What is ADHD?
Attention Deficit Hyperactivity Disorder (ADHD) is a disorder of attention, concentration, impulsivity, and hyperactivity. ADHD happens to be one of the most heritable psychiatric disorders. Although ADHD was originally thought to be a disorder that only occurred 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 decrease in hyperactive-impulsive symptoms with age is likely related to the maturation of brain circuits in the cerebral cortex.
Symptoms of ADHD include inattention, hyperactivity, and impulsivity that impairs functioning. Below are some examples of symptoms common in ADHD:
- Inattention to detail, careless mistakes
- Often does not seem to listen when spoken to directly (e.g., mind seems to wander elsewhere).
- Doesn’t follow directions
- Difficulty organizing tasks and activities
- Often avoids tasks requiring sustained mental effort
- Often loses things
- Often easily distracted
- Often forgetful in daily activities
- Often has difficulty sustaining attention in tasks or play activities
- Often fidgets or squirms in seat
- Often leaves seat in situations when remaining seated is expected
- Often runs about or climbs in situations where it is inappropriate
- Often unable to play or engage in leisure activities quietly
- Internal restlessness, always on the go
- Often talks excessively
- Often finishes sentences or blurts out answers
- Often has difficulty waiting his or her turn
- Often interrupts or intrudes on others
What is Attention?
Attention is a cognitive function. Attention describes the mechanism that determines the importance of different stimuli and selects the one for the brain to focus on. Attention is an important component of our consciousness or awareness.
Which Brain Areas are Involved in Attention?
Although the distributed neural networks throughout the entire brain (especially frontal-parietal networks) contribute to most cognitive functions, there are some areas of the brain which appear to play a greater role in our ability to remain 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. The prefrontal cortex and cingulate cortex have especially important roles in working memory, which is described below.
So, What is Working Memory?
Working memory is what is actively being considered at any moment. For example, if someone gives you a phone number to call, your working memory is responsible for temporarily storing the number so you can dial it without writing it down. Working memory and attention are closely related and dependent on each other. Working memory and attention are important components of something we call executive functioning. The executive functions include working memory, attention, and other higher-level thinking skills such as organizing, planning, making decisions, and solving problems. We know a lot about the prefrontal cortex (PFC) thanks to the famous case of Phineas Gage (PG). PG was a railroad worker who had a tempering iron explode through his prefrontal cortex (and he lived!). He went from being responsible and organized to impulsive and inattentive. His personality also changed. We now know that trauma to the Prefrontal Cortex (PFC) impairs working memory.
Dopamine, Norepinephrine and Working Memory
Dopamine and norepinephrine appear to be two very important neurotransmitters involved in attention and working memory. This was demonstrated in rats and in monkeys. By measuring the amount of dopamine in that frontal region of the brain called the prefrontal cortex (PFC), investigators were able to demonstrate an inverse correlation between extracellular dopamine concentration in the prefrontal cortex and the number of errors during a delayed response task (such as the radial maze).
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.
The Nucleus accumbens (NAc) and Dopamine Transporter (DAT) density (huh?)
Attention and impulsivity are partially controlled by dopamine (DA) in the NAc. It makes sense that people are less distracted when pursuing activities they enjoy. Stimulant medications such as Ritalin, Adderall, and Vyvanse increase DA at the NAc and improve impulse control.
Interestingly, rats with damaged NAc become more impulsive and choose the immediate reward in impulse-control experiments. In young children, there appears to be a higher density of dopamine transporters (DAT) in specific areas of the brain responsible for impulsive behaviors. This would make sense because younger children are much more impulsive than adults (usually).
Not surprisingly, individuals with ADHD also have higher densities of dopamine transporters (DAT) in those same brain areas. As previously stated, higher DAT density has been correlated with more impulsive behavior. It turns out that patients with ADHD who have never been treated with medication have a slightly higher DAT density on average than those who have been treated with medication.
Changes in the prefrontal cortex (PFC) and striatum, a structure embedded in the subcortical white matter, 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 (see figure below).
Lastly, 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.
