Deep and Debilitating Wounds: Neuropsychiatric Disease Among Traumatized Children

Dr. Drew W. Edwards, EdD, MS and Dr. Sean C. Orr, MD

Neuropsychiatric

Emotional Trauma and Adverse Childhood Events (ACEs) are robust risk factors for adolescent and adult neuropsychiatric disorders. Childhood adversity includes neglect, attachment disorder, physical and emotional trauma, and sexual abuse. Recently, investigators at Dell Medical School at the University of Texas in Austin demonstrated that childhood adversity and maltreatment are, “by far the most reliable predictive factors for adolescent and adult psychopathology, impaired health and quality of life among adults,” (Lippard, 2020).

Prevalence and Impact

It is estimated that one in four children will experience child abuse or neglect at some point in their lifetime, and one in seven children have experienced abuse over the past year. In 2016, 676,000 children were reported to child protective services in the United States and identified as victims of child abuse or neglect (Lippard, 2020). However, it is widely accepted that this data significantly underestimates the actual prevalence of childhood maltreatment. How does a 5-year-old report sexual abuse? Nevertheless, the best available evidence reveals that Adverse Childhood Events (ACE’s) currently impacts 1 in 7 children. To make matters worse, the COVID-19 pandemic has further exasperated family dysfunction, and elucidated the increasingly violent and amoral culture in which no traditional belief system can exist without tumult and claims of victimhood, or claims of some sort of  “…ism.”

Yet, the outcome associated with growing up in this toxic culture is a prevalence of psychopathology never imagined, in which suicidality among children and teens is skyrocketing as a result of childhood abuse, neglect and maltreatment at the hands of older teens and adults. The life trajectory for these children is determined by the toxic environments where trauma and child abuse occur in the shadows.  As a result, traumatized children and adolescents cease being future-oriented, and become narrowly focused and hyper-vigilant as they struggle to cope with isolation, fear, sadness, self-loathing, and hopelessness. When these conditions persist, neuroadaptive changes occur wherein the emotional, survival-driven limbic system becomes their primary locus of control. Accordingly, their existence is organized around the trauma or abuse, or by attaining relief from the fear and persistent emotional pain.

Another study by Nemeroff et al. (2015), Professor of Psychiatry and director of the University of Texas Institute for Early Life Adversity, reported that abuse during childhood is associated with:

  • Reduced life expectancy. Increased risk for neuropsychiatric illness, such as addictive disease, depression, anxiety, panic, post-traumatic stress disorder (PTSD) and suicidality.
  • Cardio-metabolic disease, including heart disease, stroke, obesity, and diabetes.
  • Certain forms of cancer.

Research has shown that there is a biological connection between trauma and the human inflammatory process which is designed to protect us from acute infection and injury. But emotional and physical trauma, especially among children, can become chronic conditions, such as PTSD, treatment resistant depression, and increased suicidality.

The role of inflammation and increased vulnerability to debilitating conditions especially among children and adolescents is poorly understood, but is associated with more illness, poor quality of life and premature mortality.

Trauma, or the cumulative effect of ACEs, evokes an inflammatory response along the same neural pathways that are triggered by infection.

How? 

When the fear or survival system is triggered, it causes the release of pro-inflammatory, adrenalin, cortisol and cytokines, which are designed to fight infection. But the emotional effects of persistent trauma are neuroadaptation and the non-acute flooding of immune cells, such as natural killer (NK) cells, which normally release interferons which provoke contiguous cells to attack the pathogen, such as a virus or bacterium. When these cells are triggered by the survival system of the brain, chronic inflammation creates its own pathology. Over time, repetitive acts or thoughts of trauma can reinforce the activation of the immune system, leading to systemic tissue damage and organ system malfunction (Beydoun, 2019).

