Neurobiology of ADHD and Comorbidities
Neurobiological research indicates it is reasonable to consider ADHD as a condition that falls under the “reward deficiency syndrome” (RDS) diagnostic umbrella (Blum et al. 2008), as symptoms of poor concentration stem from the brain’s inability to release sufficient amounts of dopamine (DA) in areas of the frontal lobes and limbic system to provide a feeling of reward when applying and/or maintaining focus on tasks at hand.
DA is the neurotransmitter most linked to attention and the ability to experience pleasurable emotions and sensations; It allows for general feelings of wellbeing, tempering of unpleasant emotions, good concentration, and optimal thought organization. For this reason, certain individuals with ADHD are more likely to experience depression. They may also develop thrill-seeking behaviors and engage in risky activities that result in an increased release of dopamine, such as high-risk sports, gambling, hypersexual behaviors, excessive internet video gaming, aggressive behavior, drug use, excessive shopping, and binge eating. Since DA is fundamental to producing pleasure and it impacts the activity of natural opioids in the brain, it also helps decrease feelings of uneasiness and drug withdrawal. People with RDS are therefore at higher risk of addiction to recreational or illicit drugs, as they may have a harder time stopping them (Blum et al. 2008).
Certain stressors, such as seeing a bear jump out of the bushes, can trigger spikes in DA and norepinephrine (NE) that may capture and sustain one’s attention. However, there is no continuous environmental stressor that can help an individual with ADHD focus. Chronic stress equates to flooding the brain with NE and DA for an extended period of time, and this eventually leads to depletion of NE and DA supplies and thus low levels of these neurotransmitters in the prefrontal cortex.
It is important to note that people with ADHD are, at times, under-stimulated by certain modes of teaching, experiences, or repetitive tasks. Those who tend to seek out strong sensations are also likely to experience stimulation overload in busy settings flooded with tactile, visual, and auditory cues (Miller and Blum, 2008). Under these circumstances, individuals with ADHD may demonstrate a heightened awareness of incoming stimuli. Due to their decreased ability to separate irrelevant distractions from key information, they may become overwhelmed, anxious, and frazzled — resulting in panic, irritability, frustration, impatience and/or anger.
Affected Brain Regions
It is interesting to note that several regions of the frontal-subcortical, striatal, and hippocampal areas of the brain are smaller and show less activity in individuals with ADHD. Researchers have found that it is the ineffective activation by NE and DA of the dorsolateral prefrontal cortex that projects to the striatal complex that seems to cause difficulties with Selective Attention; of the dorsal anterior cingulated cortex projecting to the striatal complex and then to the thalamus that seems to cause issues with Sustained Attention; and suboptimal activation of the orbitofrontal cortex, striatal complex, and thalamus that seems to lead to impulsivity-hyperactivity symptoms.
The Thalamus is predominantly linked to information processing and relay of information to the prefrontal cortex and to structures of the limbic system associated with memory, emotion, and arousal. It thus seems reasonable to conclude that disruptions in the thalamic area of the brain may cause difficulty with the filtering and organizing of information as well as insomnia, energy disturbances, emotional discomforts, and forgetfulness. Limbic Structures linked to the Thalamus:
- The Hypothalamus occupies a lower part of the thalamic region and is strongly associated with appetite regulation and sex drive. Disruptions in the hypothalamus may lead to changes in libido (e.g., hypersexuality) and appetite disturbances that are difficult to control (e.g., binge eating).
- The Amygdala is considered to be the primary center for emotions and survival instincts (e.g., fight or flight) and motivation. Disruptions of the amygdala may lead to increased fearfulness and anxiety, aggressiveness and impulsive anger, excessive competitiveness and/or a tendency to establish dominance.
- The Hippocampus seems to be mainly involved in determining ability for attention, long-term memory, learning, and orientation. Damage to the hippocampus can lead to difficulty in forming and retaining memories and learning new skills.
- The Striatum, which is part of the basal ganglia and is considered to be an important part of the brain’s reward center, helps spur motivation by providing positive feelings in response to certain stimuli. It is also closely associated with emotional regulation and mastery as well as addictive behavior. Interestingly, low availability of DA in some parts of the brain known to be affected in people with ADHD can trigger compensatory mechanisms that produce too much DE in the basal ganglia, further increasing hyperactivity and impulsivity as well as often concomitant tics reflecting Tourette’s syndrome, another disorder of RDS (Blum et al. 2008).
- The prefontal cortex also receives information from the Thalamus and is mostly correlated with attention, time management, and behavioral inhibition, allowing for appropriate social behavior. It is believed to be the ultimate guide that links thoughts, actions, and emotions in ways that facilitate more complex and socially appropriate behaviors, reasoning, problem solving and making decisions. Regions of the prefrontal cortex linked to the Thalamus:
- The Dorsolateral Prefrontal Cortex has been found to be disrupted in people with schizophrenia, major depressive disorder, and anxiety disorders.
- The Orbitofrontal Cortex plays an important role in regulating impulsivity, compulsive behaviors, and working memory (which is the part of short-term memory concerned with transient holding, processing, and manipulation of information involved in decision making). The orbitofrontal cortex has also been associated with symptoms of anxiety disorders, oppositional defiant and conduct disorders, negative symptoms of schizophrenia, and impulsivity in bipolar mania, impulsivity and compulsivity in substance abuse, and suicidality in major depressive disorder.