ADHD & Gender Differences
The symptoms of ADHD present slightly differently in males and females. A list of differences is provided in the table below.
|Onset at/after puberty||Onset before puberty|
|Less likely to be diagnosed||More likely to be diagnosed|
|Internalizing behaviors||Externalizing behaviors|
|Inattentiveness more difficult to identify||Inattentiveness easier to identify|
|Show distress by crying/sadness||Show distress through agitation|
|Impatience: complaints > action||Impatience: aggression/hostility|
|>comorbid conduct disorder or ODD
|>comorbid depressive/anxiety dxs||Higher rates of substance use dxs|
|Shyness/shame is common||Shyness/shame less common|
|More empathic||Often lacks empathy|
|Hormonal fluctuations can affect sxs|
Consequences of ADHD
Young adults diagnosed with ADHD are less likely to enroll in college or graduate from college. Students with ADHD are more likely to be on academic probation and have a lower grade point average. Adults with ADHD experience difficulties in all aspects related to employment.
Employment problems include poor job performance, lower occupational status, increased absence days, more workplace accidents and job instability. A World Health Organization survey estimated that 3.5% of all workers suffer from ADHD yet only a minority of these workers received treatment.
~20% of parents of children with ADHD have ADHD themselves (Faraone et al. 2000). Risky behaviors resulting in traffic tickets, motor vehicle accidents, and other injuries as well as substance use problems are more common in individuals with ADHD.
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). Other studies found that in the absence of comorbid conduct disorder, individuals with ADHD had no higher risk for later delinquency than adults with other childhood psychiatric disorders (Gjervan et al. 2012). This suggests that conduct disorder, and not ADHD symptomatology, likely explains the increased risk for delinquency in adulthood.
Reported Symptoms in Adults
Just like children, Adults with ADHD often present with hyperactivity, impulsivity, and inattentiveness. However, the manifestation of symptoms can be a bit different.
Hyperactivity: Inner restlessness, Talkativeness, Excessive fidgeting (lectures, movies, etc)
Impulsivity: Impatience (“acting/talking without thinking”), Difficulty keeping a job, Difficulty maintaining relationships, Attention seeking behavior
Inattentiveness: Feeling bored, Indecisive, Procrastination, Disorganization, Easily distracted
Other common complaints in adults with ADHD:
Mood swings, Difficulties dealing with stressful situations, Frequent irritability and frustration, Emotional excitability (anger over minor things), Relationship problems (short-lived, divorce), Coping with one or more children with ADHD
ADHD vs Bipolar Disorder
Differentiating ADHD from Bipolar Disorder can be difficult as many symptoms overlap. It doesn’t help that the two disorders often co-occur. Below is a table that might help differentiate the two.
|Signs/Symptoms||ADHD Alone||Bipolar Disorder Alone|
|Hyperactivity||If present, a constant problem||Appears only during mania|
|Mood swings||Rapid and brief||Sustained, lasts days to weeks|
|Difficulty with concentration||Constant problem||Intermittent problem|
|Euphoric moods||Not present||Present with mania|
|Delusions||Not present||May present with mania|
|Chronic irritability||Usually not present||Present|
|Frequently losing items||Common||Not common|
|Hallucinations||Not present||May occur with mania|
|Sleep Disturbances||Chronic periods of insomnia and/or hypersomnia||Insomnia common in mania|
|Disorganization||A key and persistent feature||Not common unless manic|
|Distractibility||A key and persistent feature||Not common unless manic|
|Grandiosity||Not present||Common, especially during mania|
|Self-Esteem||Usually poor||Inappropriately high during mania|
|Racing Thoughts||Often chronically present||Present, especially during mania|
|Impulsivity||Common feature||Present only during mania|
|High-risk behaviors||May Occur, but reason generally prevails||Present during mania, may be extreme and life-threatening|
Treatment Options For ADHD
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 without us even aware of it. In fact, only a very small percentage of brain activity contributes to our conscious awareness (about 15%).
The rest of the activity is all the unconscious processing, integrating, and analyzing of information that determines our behavior. In other words, a lot of the brain’s energy is spent “deciding” which signals are relevant and therefore require our attention. Think of all the activities we do that we aren’t even aware of. While walking down the street talking with a friend you probably don’t focus your attention on your left big toe–not unless your toe hurts or your friend is very boring! You aren’t aware of your left big toe because it is not important for what you are doing. It doesn’t mean the signals aren’t there–it just means we filter it out.
Imagine the brain is a piano. The actual piano itself can be thought of as the important neurons such as glutamate neurons and GABA neurons that play the basic melody (glutamate and GABA neurons make up the majority of the neurons in the mammalian brain).
