ADHD: “To Be or not to Be”

Angela Ine Frank-Briggs, from the Department of Pediatrics and Child Health, at the University of Harcourt Teaching Hospital in Port Harcourt, Nigeria, defines Attention deficit hyperactivity disorder, or ADHA, as a neurobehavioral developmental disorder, primarily characterized by the co-existence of attention problems and hyperactivity which effects about 3 to 5% of children worldwide, with symptoms starting before 7 years of age and in about 50% of cases continuing into adult hood. According to Briggs, in her article, Attention deficit hyperactivity disorder (ADHA), and to the American Academy of Child Adolescent Psychiatry, considers the following to be present before a child is to have ADHA: behaviors must continue for at least 6 months, and the symptoms must create a real handicap in a least two of the following areas of the child’s life: the classroom, on the playground, at home, in the community, or in social settings. Over the years, the terminology used to describe symptoms of ADHA has went thought many changes such as; “minimal brain damage”, “minimal brain dysfunction”, and learning/behavioral disabilities” just to name a few, according to the article. ADHA can be classified as a behavior disorder, a disruptive behavior disorder, oppositional defiant disorder, or a conduct, and antisocial disorder, suggests Briggs, ADHA has three subtypes. One is called a predominantly hyperactive-impulsive, symptoms include; hyperactive and impulsiveness. The second sub type is Inattentive type, in which, according to the article, the children are less likely to act out or have difficulties getting alone with other children, they may sit quietly, but they are not paying attention to what they are doing. The last subtype is a combination of the two, inattention and hyperactivity-impulsivity, called the Combined type.  To be diagnosed with Attention deficit hyperactivity disorder, symptoms must be observe in two different settings for six months or more, and to a degree greater than other children of the same age, according to Angela Briggs. The article states that a specific cause is not known, and even though some genes, like 7-repeat allele of DRD4 gene, play a role in ADHA, to date, no single gene has been shown to make a major contribution of ADHD.

Focus, Focus, Focus

I recently read the article “NEUROPHYSIOLOGICAL, PSYCHOLOGICAL, SPORT AND HEALTH DIMENSIONS OF THREE MEDITATION TECHNIQUES” written by Richard M. Buscombe.

The main thing that I found useful from this article was the description of several types of meditation.  There was breath based meditation, concentrative meditation, and mindfulness meditation.  I was particularly interested in the concentrative meditation, which involves developing a focus using a mental device, such as a mantra, body sensation, breath, or specific image.  Specifically, I was intrigued by Transcendental Meditation, which utilizes a mantra, which is a word or saying that is repeated in a rhythmic cycle.  I hypothesize that there could be a similarity between this form of meditation and addiction seeking behavior.  Addicts focus on one thing, which is their addiction.  Is it possible that this focus is similar to the focus on a mantra in meditation?

Additionally, there were some data collection techniques that might be useful.  Infiniti Thought Technology was a biofeedback system that could be used to measure blood volume, respiration rate, different brain waves, and muscle relaxation/tension.  I also liked how phenomenological data was analyzed using summaries that the participants had written.  I can do something similar to get an understanding of the addicts background and the reasoning behind the craving.

Gambling is not just a game

While reading the article “Compulsive features in behavioral addictions: the case of pathological gambling” written by Nadyel-Guebaly, I had several ideas for my research proposal, the biggest of which was to include gamblers as well as alcoholics.

Even though gambling is a behavioral addiction and alcoholism is a substance use disorder, they have many similarities.  I think it would be interesting to compare a behavioral addiction to a biologically based addiction because they are both addictions, just with different bases.  However, it might be hard to isolate gamblers from alcoholics because gambling often occurs with alcoholism.

