All About ADHD

What is ADHD?

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder of attention, concentration, impulsivity, and hyperactivity. ADHD is one of the most heritable psychiatric disorders and the most common behavioral disorder in children.

Although ADHD was originally thought to be a disorder exclusively in children, we now know that approximately two-thirds of children diagnosed with ADHD experience impairing symptoms in adulthood. In school-aged children/adolescents, the prevalence of ADHD is about 5-7%. There are different types of ADHD depending on whether symptoms are predominantly inattentive, hyperactive, or both. The combined type is the most common type in children and adolescents.

Males are more likely diagnosed in childhood and adolescence, likely because males display more hyperactive symptoms than females and therefore are more likely to be referred for evaluation.

Females usually have more inattentive symptoms and aren’t diagnosed until later in life. This is supported by the more equal prevalence of ADHD in adult males and females. The inattentive type is the most prevalent type in adults (about 47% of cases). The apparent decrease in hyperactive-impulsive symptoms as individuals age is likely related to the maturation of brain circuits in the cerebral cortex as people age. 

Symptoms of ADHD include inattention, hyperactivity, and impulsivity that interferes with an individual’s relationships, work, schooling, or other important areas of functioning. 

Inattention: 
  • Difficulty with attention to detail
  • Often makes careless mistakes
  • Difficulty listening when spoken to directly (e.g., mind seems to wander elsewhere).
  • Difficulty following directions
  • Difficulty organizing tasks and activities
  • Often avoids tasks requiring sustained mental effort
  • Often loses things/personal items 
  • Often is easily distracted
  • Often forgetful about daily activities
  • Often has difficulty sustaining attention
  • Often bored or loses interest quickly
Hyperactivity:
  • Often fidgets or shifts in seat (example: meditation can be very difficult for those with ADHD)
  • Often leaves seat in situations when remaining seated is required 
  • In children, often runs about or climbs in situations where it is inappropriate
  • Often unable to play or engage in leisure activities quietly
  • Internal restlessness or feeling constantly on the go
  • May talk excessively
Impulsivity:
  • Often finishes sentences or blurts out answers
  • Often has difficulty waiting his or her turn
  • Often interrupts others 
  • Often impatient 

What is Attention?

Attention is a cognitive function. Attention describes the process of determining the importance of various stimuli and selecting the stimuli most relevant to the task at hand. Attention is an important component of our consciousness.

Which Brain Areas are Involved in Attention?

Although neural networks throughout the entire brain contribute to most cognitive functions, there are some areas of the brain which appear to play a greater role in remaining attentive. These areas include the prefrontal cortex (which is part of the frontal lobe or frontal region of the brain) and the regions “underneath” or “embedded” in the frontal lobe such as the cingulate cortex and its connections with the nondominant parietal lobe. 

Reward and Impulse Control

Controlling the impulse to take an immediate, smaller reward rather than waiting for the larger, delayed reward is essential for completing any project. People who cannot control these impulses often fall behind. In the famous Stanford Marshmallow Experiments of the 1970s, Walter Mischel, a psychologist, conducted a very interesting experiment:
 
Four-year-old children were given one marshmallow. These children were told that they could either eat the marshmallow now or wait until the research assistant returned from an errand and receive TWO marshmallows (oh my!). Some children couldn’t wait for the assistant to return and immediately ate the marshmallow in front of them. Others waited a little but eventually ate the marshmallow. And yet others waited until the assistant returned and were rewarded with TWO marshmallows (what a reward!). 

The children in the study were followed into adolescence and adulthood. It turned out that the children who were better at inhibiting the impulse to immediately eat the one marshmallow were more resilient, confident, and dependable as adolescents. They also scored higher on standardized tests such as the SAT. While a controversial study with some methodological problems, the results were interesting, nonetheless.

Dopamine and Norepinephrine 

Dopamine and norepinephrine are two very important brain chemicals involved in attention, movement, and impulse control. These two chemicals work together to filter out irrelevant stimuli while enhancing the relevant stimuli. In individuals with ADHD, these two chemicals appear to be imbalanced or “out of tune.” By enhancing these brain chemicals with medications, therapy, and neurofeedback, we can improve symptoms dramatically!