Eventually trauma exacts a hefty toll on the function of the central nervous system, degrading the innervation and function of the frontal brain. Evidence from functional MRI (fMRI) reveals that increasing levels of inflammation, as measured by C-reactive protein (CRP) levels, interferes with the integrity of neural networks in the frontal lobe, namely the executive function which serves to initiate healthy goal directed behavior (Wersching, 2010). Over time, this can lead to poor performance, self-loathing and neuropsychiatric illness. Indeed, meta-analysis by Lippard and Nemeroff (Am J Psychiatry. 2020) found a robust association between traumatized children and the development of mood and anxiety disorders, post-traumatic stress-disorder (PTSD), personality disorder, and of course Substance Use Disorders (SUDs) which nearly always co-occur with trauma and abuse among children and teens.

Impact of Trauma on Brain Development 

Starting at the onset of puberty, the human brain experiences accelerated growth until completion just before age 30.  The human brain develops from the back (the cerebellum) and is completed in the frontal cortex. During puberty, a process called myelination begins, in which neurons are pruned then sprout billions of new neural connections. Myelin is a fatty, insulating substance that coats the interconnecting fibers of the nervous system. This allows for more rapid transmission of electrical signals, effectively creating a robust bandwidth and allowing for more information to be processed in a fraction of the time. Of particular interest to us is the development and innervation of the frontal cortex, which is uniquely human, and where the highest level of thinking, reason, morality, and inhibition of primitive hedonic drives occurs. Under normal development, a child, with the help of actively involved, loving parents, morphs from a self-absorbed hedonically driven child or young teen, into a responsible young adult who exhibits self-control which is evidenced by demonstrating the ability to delay gratification, engage in executive function, and experience empathy for others.

A healthy and well innervated frontal cortex provides ample processing capacity necessary for complex decision making, empathy, abstraction and executive function and enables the ability to inhibit the primitive survival-driven urges of the limbic system. When our locus of control is a healthy frontal cortex, the individual’s choices and behavior become increasingly reasoned and value driven. This mindset is necessary for prosocial functioning and goal-directed behavior.

As mentioned, emotional trauma and the cumulative impact of ACEs initiate the inflammatory response. But the pathogen (in this case, the trauma and ensuing neuroadaptation) leads to the chronicity associated with trauma, also known as PTSD. The mechanism of how emotional trauma fails to resolve and become chronic is not clear. What is clear is that unresolved trauma leads to chronic inflammation and creates its own unique pathology (Kiecolt-Glaser, 2011)

Meta-analysis by Lippard and Nemeroff (2020) found a robust association between traumatized children and the development of mood and anxiety disorders, post-traumatic stress-disorder (PTSD), personality disorder and of course Substance Use Disorders (SUDs), which almost always co-occur with the aforementioned psychopathology. Another review by Lippard and colleagues summarized current data on the interactions of childhood maltreatment and risk for mood disorders, highlighting potential strategies that could be targeted for early intervention and prevention.  This therapeutic framework provides mental health practitioners with a clinically relevant basis for choosing trauma-specific intervention strategies for emotionally and physically abused or neglected children. Clearly, Lippard’s analysis demonstrates that childhood abuse, neglect, and maltreatment is statistically associated with neuropsychiatric disorders during adolescence and early adulthood. Today, this association is now an expected outcome, in part due to the easy access to intoxicants as well as the abundance and easy access to highly processed comfort food (which is another source of self-medication in genetically vulnerable persons, mostly females as evidenced by binge eating disorders, obesity and diabetes among adolescents).  For others, sexual gratification provides a pseudo-intimacy that temporarily soothes the loneliness experienced by traumatized children and teens. Gambling and dangerous risk-taking behaviors promise short-term respite for many who have been wounded by trauma.