One of the primary features of substance dependence is that “use is continued despite knowledge of having a persistent or recurrent physical or psychological problem.” Addicts compulsively use drugs without any thought of the consequences.  This is similar to pathological gamblers, who can have a hard time quitting gambling despite negative consequences such as losing all of their money.  These compulsive behaviors are associated with obsessive thoughts over the behaviors.  Both of these addictions are ego-syntonic, meaning they feel pleasure, gratification, or relief when they commit the act.  They cannot stop their addiction, because when they are in withdrawal they feel stress and anxiety which they want to get rid of.  The easiest way to not feel withdrawal symptoms is to not be in withdrawal anymore by taking the addictive substance or doing the addictive behavior.  Gamblers feels craving and withdrawal just like alcoholics do.

There are, according to Koob and Volkow, three stages of the addiction cycle: binge/intoxication, withdrawal/negative effect, preoccupation/anticipation (craving).  There are specific brain regions associated with each of these stages.  Binge/intoxication is associated with the ventral tegmental and ventral striatum.  Withdrawal/negative affect is associated with the extended amygdala.  Preoccupation/anticipation is associated with the orbitofrontal cortexdorsal striatum, prefrontal cortex, basolater amygdala, hippocampus, and insula.  It is this stage that I am particularly interested in.  I hypothesize that the preoccupation and anticipation of the addiction might be similar to having a mantra in meditation, which is related to increased pain tolerance.

For even more biology, there are different neurotransmitter systems that contribute to substance addiction and gambling.  Serotonin contributes to behavioral inhibition, and when it is suppressed the addicts feel a euphoric high.  Dopamine is related to learning, motivation, and salience of stimuli, including pleasureful rewards for enacting the addictive behavior.  Even though gambling is a behavioral addition and alcoholism is a substance use addiction, both of them effect the brain is a similar manner.

Loving the Pain

The article “What Imaging Teaches Us About Pain” by Elizabeth Church was very informative to me.

First, it describes pain.  As much as we may hate pain and avoid it at all costs, pain is actually a good thing.  It is “an alarm system that protects individual organisms from potential or actual physical threats.”  It is a complex sensory and emotional experience that warns us if there is potential or actual damage to us, or if something is just wrong.  One type of pain described is nociception, which is the activation of nerve endings that respond differently to tissue-damaging stimuli.  The activation of these nerve endings may or may not be perceived as pain.  Pain is actually a very subjective experience.  Our experience of pain is completely dependent on our interpretation of it.  It is colored by our belief about the pain, our expectations, and our mood.  Our perceptions may or may not match with the nociceptive input.  Basically, our pain is fueled by our mind.

However, biology comes into play as well with genetic factors that influence the experience of pain.  There are even specific neurotransmitters in the forebrain that are involved with the reduction of the intensity of the pain experience.  The pain matrix is a large network that becomes activated during the nociceptive processing.  What is interesting is that individuals have different portions of the central nervous system that play different roles in pain processing in this pain network.  To get into some hard biology, there are common regions of the brain that are involved in pain processing.  These include the sensory-discriminatory areas of the central nervous system, which are the parietal lobe of the cerebral cortex, including the primary somatosensory (sense of touch), secondary somatosensory, thalamus (relays sensory information), and posterior portions of the insula (linked to regulation of emotion and homeostasis, perception, motor control, self awareness, and cognitive functioning).  Also, areas of the brain associated with cognition and affect (anterior portions of the insula, the anterior cingulated cortex, and the prefrontal cortex) help regulate pain.

As far as I can see, a lot of pain processing is located in the brain.  This means that neural imaging can be used to show pain intensity in an objective manner versus the normal participant evaluations that are subjective to their experiences.  While an fMRI would be nice to use to an imaging tool, it seems a little bulky for my experimental design, so I think DOT diffuse optical tomography might work better.  The participant wears a helmet with lights sources and detectors that absorb and respond to light, and by some scientific magic  this detects changes in cerebral blood flow, which show areas of brain activity.  I think that this method will be a nice addition to the subjective VAS scale I intend to include in my experimental design.

