basis of ADHD


Previous research on the neuroanatomic basis of ADHD has highlighted several brain regions and neural pathways that may contribute to the disorder, however, the findings are confusing at best and inconsistent at worst. For example one study concluded that individuals with ADHD had a decrease in gray matter volume in the right and left anterior cingulate cortex (Amico et al. 2011). Another study concluded that there was “significant regional atrophy in the left thalamus in children with ADHD compared to controls'' (Xia et al. 2012). Yet another study concluded that individuals with ADHD had gray matter volume reductions in the caudate, frontal lobe, hippocampus, temporal cortex, and the occipital cortex, while the dorsolateral prefrontal cortex and the inferior parietal lobule were significantly larger (Seidman et al. 2011). Another study found that individuals with ADHD had increases in gray matter volume in the precentral gyrus and the supplementary motor area (Sutcubasi Kaya et al. 2016). Rubia et al. (2009) concluded that individuals with ADHD “showed reduced activation and functional inter-connectivity in bilateral fronto-striato-parieto-cerebellar networks”. Cortese et al (2012) concluded that individuals with ADHD demonstrated hypoactivation of the frontoparietal network and ventral attentional network while demonstrating hyperactivation of the default, ventral attention, and somatomotor networks. Rubia, K. (2018) concluded that individuals with ADHD showed reduced activation of the right inferior prefrontal cortex, putamen, and the globus pallidus in the left inferior frontal gyrus. All in all, if one were to read these studies without having met someone with ADHD, one would assume that those who have ADHD would experience much more severe impaired functioning.


Need for a reevaluation of the causes of ADHD


While previous research has predominantly focused on the genetic and neuroanatomical bases of ADHD, there is growing evidence that adverse childhood experiences (ACEs) and past traumas may also contribute to the development of the disorder. ACEs, such as abuse, neglect, and household dysfunction, have been shown to be significantly associated with increased risk of ADHD (Jimenez et al., 2017). Moreover, a recent meta-analysis of 700 adolescents and young adults, found that childhood trauma is associated with altered brain structure and function in areas that are implicated in ADHD (van der Meer et al., 2019). Despite this evidence, the role of ACEs and past traumas in the etiology of ADHD is still under-appreciated and under-researched. Therefore, there is a pressing need for a reevaluation of the causes of ADHD, with a greater emphasis on the potential contribution of ACEs and past traumas. Such an approach may not

In Children and Young Adults, Does Exposure to Adverse Childhood Experiences (ACEs) Compared to Genetics and Neuroanatomy Affect the Development of

Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Psychological, Behavioral, and Neurological outcomes? 8 only improve our understanding of the disorder but also inform the development of more effective prevention and intervention strategies for individuals affected by ADHD.


Adverse Childhood Experiences (ACEs)

Definition of ACEs


Adverse Childhood Experiences (ACEs) are a collection of traumatic and stressful experiences that occur during childhood, including physical, sexual, or emotional abuse; neglect; household dysfunction such as domestic violence, substance abuse, mental illness, divorce, or incarceration of a household member; and community violence. These experiences can have profound and lasting effects on physical, emotional, and cognitive development, and can increase the risk of developing a range of negative health outcomes throughout the lifespan, including mental health disorders. The concept of ACEs was first introduced by a landmark study by Felitti et al. (1998) which examined the relationship between childhood abuse and household dysfunction and a range of negative health outcomes in adulthood. Since then, a growing body of research has established the significant and long-lasting effects of ACEs on health and wellbeing. Understanding the impact of ACEs on ADHD and related disorders is a critical component of developing effective prevention and intervention strategies.


Types of ACEs


Adverse childhood experiences (ACEs) are a range of traumatic events that can occur during childhood and adolescence. There are different types of ACEs that have been identified in research. Felitti et al. identified seven categories of ACEs, including psychological, physical, sexual, and substance abuse, as well as mental illness in the household, mother being treated violently, and criminal behavior at home (Felitti et al., 1998). The study used a retrospective cohort design and surveyed more than 17,000 patients who were part of a large health maintenance organization in California. Participants completed a confidential survey that asked about their experiences of seven different categories of ACEs. The data was then analyzed to assess the prevalence and cumulative effects of ACEs on a range of health outcomes, including mental health, physical health, and health risk behaviors. The study found a strong association between the number of ACEs experienced and a range of negative health outcomes. This study was conducted in two waves, and during the second wave of the study a few more categories were added including psychological and physical neglect. Other researchers have added to this list, including peer victimization, particularly in the form of bullying, which can be a lot more prevalent than child abuse and neglect and according to some researchers accounts for an over 50% increase in risk of adverse outcomes (Arseneault 2017, Jackson et al. 2016, Wade et al. 2014). Recognizing and addressing ACEs can be a crucial step in preventing and treating mental health issues in children and adolescents.