Impulsivity 

Attention and impulsivity are partially controlled by dopamine (DA) in an area of the brain called the Nucleus Accumbens (NAc). The NAc, which is part of the striatum (another brain region), is the part of our brain responsible for pleasure, motivation, and reinforcement. Stimulant medications such as Concerta, Ritalin, Focalin, Adderall, Dexedrine, and Vyvanse increase dopamine release in the NAc to improve our ability to control impulsive behaviors. Interestingly, rats with damage to their NAc are more impulsive–they almost always choose the immediate reward.

Brain Changes in ADHD

Changes in the prefrontal cortex (PFC) and striatum are the most common abnormal brain findings reported for ADHD. Judith Rapoport’s National Institute of Mental Health (NIMH) neuroimaging studies have revealed interesting findings in children with ADHD. Children with ADHD, on average, have smaller brain volumes by about 5% and also have smaller cerebellums (the little brain in the back of the brain). Importantly, the trajectory of brain volumes did not change as the children aged, nor was it affected by the use of stimulant medication.
 
When comparing children with and without ADHD, there was significantly greater activity in the parietal and frontal lobes of children without ADHD during an attention task (see figure below). This tells us that decreased activity in the frontal and parietal lobes may be partially responsible for inattentiveness. That is, these brain areas aren’t activated enough or “online” during attention-requiring tasks. 

ADHD & Gender Differences

The symptoms of ADHD present slightly differently in males and females. A list of differences is provided in the table below.
 

Consequences of Untreated ADHD

  • A World Health Organization survey estimated that 3.5% of all workers suffer from ADHD yet only a minority of these workers received treatment. 
  • Young adults diagnosed with ADHD but not treated are less likely to enroll in college or graduate from college.
  • Students with untreated ADHD are more likely to be on academic probation and have a lower grade point average.
  • Adults with untreated ADHD experience difficulties in all aspects related to employment
  • ~20% of parents of children with ADHD have ADHD themselves (Faraone et al. 2000).
  • Untreated ADHD has been associated with significantly increased risk of developing substance use disorders
  • Untreated ADHD has been associated with risky behaviors resulting in traffic tickets, motor vehicle accidents, and other injuries related to impulsivity and altered decision-making 

ADHD and Criminality 

  • Studies have estimated the prevalence of ADHD among male prison inmates to be around 40% (Rösler et al. 2004; Ginsberg et al. 2010).
  • In the absence of comorbid conduct disorder, ADHD patients had no higher risk for delinquency than adults with other childhood psychiatric disorders (Gjervan et al. 2012).

ADHD Symptoms in Adults

  • Hyperactivity: Inner restlessness, Talkativeness, Excessive fidgeting, high risk activities
  • Impulsivity: Impatience – “talking without thinking”, difficulty maintaining employment, difficulty maintaining relationships, attention seeking behavior, high risk behaviors, self-medicating
  • Inattentiveness: Feeling bored, indecisive, procrastination, disorganization, easily distracted

Common complaints in Adults with ADHD

  • Common complaints in adults with ADHD include rapid mood swings, difficulties dealing with stressful situations, frequent irritability and frustration, emotional excitability (anger over minor things), relationship problems (short-lived, divorce), and coping with one or more children with ADHD.

**ADHD IS NOT RELATED TO INTELLECT**

ADHD vs Bipolar Disorder

Differentiating ADHD from Bipolar Disorder can be difficult because many symptoms overlap and both disorders often co-occur (that is, many patients have both ADHD and Bipolar Disorder). Below is a table differentiating the two.

Treatment Options For ADHD

  • Medications (Stimulants, nonstimulants)
  • Behavioral therapy 
  • Neurofeedback
  • Biofeedback

ADHD and Substance Use Disorders

NOTE: Stimulants such as amphetamines (Adderall, Dexedrine, Vyvanse) and methylphenidates (Ritalin, Concerta, Focalin) are first-line treatments for adult ADHD. Studies suggest that amphetamines may be more effective for adult ADHD symptoms than methylphenidates. The common belief that individuals with a history of substance abuse shouldn’t be prescribed psychostimulants is not supported by empirical or anecdotal evidence. In fact, proper treatment of ADHD symptoms has been associated with a reduction in substance use. For more information on this, please see the articles below.

ADHD Medication and Substance-Related Problems 

Stimulant ADHD medication and risk for substance abuse

How do stimulants work?