Another interesting point of this article was that the best alternative (non-medication) treatment of pain is meditation.  Meditation overall can improve attention, relieve anxiety and depression, reduce anger and cortisol levels, and strengthen immune responses and gray matter density.  While the benefits of meditation are numerous, I could never get past the boring part myself.  Also, meditators had a lower pain sensitivity than control subjects.  When faced with heat, it took higher temperatures before they felt any pain!  The strength of this pain regulation depends on the amount of meditation experience, and unfortunately 2000 plus hours are needed for significant control of pain.  Short term meditation does have some effect, though.  I would love to contrast a meditator with a drug addict, because in a way addicts adhere to their own inner mantra.

Bells and Drool: A Way to Classically Relieve Pain

I think that the article “Classical conditioning and pain: Conditioned analgesia and hyperalgesia” written by G.Miguez might be useful for my research proposal.

This article describes how reaction to pain can actually be conditioned, or trained.  It uses the theory of classical conditioning, which was first described by Pavlov in his famous dog and bell experiment.  An unconditioned stimulus, such as food, causes an unconditioned response, such as drooling in dogs.  If a conditioned stimulus, such as the ringing of a bell, is paired with an unconditioned stimulus, then eventually the conditioned stimulus on its own will cause a conditioned response.  In this case, the ringing of a bell will cause the dog to drool even though there is no biological reason for a dog to drool at the ringing of a bell.

This is important for the regulation of pain sensitivity.  In humans, several types of stressors (unconditioned stimulus) result in an increased tolerance to pain (unconditioned response).  These stressors include, well, stress.  One example is intense physical activity (think of marathon runners who continue to run and soldiers who do not realize that they are wounded).  In animals, even a novel situation can cause a reduction in pain levels.  In humans, other stressors that result in reduced pain are loud noises, thermal stimulation, footshocks, and solving mental arithmetic problems and challenging memory tests.  So math is good for something at least.

If an initially neutral stimulus is paired with one of these stressors, it could reduce pain by acting as a conditioned stimulus.  The conditioned stimulus can be something in the environment.  However, it is important to note that not all stressors make changes in pain sensitivity in the same direction.  Some will cause less pain to be felt, others more.

As a way to relieve stress and escape from the struggles of everyday life, it is very possible that the substances of addiction are conditioned stimulus that have analgesic (pain relieving) properties.  Withdrawal comes with very negative side effects and makes those trying to quit feel miserable.  If an alcoholic who is craving a drink gives in to the temptation, he will be blissfully relieved of his withdrawal symptoms, even if it is only for a short time.  Therefore, I think it is reasonable to hypothesize that the substance becomes associated with feeling good and pain-free, and becomes a conditioned stimulus.  Maybe even the thought of the conditioned stimulus might have analgesic properties.

A Cold, Painful Task

I recently read “Effect of Brief Mindfulness Intervention on Tolerance and Distress of Pain Induced by Cold-Pressor Task” written by Xinghua Liu.

This article tested short term mindfulness meditation against distraction intervention on pain tolerance and pain intensity.  The mindfulness intervention included increasing awareness to bodily sensations and objectively accepting these experiences.  Mindfulness is accepting the pain rather than avoiding or fighting it.  The distraction intervention, which in most studies is completing hard math problems, was imagining a happy scene.  A distraction from the pain can lessen it.  Surprisingly, there was no significant difference in pain tolerance and intensity between subjects who used the mindfulness method and those who used the distraction method.  I was worried that, because mindfulness is negatively correlated with cravings and addiction and it is positively correlated with increased pain tolerance, addicts, who are not naturally mindful, will have a decreased pain tolerance.  This article shows, however, that there are different ways to tolerate pain, distraction being just as effective as mindfulness.  Even if the guided imaginings of the addicts are nothing like the process of meditation, I am interested to see if the repeated thought process involving addictions is similar to the distraction technique.  It might be good to have a control group that uses the distraction technique in my project.