Prevalence of ACEs in the general population


Adverse childhood experiences (ACEs) are a common occurrence in the general population, with a significant proportion of individuals reporting at least one ACE. According to a national survey conducted in the United States, nearly two-thirds of adults (61%) reported experiencing at least one ACE, with nearly 16% reporting four or more ACEs (Centers for Disease Control and Prevention, 2022). A study conducted in eight Eastern European countries reported similar findings, with more than half of the individuals reporting at least one ACE and approximately 14% reporting three or more ACEs (Bellis et al. 2014). The prevalence of ACEs varies by demographic factors, with individuals from low-income and minority backgrounds, especially women, being more likely to experience ACEs (Centers for Disease Control and Prevention 2022, Bellis et al. 2014). In addition, the prevalence of ACEs is higher among individuals with mental health and substance abuse problems, highlighting the need for early intervention and prevention efforts (Felitti et al., 1998, Bellis et al. 2014).


ADHD and ACEs

The relationship between ACEs and ADHD

Research has consistently shown a significant relationship between ACEs and an increased risk for developing ADHD in childhood and adolescence. A systematic review by Maguire et al. (2015) which reviewed 30 studies, concluded that there was a clear cause and

effect between emotional abuse and neglect and ADHD symptomatology. It’s worth noting that the study also differentiated between children with externalizing features, such as aggressive, destructive, impulsive, and ADHD like behaviors, and internalizing features, such as being withdrawn, somatic complaints, and depression/anxiety. While the majority of studies found externalizing features to be predominant, others found internalizing features just as common in children facing ACEs. It’s also interesting to note that some of the symptoms of ADHD and some of the symptoms of Generalized Anxiety Disorder and Major Depressive Disorder (which the previous study categorized as externalizing vs internalizing features), significantly overlap - particularly restlessness and difficulty concentrating which are primary features of all three (American Psychiatric Association. 2022). Furthermore, a systematic review by Zhang et al. (2022) which reviewed 70 studies, revealed that ACEs were associated with a significantly increased risk of ADHD diagnosis. A study which reviewed nationally representative samples of over 40,000 parents from the National Survey of Children’s Health, found a two to threefold increase in the prevalence of ADHD amongst children who experienced ACEs vs those who didn’t (Walker et al. 2021). Similar studies of the same magnitude revealed the same results (Crouch et al. 2021. Brown et al. 2017). Overall, these findings emphasize the importance of understanding the impact of childhood trauma and adversity on mental health outcomes, including the development and manifestation of ADHD.


The relationship between ACEs and other disorders, including depression, anxiety, and substance abuse


Adverse Childhood Experiences (ACEs) are not only associated with an increased risk of ADHD, but also with a range of other disorders, including depression, anxiety, substance abuse, and PTSD. A meta-analysis of 37 studies found that individuals with ACEs were at higher risk for developing depression, with a dose-response relationship between the number of ACEs and the likelihood of depression (Hughes et al. 2017). Similarly, a systematic review of 26 studies found a strong association between ACEs and anxiety disorders, including generalized anxiety disorder, social anxiety disorder, and panic disorder, as well as a host of other mental disorders including unipolar depression, bipolar disorder, post-traumatic stress disorder, schizophrenia, eating disorders, and personality disorders (Heim et al. 2010). Another longitudinal study of over 17,000 individuals found that those with four or more ACEs had a 4- to 12-fold increased risk of developing substance abuse disorders (Dube et al., 2003). Once again, it’s interesting to note the common denominator of these mental disorders, namely, ACEs. Furthermore, as mentioned earlier, many of these disorders share extremely similar and overlapping symptomatology yet are characterized as distinct disorders and treated symptomatically i.e. anxiolytics for anxiety, antidepressants for depression, stimulants for ADHD etc. Could it be that conventional science is focusing too much on the symptoms and too little on the root cause and how to fix it? Furthermore, if ACEs (which, yet again, is currently characterized by very specific incidents and doesn’t consider hundreds of other potential traumatic childhood experiences both conscious and

In Children and Young Adults, Does Exposure to Adverse Childhood Experiences (ACEs) Compared to Genetics and Neuroanatomy Affect the Development of

Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Psychological, Behavioral, and Neurological outcomes? 13 subconscious) are indeed the root cause of many of the DSM V - TR disorders, future research must focus on identifying why certain people develop specific symptoms/disorders due to ACEs while others develop different symptoms/disorders.


ADHD. The lone wolf?


As mentioned previously, the symptoms of ADHD and anxiety significantly overlap. In addition to the restlessness and difficulty concentrating which are primary features of both (American Psychiatric Association. 2022), there also seems to be an overlap with sleep disturbances (Wajszilber et al. 2018, Chellappa et al. 2022), intrusive thoughts (Abramovitch et al. 2009), and GI disorders (Kedem et al. 2020). That being said, ADHD has somehow been singled out from the cluster of anxiety/depression like disorders and is treated with a completely different class of drugs, namely, amphetamines. What's even more confounding is that in a meta-analysis which reviewed 133 double-blind randomized controlled trials of over 11,000 children and 5,000 adults, it was found that bupropion (an antidepressant) was significantly more effective in treating ADHD in children and adolescents than methylphenidate (as rated by clinicians). Yet the researchers still conclude that methylphenidate is the best treatment option (Cortese et al. 2018). Furthermore, there has been a substantial increase in the diagnosis of ADHD and subsequent amphetamine prescription in children. In 2011 that number of children diagnosed with ADHD was at 11% and it just keeps on rising. ADHD is the second most common diagnosis in children after obesity (Ahmed et al. 2017). Even more disconcerting is that a recent study found that in schools with the highest rates of stimulant therapy for students with ADHD, students without ADHD had 36% increased odds of abusing the drug (McCabe et al. 2023). In a study of 81 college students with ADHD, more than 60% admitted to giving away their medication to students without prescriptions (Arria & DuPont, 2010)! In a study among surgeons, 8.9% of surgeons admitted to either medical or nonmedical stimulant use, but when they were guaranteed anonymity that number rose to close to 20% (Leon et al., 2018). Considering its high potential for abuse, these numbers are shocking. Perhaps if more focus would be placed on identifying the common sources of these disorders (ACEs), as well as the commonalities these disorders share, research would then be able to focus on targeting the source as well as finding unified treatments and psychotherapeutic models to heal these people.