Dopamine, serotonin, and norepinephrine neurons in the brain are fewer in number and act like the fine-tuners of the piano. That is, norepinephrine and dopamine (and many others including steroid hormones) are there to tighten the strings so the music sounds good. No one likes a song that is off beat or out of tune. Dopamine and norepinephrine are those “tuners” of the brain because they modulate communication between neurons. They help our brain decide what we should ignore and what we should focus on.
Interestingly, ignoring and focusing may be two separate processes or systems in the brain (but we will spare the nerdy details). Medications like amphetamines (Vyvanse, Adderall), methylphenidates (Ritalin, Concerta), bupropion (Wellbutrin), atomoxetine (Strattera), and others used in the treatment of ADHD work by enhancing these dopamine and norepinephrine “tuners” so we can better filter out the extra signals we don’t need and streamline the signals we do need.
Obviously the brain is much more complex than this but it gives us a theoretical framework for understanding how medications work. Medications (or illicit drugs) that enhance dopamine and norepinephrine too much in certain regions of the brain such as the nucleus accumbens (NAc) can be reinforcing and lead to abuse. Too much dopamine and norepinephrine may also cause us to “hyperfocus” or “fixate” our attention on things that might not yield a large reward at all (for example, scrubbing the floor with a toothbrush).
On the other hand, too little dopamine and norepinephrine in the same regions of the brain may cause us to lack motivation altogether or make us feel indifferent about doing anything because tasks don’t seem “worth it” enough (in other words, the expected reward isn’t perceived as being big enough). By modulating these brain areas with medications, we can tune our brains to the right frequency!
Psychostimulants include methylphenidates, amphetamines, modafinil, and armodafinil. Non-stimulants include atomoxetine (Strattera). The difference between stimulants and non-stimulants is somewhat arbitrary but has to do with the amount of “psycho-stimulation” a drug induces.
|Generic Name||Brand Name||Usual Starting Dose||Typical Daily Dose Range|
|Amphetamine-dextroamphetamine (Mixed Salts)||Adderall||5-10mg q4-5hrs||10-120mg|
|Adderall XR||10mg QAM|
|Lisdexamfetamine||Dexedrine spansules||5-15mg q6-8hrs||5-100mg|
|Long-acting MPH||Ritalin SR||20mg QAM||10-140mg|
|Ritalin LA||20mg QAM||20-120mg|
|Metadate CD||10-20mg QAM||10-120mg|
|Short-acting MPH||Methylphenidate||10mg q4hrs||10-140mg|
|Focalin XR||5-10mg QAM||10-80mg|
Both amphetamine (AMPH)and methylphenidate (MPH)target the dopamine and norepinephrine systems by increasing the concentration of these neurotransmitters. AMPH differs from MPH in that it promotes the release of dopamine and norepinephrine from the neuron by reversing the dopamine and norepinephrine transporters. Numerous studies have proven that stimulants are more effective than nonstimulants (atomoxetine) in treating the core symptoms of ADHD.
Prescription stimulants do not pose significant health risks to individuals when used as prescribed (Findling & Dogin, 1998). Side effects of prescription stimulants are dose-dependent, which means higher doses are more likely to cause side effects (Solanto, 2001, Weyandt et al., 2014). Psychosis, seizures, and heart problems such as fast heartbeat, high blood pressure, heart attacks, and sudden death are very rarely reported in individuals taking prescription stimulants by mouth at FDA-approved doses (Greenhill et al. 2002; Graham & Coghill 2008). While pre-existing heart disease is a relative contraindication, many patients with histories of heart problems can be safely treated with stimulants.
Both modafinil (Provigil) and Armodafinil (Nuvigil) are medications used to treat excessive daytime sleepiness in Narcolepsy. Both modafinil (Provigil) and Armodafinil (Nuvigil) promote histamine release throughout the brain, which increases wakefulness and arousal. Both of these medications have been used successfully in patients with ADHD.
|Generic Name||Brand Name||Usual Starting Dose||Typical Daily Dose Range|
Atamoxetine (Strattera): Strattera is a norepinephrine reuptake inhibitor.
Clonidine, Guanfacine: Clonidine and guanfacine are central alpha-2 agonists that modulate norepinephrine release. Clonidine is primarily a blood pressure medication but has been used successfully to treat the impulsivity seen in individuals with ADHD.
Bupropion (Wellbutrin):Bupropion is a norepinephrine and dopamine reuptake inhibitor similar to methylphenidate but does not increase dopamine and norepinephrine in the nucleus accumbens to the degree seen with traditional stimulants.
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