Hypodopaminergia 

These compensatory behaviors all elicit an acute, dopaminergic surge that is part of the neurotransmitter cascade which also modulates the effects of serotonin and norepinephrine. The resulting short-lived, pleasurable state caused by the abuse of intoxicants is commonly described by our traumatized patients as a short “vacation” from the emotional wounds they have endured. However, when dopamine is activated and elevated far beyond what the natural rewards could attain, a resulting depletion occurs which leaves the abused and perhaps addicted person with less dopamine. The resulting anhedonia, increasingly limits the positive reward normally attained by natural experiences. In short, life becomes increasingly gray, boring and devoid of joy or happiness.  Without intervention, depression and fear become intolerable, and suicidal thinking increases.

Recent breakthroughs in genetic testing, such as the Genetic Addiction Risk Scale (GARS) developed by Kenneth Blum and colleagues, allow us to identify Single Nucleotide Polymorphisms (SNPs) in candidate genes responsible for the coding for neurotransmitters and neurohormones that mediate mood states. Blum’s group helped identify the COMT gene which provides instructions for making an enzyme called Catechol-O-Methyltransferase. An estimated 25-30% of Caucasians of European ancestry have a COMT gene variation which limits their ability to remove catecholamines, a specific type of molecule that includes dopamine, norepinephrine, estrogen, etc.) This “slow” variation of the COMT gene is called Met/Met, AA, or +/+. COMT is also associated with increased levels of cortisol and adrenalin which keeps traumatized persons in a hyper-vigilant, stressed state.

Over time, traumatized persons cannot experience the reward, focus, energy and joy they would otherwise experience. Those with the variant COMT gene are genetically at risk of developing what Blum named “Reward Deficiency Syndrome” (RDS), the final common pathway for all the addictive diseases. Clearly, genetically vulnerable persons exposed to ACEs are more likely to develop RDS.

Most experts agree that prevalence data are woefully underestimated, as physically, emotionally, and sexually abused and neglected children feel frightened and powerless and therefore remain in silent desperation.  If we could put a simple label on what abused and neglected children learn and believe about themselves, it is this:

“I am not very important, or why would those who are supposed to love and protect me continue to hurt me? Something is wrong with me; I must be unlovable”.

Children who believe this about themselves initially turn these feelings inward and believe they are not worthwhile. By early adolescence, most boys begin to express their hurt as anger, acting out, and finding alternative ways to feel validated and important. Many girls do the same, yet the best available evidence suggests that girls more often turn this hurt and shame inward and engage in self-soothing, self-destructive behaviors and ultimately suicidality.

Regrettably, neuropsychiatric conditions, including addictive disease, are now ubiquitous among teens who have been abused or traumatized. For these deeply wounded children and teens, the use of intoxicants is the fastest and most reliable coping strategy available to them, in that getting high, temporarily relieves their emotional pain. Moreover, many find drug-using peers in whom they feel a connection, allowing them to engage and feel some value, as most share similar experiences. Yet, seldom is anything resolved through these maladaptive coping strategies. Their lives continue to become increasingly pathological, spiraling out of control while experiencing failure and recrimination for the consequences of their maladaptive behavior.

Suicidality 

The suicidality data support this observation. The extent to which wounded and tormented adolescents cope with trauma and abuse is changing as families no longer provide the time to engage, love, support, supervise and protect their children, as was commonplace in generations past.  As a result, suicidality among teens has tripled since 2006, as more children grow up amid the “new normal” where divorce is no longer associated with any stigma, or much concern for the children, and families, like gender, have become any arrangement of persons that create convenience and personal freedom for the adults involved. As a result, the children suffer the brunt of the consequences, yet have no say in how their family is organized or constituted. We mention this because, among the children and teens who leave notes before they kill themselves, most cite their family dysfunction and parents’ divorce among the top 5 reasons why their life has become so unbearable that death is preferable to the pain, emptiness, and loneliness they endure. Addictive disease or mental illness within their family, bullying, rejection from peers, and being used sexually then discarded round out the main factors cited among children who take their lives.