The term stimulant or psychostimulant isn’t well defined. Cocaine, amphetamine, methylphenidate, modafinil, armodafinil, caffeine, and nicotine belong to this class of drugs, which are called stimulants for the marked sensorimotor activation that occurs in response to drug administration. Stimulants are characterized by their ability to increase alertness, heighten arousal, and cause behavioral excitement. Psychostimulants are prescribed for the treatment of attention-deficit hyperactivity disorder (ADHD), narcolepsy, chronic fatigue, depression, and cancer-related fatigue to name a few. Stimulants are also drugs of abuse (such as cocaine, illicit methamphetamine, nicotine, and caffeine).

Let’s take a closer look at psychostimulants and how they work. 

Table of Stimulants

 

Dopamine and Norepinephrine

Neurons are cells in our brain that communicate with each other like telephone wires. Each neuron can communicate with or “talk to” thousands of other neurons using chemicals called neurotransmitters. The most abundant neurotransmitters in the brain are glutamate, which generally excites other neurons, and GABA, which generally inhibits other neurons. Dopamine (DA), serotonin (5-HT), norepinephrine (NE), acetylcholine (ACh), histamine, cannabinoids, and other neurotransmitters play very important roles in altering the communication between neurons.

Interestingly, dopamine (DA) and norepinephrine (NE) are neurotransmitters with important roles in attention, arousal, energy, motivation, pleasure, reinforcement, movement, learning, memory, and mood states.

DA and NE are stored in neurons within small bubbles called vesicles. These vesicles are released into an area between two neurons called the synaptic cleft. DA and NE then bind to receptors located on other neurons (including the same neuron that released them) to communicate a signal. DA and NE are then recycled or “vacuumed” back into the neuron by specific transporters called dopamine transporters (DATs) and norepinephrine transporters (NETs), respectively.

The recycled dopamine and norepinephrine are pumped back into vesicles via the vesicular monoamine transporter 2 (VMAT2) and are stored for the next cycle. Stimulants like amphetamines, methylphenidates, and cocaine increase dopamine and norepinephrine in the synapse by various mechanisms which are discussed in more detail below. 

Amphetamine, AMPH (Vyvanse, Dexedrine, Adderall)

Amphetamine (AMPH) has numerous mechanisms. First, it can be taken up into neurons via the dopamine transporter or norepinephrine transporter which then reverses its actions to promote the release of dopamine.

AMPH also enters vesicles through VMAT2 and displaces dopamine by “forcing” dopamine out of the vesicle and into the cytoplasm. Increased cytoplasmic dopamine concentrations cause passage of dopamine through the DAT into the synapse thereby increasing the dopamine concentration in the synaptic cleft.

Mechanism of Action of Amphetamines

Methylphenidate, MPH (Ritalin, Concerta, Focalin)

Methylphenidate (MPH) acts by inhibiting the dopamine and norepinephrine transporters which increases the concentrations of dopamine and norepinephrine in the synapse.

Mechanism of Action of Methylphenidates

 

Psychostimulants Reduce Noise and Enhance Signals

In individuals with attention and/or concentration problems, there may be a problem with how the brain is processing sensory input. Our brains spend an enormous amount of energy (up to 20-30% of all energy used by your body) processing information below our level of awareness. In fact, only a very small percentage of brain activity contributes to our conscious awareness (roughly 15%). The rest of the activity is all the unconscious processing, integrating, and analyzing of information that ultimately results in complex behavior. 

Much of the brain’s energy is spent “deciding” which signals are relevant and need to be brought to conscious awareness. Think of all the activities we do that we aren’t even aware of. 

While walking down the street talking with someone, do you actively feel your left big toe? Well, no, not unless you have pain or stub your toe. We aren’t aware of our left big toe because it’s irrelevant to what we are doing. But this doesn’t mean those signals are physiologically absent. 

Dopamine and norepinephrine are neurotransmitters in the brain that act like the tuners of a piano. The strings of the piano that create the sounds represent the glutamate and GABA neurons that are the primary excitatory and inhibitory neurotransmitters in the mammalian brain, respectively. Dopamine and norepinephrine are there to tighten the strings so the music sounds good.

No one likes a song that’s out of tune. That is, dopamine and norepinephrine are those “tuners” of the brain–they modulate communication between neurons. They help our brain decide what to ignore and what to focus on.

In fact, norepinephrine in the prefrontal cortex (PFC) plays a role in enhancing relevant and important signals so that we focus on relevant and important things.