Conclusion


While there seems to be an avalanche of research over the past few decades on the horrendous effects of ACEs, very little, if any, research has been dedicated to understanding the relationship between ACEs and its associated psychopathology. While science has made great strides in studying observable phenomena, such as the impact of ACEs on the brain, as well as the actual effects of ACEs in terms of DSM V-TR diagnoses, understanding how or why this effect takes place has evaded research. Given that these associations are likely internal experiences that cannot be directly observed or measured, it is understandable why research in this field can be challenging. Furthermore, as previously noted, since ACEs produce a plethora of symptoms characterized sometimes as internalizing and externalizing features (Maguire et al. 2015), and since none of these symptoms/features by themselves are characterized as “disorders,” what good would research do in associating these features with an ACE? Instead research is hyper focused on finding the ACE, finding the “disorder” (DSM V diagnosis), and establishing a connection. This problem is not only apparent with ACEs and its effects, but is a rather general problem across all of psychiatry. Most of the current literature accepts the current DSM V list of mental illness’ as fact, just like it accepts physical diseases as fact. It is then up to the researcher to find and uncover etiologies, pathophysiology’s, and treatments for these diseases. For instance: There are no studies on the effects of ACEs on workaholism or procrastination - for neither is a disease or diagnosis. It is, however, safe to assume that workaholism and procrastination are not the best of habits, to say the least, and presumably carry negative consequences. Moreover, there aren’t even studies linking ACEs with restlessness and/or lack of concentration, which are the fundamental symptoms of anxiety, ADHD, and depression - but aren’t standalone diagnoses. Furthermore, even if a study were to establish a connection - how that connection is made would still remain an unanswered question. Moreover, while psychologists did propose many theories on the psychological connection between ACEs and its consequences, like Beck’s Cognitive Theory (Clark et al. 1999), which theorizes that depressed people have negative and hopeless thoughts or core beliefs about themselves, which are usually developed during childhood, this too is (A) limited to the existing disorders/diseases as defined by the DSM and (B) is largely disregarded by the medical community who favor tangible and objective theories on the nature of mental illness. After all, it’s hard to detect negative core beliefs on an fMRI machine. The problem with this approach in mental illness is that many of the symptoms and etiologies overlap (Brown et al. 2001; Kessler et al. 1998). One study of over 1100 people found that between 55% - 75% of patients with an anxiety or mood disorder had at least one additional anxiety or depressive disorder at the time of assessment (Brown et al. 2001). Additionally, the human mind and psyche is more complex and less observable than human anatomy and pathophysiology. Indeed, in recent years some researchers have called for a Unified Treatment for Emotional Disorders. Barlow et al. (2004) suggests one unified approach to emotional disorders which would include three components: “(a) altering antecedent cognitive reappraisals; (b) preventing emotional avoidance; and (c) facilitating action tendencies not associated with the emotion that is dysregulated.” One of the reasons behind this change in approach, as the paper so adequately explains:

There is wide agreement that DSM-IV represents the zenith of a "splitting approach" to nosology, with the obtained advantage of high rates of diagnostic reliability. But, there is growing suspicion that this achievement has come at the expense of diagnostic validity, and that the current system, as suggested above, may be erroneously distinguishing categories that are minor variations of broader underlying syndromes. (p. 211)

Barlow et al. indeed wrote and implemented the protocols for a Unified Treatment approach and the results were rather promising. Eighty five precent of the patients were classified as “treatment responders” (Ellard et al. 2010). Furthermore, in a RCT of 223 participants, a

randomized group of participants with multiple diagnoses were divided in two groups. One group was treated with the Unified Treatment Protocol and the other with single-disorder protocols. The study results were that the Unified Treatment Protocol produced the same results as single-disorder protocols but with less attrition as well as the fact that it treated a multitude of disorders and not just one (Barlow et al. 2017). While this is not to suggest that Barlow’s protocol is the ultimate and only answer to all mental health disorders, it does stress the importance of deconstructing these disorders as we know them which would allow further research to both: understand the causal relationship between the symptom and its instigator (namely, ACEs), and find better treatment modalities that can focus on treating the symptom as a symptom and ultimately treating the root cause.


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