As with all disease, some are at greater risk than others. Some children possess the capacity to excel in something that provides approval, affirmation and self-worth.  Sports, music, academics, and faith are examples of empirically derived protective factors that enable these children to escape the debilitating effects of early life trauma. But the wounds are still there and will certainly become symptomatic later in life (Sachs-Ericsson, 2016).

The most recent and best available evidence suggests the following:

  • Children experiencing emotional abuse and neglect may never be evaluated for it, as this form of maltreatment is less likely than physical and sexual abuse to cause physical injury and thus may never be identified. But these children are traumatized nevertheless, and suffer from adverse health effects and poor outcomes.
  • Child abuse seldom occurs in isolation. Rather, most abused children experience several forms of abuse and often are raised in a dysfunctional family system.
  • Cross-sectional and more recent longitudinal studies have shown that childhood maltreatment is more commonly diagnosed among patients with Substance Use Disorders, depression and anxiety disorders, PTSD, and personality disorders. Up to 46% of study participants were diagnosed with depression and 57% with bipolar disorder. (Lippard and Nemeroff, 2019).
  • Childhood maltreatment also increases the risk for medical disorders such as coronary artery disease, myocardial infarction, cerebrovascular disease, stroke, type 2 diabetes, asthma, and certain types of cancer.
  • Victims of child abuse and neglect have a significant reduction in life expectancy.
  • Bullying, including cyberbullying, is a form of abuse that may trigger suicide, particularly among female individuals, but more research is needed.
  • Although maltreatment at any time during childhood significantly raises the risk for mood disorders, research suggests that the worse outcomes occur when abuse or neglect begins earlier in life and persists into adolescence (Meiers, 2020).
  • Among those with diagnosed mood disorders, childhood maltreatment is linked to earlier age onset of maltreatment and experience depression and anxiety disorders earlier in life. Moreover, early onset is associated with recurrence, greater comorbidities and greater symptom severity, including suicidal ideation and attempts, and poorer response to treatment.
  • Various neurobiological associations may mediate the associations of childhood maltreatment with development of mood disorders, which may be reflected in structural and functional brain changes, such as lower gray matter volumes and thickness in the ventral and dorsal prefrontal cortex, including the orbital frontal and anterior cingulate cortices, hippocampus, insula, and striatum.
  • White matter structural integrity within and between these regions may also be affected, with varying patterns of injury according to varying types of maltreatment and on the child’s age.
  • Underlying mechanisms may include persistent changes in the hypothalamic-pituitary-adrenal axis and related neuroendocrine pathways that regulate endocrine, behavioral, immune, and autonomic responses to stress (Menke, 2018).
  • The association of childhood maltreatment with psychiatric disorders may also be mediated by C-reactive protein and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, which may predispose individuals to mood disorders and to a more chronic and severe disease course. For example, patients with depression with elevated inflammatory markers might benefit from anti-inflammatory medications, but more research is needed (Hori, 2019).
  • Several candidate genes and negative environmental influences such as substance use may affect disease vulnerability and course whereas social support and secure attachments may mitigate risk for depression (Blum, 2018).
  • Intergenerational transmission of trauma and psychopathology, such as may occur in Holocaust survivors, involve epigenetic mechanisms altering ova and sperm cells, so that the offspring may reflect some genetic effects of their parent’s trauma. More study is needed (Youssef, 2018).
  • Research to date has suggested modifiable neural mechanisms that may inform more effective strategies for prevention and treatment (Al-Ezzi, 2020).
  • ACE investigators conclude that lowering the high prevalence of childhood maltreatment could markedly reduce medical and psychiatric disease burden on our society (Spinhoven, 2010).
  • Physicians should therefore perform detailed assessments of childhood trauma history, understanding that children and teens with such history are unlikely to volunteer it unless asked specific questions. Trauma-informed treatment is finally getting some traction among pediatricians and primary care physicians.
  • Educating clinicians, guidance counselors and para-professionals on trauma-informed approaches is of key importance.
  • Interventions for children suspected of ACEs should include family assessment, particularly in the presence of known risk factors such as single parenthood, poverty, substance abuse or mental illness within the family of origin.
  • Future research priorities should include determining reversibility of brain and somatic changes linked to
    • Childhood maltreatment
    • Developing optimal treatments
    • Designing assessment protocols to identify at-risk children by genome-wide scanning to detect candidate genes and genetic risk.