Since many regions of the brain are involved in ADHD, and DA is found throughout the brain at different levels, it seems logical that people with ADHD may have other psychiatric conditions in the same regions that are associated with DA regulation. Individuals with ADHD seem to be at higher risk for developing major depressive disorder, anxiety disorders, obsessive-compulsive disorder, oppositional defiant disorder, conduct disorder, bipolar affective disorder, learning disorders, and substance abuse disorders, including alcoholism and drug addiction (Biederman J, Monuteaux M, Spencer T, Wilens T, Faraone S. Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics 2009; 124: 71-78). People with ADHD are also much more likely to have bicycle or motor vehicle accidents, and they have a significantly higher risk of ending up in an emergency room from accidental injury (DiScala, C, Lescohier I, Barthel M, Li G. injuries to children with ADHD. Pediatrics 1998; 102: 1415-21).
Research has identified the following biological risk factors as increasing the risk of children being born with a likelihood for ADHD: preterm delivery, low birth weight, severe early deprivation/malnutrition, lead exposure, maternal smoking in pregnancy, fetal alcohol syndrome, and TBI (Biederman J, Faraone S, 2005; Faraone et al. 2010, Swanson et al 2007). In addition, oxygen deprivation of the fetus caused by long-lasting prenatal stress experienced by the mother or of the baby soon after birth has been found to be a likely risk factor for ADHD.
ADHD is more prevalent in some families, with approximately 50% of parents with ADHD having children with ADHD. Furthermore, researchers have observed that half siblings with only one parent affected by ADHD, having been raised in the same environment as their ADHD- affected siblings, have a significantly lower risk of developing ADHD (Blum et al. 2008). These studies suggest that ADHD is highly hereditary and unlikely to be a learned dysfunction (Blum et al. 2008).
Several genes have been associated with the production, release, and absorption of DA and thus to the development of ADHD. For example, abnormalities in the DRD2 dopamine receptor gene can lead to the creation of an insufficient number of DA receptor sites for optimal DA absorption in certain areas of the brain, which leads the brain to adapt to this decreased absorption capability by decreasing its production of DA in those regions (Blum et al. 2008). Although one abnormal gene can affect the brain profoundly, research suggests that certain clusters of gene abnormalities must be present for an individual to have ADHD (Blum et al. 2008). To date, genes identified as playing a role include:
- Dopaminergic genes determining the production, release and/or absorption of DA: DRD2, DAT1, DBH (Blum et al. 2008), DRD4, DRD5, COMT, dopamine transporter SLC6A3,
- Noradrenergic: DBH, ADRA2A
- Serotonergic: 5-HTT, HTR1B, HTR2A, Serotonin transporter SLC6A4, serotonin receptor HTR1B
- Cholinergic: CHRNA4
- Central nervous system development pathway synaptic-vesicle transporter SNAP25 and BDNF protein modulator genes.
The type of ADHD that a person has and the type of comorbid conditions that one may be predisposed to depend on which genes are affected and to what extent they are affected. Interestingly, some studies have determined that the level of dysfunction of DRD2, DAT1, and DBH genes in particular seems to be proportional to the intensity of symptoms experienced by people with ADHD (Blum et al. 2008).
Why Does ADHD Start Between the Ages 6 and 12?
Brain connection density, caused by the synaptic interconnections between neurons, rapidly increases in the prefrontal cortex by age 6, and up to half of these synapses are eliminated in a phenomenon called pruning by adolescence. It is theorized that a faulty selection process of which synapses should be kept and which should disappear is one of the primary causes leading to the onset of ADHD.
Can ADHD be Cured?
It is estimated that 8 to 12% of children have ADHD, as opposed to 4 to 7% of adults. This suggests that approximately 50% of adults grow out of their ADHD. It is a well-known fact that in individuals with ADHD, impulse control, attention spans and hyperactivity improve with age (Faraone S, Biederman J, Mick E. The age dependent decline of ADHD: a meta-analysis of follow up studies. Psychological Medicine, 2006, 36: 159-65). Over the last few decades, neurologists have confirmed that the brain is “plastic” and thus it can reshape itself over time. In other words, you can teach an old dog new tricks! Considering that brain connections determine and solidify our habits and that habits can be broken as new habits are formed, one predominant theory to explain why some people seem to grow out of their ADHD is that these individuals compensate for the faulty pruning of their synapses from ages 6 to12. They exercise their focus and memory by engaging in activities that require more concentration and retention of information, which creates new habits that increase organization, favor concentration, and thus lead to the creation of new replacement synapses overtime. These helpful habits allow adults to become less forgetful, less likely to misplace their belongings, and better able to avoid distractions and focus on tasks at hand. However, it takes some ability for concentration and organization to create helpful functional strategies and to practice them until they become habits. Sometimes, people with a severe form of ADHD need medications to give them a head start. Proper treatment increases concentration and organization, facilitating the development of habits that lead to the development of helpful, long-lasting brain connections. This is why treatment during childhood is recommended, as it is believed to decrease the risk of symptom progression, and to help develop compensatory mechanisms early on that decrease intensity of symptoms in adulthood.
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The Center of Excellence in Co-Occurring Medicine is an outpatient clinic in Beaverton, Oregon, that offers expert, compassionate psychiatric care and substance abuse treatment.
Ms. Rosengarten is Director of Clinical Operations at the Center of Excellence in Co-Occurring Medicine. She is a Psychiatric and Mental Health Nurse Practitioner with a long history of leadership in behavioral health and clinical practice, which reflects a deep commitment to the well-being of her patients. Prior to joining the Center of Excellence, Ms. Rosengarten served as Chief of Behavioral Health at Harvard Vanguard Medical Associates in the greater Boston area.