Low-to-moderate concentrations of norepinephrine (NE) mediate these actions by acting preferentially on postsynaptic 𝛼2A-adrenoceptors. However, as the concentration of norepinephrine increases, norepinephrine begins stimulating 𝛼1 and 𝛽-adrenoceptors. Stimulation of 𝛼1-adrenoceptors and 𝛽-adrenoceptors (which occurs in high stress states) impairs our ability to focus.

When the NE concentration is too low, the signal strength (i.e., our ability to focus on things) is low. As the NE concentration increases so does the signal strength (i.e., our ability to focus on things) until it reaches a peak. Any additional increase in NE impairs, rather than enhances, our ability to focus. This explains the inverted U shaped curves depicted below.

Dopamine in the prefrontal cortex (PFC) plays a role in filtering out the irrelevant stimuli. That is, dopamine D1 receptors in the prefrontal cortex reduce the “noise” or irrelevant stimuli so that we can focus on relevant and important things without being distracted.

When DA levels are too low, all incoming signals, whether they are relevant or not, are treated in the same way. Therefore, it becomes difficult to focus on a single task as there are too many distracting stimuli. However, as the concentration of DA increases to moderate levels, it will decrease ‘noise’ by stimulating D1 receptors. This results in decreased firing of neurons to irrelevant inputs in PFC networks.

When DA levels are too high, D1 receptors in the prefrontal cortex are overstimulated and the brain’s ability to filter out the noise declines. Stressful situations and illicit drug use can cause dopamine levels to be too high.

Therefore, medications like amphetamines (Vyvanse, Adderall), methylphenidates (Ritalin, Concerta, Focalin), bupropion (Wellbutrin), and atomoxetine (Strattera) alter norepinephrine and/or dopamine levels to “enhance the signal” while “reducing the noise,” respectively.

Medications (or illicit drugs) that enhance dopamine too much in certain regions of the brain may cause us to “hyper focus” or “fixate” our attention on unproductive tasks. In addition, the euphoria and motivational reinforcement that results from overstimulation of dopamine receptors in the nucleus accumbens increases the risk for addiction and drug abuse.

In summary, we don’t want too much stimulation of dopamine (D1) receptors because this is associated with euphoria, hyper focus (like scrubbing the floor with a toothbrush), impaired attention, and drug addiction. We don’t want too little stimulation of dopamine (D1) receptors because this is associated with anhedonia, depression, lack of motivation, and apathy.

The same goes for norepinephrine. We don’t want too much norepinephrine because then we will feel symptoms associated with the fight or flight response such as anxiety, hypervigilance, racing heart, sweating, and shortness of breath. We don’t want too little norepinephrine because then we will feel symptoms like fatigue, depression, drowsiness, and weakness.

Therefore, we want our DA and NE to be not too hot and not too cold, but just right (yes, like Goldilocks). This is why controlled doses of stimulants can be very beneficial for some people. 

References

  1. Young, Joel. ADHD Grown Up: A Guide to Adolescent and Adult ADHD .(2007)
  2. Gil Zalsman & Tal Shilton (2016) Adult ADHD: A new disease?, International Journal of Psychiatry in Clinical Practice, 20:2, 70-76, DOI: 10.3109/13651501.2016.1149197
  3. Stewart, T. D., & Reed, M. B. (2015). Lifetime nonmedical use of prescription medications and socioeconomic status among young adults in the United States. The American journal of drug and alcohol abuse41(5), 458–464. doi:10.3109/00952990.2015.1060242
  4. Psychiatric Times. 7 Evidence-Based Insights About ADHDhttps://www.psychiatrictimes.com/adhd/7-evidence-based-insights-about-adhd
  5. Higgins, E.S. & George, M.S. The Neuroscience of Clinical Psychiatry: The Pathophysiology of Behavior and Mental Illness. 3rd Edition. 2018.
  6. Blumenfeld, Hal., MD, PhD. Neuroanatomy Through Clinical Cases. 2nd Edition. 2010.
  7. Sadock, Benjamin J., and Harold I. Kaplan. Kaplan & Sadock’s Synopsis of Psychiatry: Behavioral Sciences/clinical Psychiatry. 10th ed. Philadelphia: Wolter Kluwer/Lippincott Williams & Wilkins, 2007. Print.
  8. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Washington, D.C.: American Psychiatric Association, 2013. Print.
  9. Stahl’s Essential Psychopharmacology, 4th Edition. Cambridge University Press. 2013
  10. Schatzberg & Nemeroff. The American Psychiatric Association Publishing Textbook of Psychopharmacology. 5th Edition. 2017.

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