Treatment 

Regrettably, little today is being done on the prevention side, and new treatment modalities are seldom used in our current broken health care system. At best, the prevailing care environment offers only acute, life-saving care for the end stages of chronic and often deadly diseases, which all share the origin of Reward Deficiency Syndrome. Thus, treatment today is unfortunately neither standardized nor widely available for large segments of the population.

Yet in spite of growing awareness, the lack of prevention is leading to heightened social discord and unrest. Expert panels suggest increased funding for psychologists and school resource officers who can only address the carnage and consequences of a cohort of millions of children who long for human connection and love. Our culture is making it easy for children to settle for destructive alternatives that provide temporal feelings of significance and self-worth during adolescence, the time when finding one’s place among the human herd is the most critical nexus in their development (Erickson, 1958, 1963).

Erickson postulated these development stages are sequential, and milestones of crisis in nature serve the development by involving the psychological needs of the individual in conflict with the social world. Erickson was clear, successful completion of each stage results in a healthy personality and the acquisition of basic virtues. These are characteristic strengths which the ego can use to resolve subsequent crises.

Failure to successfully complete a stage can result in a reduced ability to complete further stages, resulting in an unhealthy and disorganized personality and sense of self.  These stages, however, cannot be resolved successfully at a later developmental, i.e., early childhood, the conflict cannot be resolved by the individual alone. A great deal of skilled therapy is needed.

The good news is that there are effective treatment modalities which show promise to durably modify brain structure and function for the better. Until we find a way to reduce ACEs and reinvigorate the family as a functional source of peace, these strategies show hope to rescue and recover patients from the effects of physical and emotional trauma. We are at the dawn of a new era of neuromodulation, and the following techniques hold great promise to alleviate human suffering.

Eye Movement Desensitization and Reprocessing

Eye Movement Desensitization and Reprocessing (EMDR) is based on the theory of Adaptive Information Processing (AIP). This theory asserts that humans process new experiences via several neural networks which are interconnected. New information binds to existing learning and subsequent emotions in existing memory network. EMDR is typically administered weekly in 60-90-minute individual sessions over the course of approximately 2-3 months. The exact length of treatment varies based on the individual’s own needs, resilience, genetics, and response to therapy.

Although the exact therapeutic mechanism of EMDR is currently unknown, what is clear is that it exerts a beneficial modulatory effect on the survival neural networks, down-regulating the recruitment of stress hormones and their downstream actions. Through the effect of progressive reconditioning, the negative physiological effects of traumatic memories can be extinguished through EMDR.

Transcranial Magnetic Brain Stimulation 

The recent innovation of Transcranial Magnetic Brain Stimulation (TMS) with theta wave bursting (Blumberger, 2018) has been shown to be more effective than pharmacotherapy in clinical trials involving the treatment of PTSD and Treatment Resistant Depression (TRD) (Croarkin, 2019). TMS works by mediating brain wave activity during short sessions that induce a magnetic current in the cerebral cortex, creating salutary changes in the brain’s electrical fields. These changes can have enduring effects that improve function of brain tissue and neurotransmitter stores.

Ketamine

Studies in animals reveal that chronically elevated levels of stress cause a functional disconnection between neurons. Because proper function of the frontal lobes is crucially dependent upon the integrity of synaptic connectivity, it’s not hard to see how stress-related changes to these circuits can allow the survival brain, or limbic system, to run unchecked. This may explain many of the facets of PTSD, which include a loss of interoception, decreased self-awareness, and over-activation of stress response physiology.  Ketamine is a tranquilizer used for over 60 years as anesthesia, primarily on children and during animal surgery. The dark side is that it was a popular drug of abuse as a rave drug, and recreational hallucinogen when taken in large doses. In the therapeutic setting, it turns out to be highly effective in rapidly reversing the signs and symptoms of depression and suicidality. Ketamine inhibits the N-methyl-D- Aspartate system, which makes it unique from current antidepressant formulations, which all toll have about a 40% efficacy.  It is thought Ketamine’s effect hastens the reconnection of neuronal synapses, in as little as 15 minutes and alleviates severe refractory depression and suicidality after an infusion of 45 minutes. Ketamine, by way of infusion, intranasal inhalation and more recently a sublingual form may indeed be a highly efficient strategy to rebuild brain tissue and reestablish its regulatory ability to overcome the effects of chronic, unrelenting stress, depression and PTSD. (Krystal, 2017).

Summary

There is a complex and seemingly sinister interplay at work affecting the development of children and adolescents, and altering their trajectory into adulthood.  Adverse Childhood Events are causing neuroadaptations and possibly epigenetic changes resulting in severe neuropsychiatric disease and increase mortality.  Negative cultural and environmental influences are being normalized as we are witnessing the impact that decades of emotional trauma in lock step with the decimation of the intact loving and engaged family.

Reward Deficiency Syndrome, of which addictive disease is grabbing most of the headlines is often the first time a child or teen’s psychopathology is noticed and addressed. For traumatized and neglected children, it is often too late by this time. The good news is that advances in basic neuroscience is producing technological solutions that provide benefits beyond currently available pharmacological treatments. More research is needed. However, the elephant in the room is the absence of parents in the lives of their children. A mother and father’s love, protection, trustworthiness, and availability are irreducibly necessary, yet so simple that we have missed it. The associations of involved, engaged parents and the well-being of children is axiomatic, whereas wounded, emotionally abused children become self-destructive teens and young adults. The collective impact on our society cannot be understated. Prevention, in terms of neuropsychiatric illness, has seldom been given more than lip service. Yet the undeniable positive influence of loving, intact and hands-on parenting, is undoubtedly the best protection and prevention available. This is not a medical problem, per se’. It’s a matter of social and family priorities.

Psychologist, Dr. James Dobson said it best when asked about parental involvement, “which is more important to the well-being of children- quality time, or quantity of time”. He responded, “Children require quality time from their parents…and a lot of it.” This is simply not happening and our kids are paying the price, which in turn is destroying the social fabric of family and community. We can and we must do better.

Dr. Drew Edwards is the co-founder and Chief Clinical Officer at the Neurogenesis Project, dedicated to using advances in neuroscience to help for those suffering from neuropsychiatric illness, e.g., addictive disease, mood disorders and brain injury. Formerly he was Assistant Professor of Psychiatry and Health Behavior at the Medical College of Georgia; and previously Associate Director of Psychiatry at the University of Florida where he provide clinical instruction for residents and post Doctoral fellows in the Division of Addiction Medicine. Dr Edwards has recently co-authored a chapter on neurogenetic testing for Cambridge University Press, and another textbook chapter for the American Psychological Association. 

Dr Sean Orr is Co-founder and Chief Medical Officer at The Neurogenesis Project. Previously he served as Chief of Neurology in major medical center. Trained as a neurointensivist and neuroenovascular neurologist, Dr Orr was at the forefront in developing life saving stroke centers and neuro-critical care programs  As a trauma and concussion expert, Dr Orr served as neurologist for an NFL franchise where he saw first hand the undeniable association between concussion, depression and substance use disorder.  

With their combined skills and training Dr Orr and Dr Edwards are developing innovative clinical modalities to treat brain injury, depression, PTSD, and addictive disease. https://www.neurogenesisproject.com