Additionally, I think I will use the Cold pressor test mentioned in this article to measure pain.  The equipment is two plastic containers.  One is filled with warm water that is 37 degrees Celsius and the other with cold water and ice that is kept around 2 degrees Celsius.  To prevent the participants’ hands from touching the ice directly, the ice is wrapped in plastic and tucked away in a bottom corner of the container.  First, the participants place one of their hands in the warm container for two minutes to establish a baseline temperature.  Next, the participants move that same hand to the container that is cold.  They simply keep their hand in the water until they cannot handle the pain anymore, in which case they remove their hand from the water.  To prevent any damage to the hand, the maximum time limit is 5 minutes, but the participants are not told this.  Immediately after the procedure, the participants rate their pain experience.  This seems like a simple and effective design, and an overall good way to test what I am trying to measure.

Craving a Fix

I recently read the article “Cognitive and affective mechanisms linking trait mindfulness to craving among individuals in addiction recovery”  by E.L. Garland that I think I can use in my research proposal.

The article is about how mindfulness is related to craving.  Craving is the subjective experience of physical data related to the withdrawal from the cue (alcohol, drugs, etc.).  More than just the physiological experiences, craving is the inner interpretation of those experiences.  It is the constant thought of the craved substance, the anticipation of how good it will feel when the addict finally gets the substance, and all of the thoughts and behaviors that drive individuals to acquire the substance no matter what the cost.  I want to utilize this behavior in addicts to see if they are so focused in their cravings that they ignore reality, in the form of ignoring pain.  I wonder if their need for a fix is so great that other perceptions do not even register in their minds.  I feel like this repetitive, central goal might be somewhat similar to meditation that involves repeating a mantra, so I will have to read more on meditation.  Meditation could be a good contrast against addictions, since it is viewed in a positive light rather than a negative one and has already been shown to increase pain tolerance.

In this study, craving was measured using the Penn Alcohol Craving Scale.  It measures the duration, frequency, and intensity of craving for alcohol on a 7 point scale  with questions such as “How often have you thought about drinking or how good a drink would make you feel.”  This is perfectly designed to test the craving levels of the alcoholics in my proposal.  Since the scale was modified in the article to also measure cravings for drugs, I think it would be reasonable for me to modify the scale to measure the cravings of pathological gamblers.  This way, I would be able to compare the levels of craving of the addicted participants to their performance in the pain test.

 

A Guided Path Through Pain

The most important piece of information I gleamed from HC Fox’s article “Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues” was the use of guided imagery.  Guided imagery involves “re-living” a recent stressful or drug-related personal event through guided imagery and recall.  I feel like this would be a good way to have the addicts in my study focus on their addiction before the pain test.  Instead of just telling the addicts to think of their addiction, this method would be standardized and repeatable, meaning the participants would all be told to imagine the same scenario.  It might be how they felt when they last indulged in their addiction, or imagining a scenario where they can indulge in their addiction all they want with no consequences.  I want to try and mimic the obsession that comes with intense addiction, and focusing in this manner might work.

Also, I liked the statistic analyses that were performed.  A linear mixed effect model is good when there are repeated measurements from the same individual.  This could be good if I have the participants do the pain test with and without the independent variable.  A T-test was performed, which is good to determine demographic and baseline drug differences.  Both of these statistical models could be used in my study.

Pain Sensitivity in Opiate Addicts

I recently read the article “Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving” written by Ren Zhen-Yu.  This article is a great foundation for what I want to write my research proposal on.

In the article, the different intensities of cravings of opiate addicts was related with how much pain was felt.  Overall, the opiate addicts  in this study showed a shorter tolerance for pain than control subjects, which is one of the reasons I have decided to use alcoholics instead of opiate addicts in my study.  Opiate addicts can show either an increased tolerance to pain or a decreased tolerance to pain, depending on what stage of addiction the individual is in-development, maintenance, withdrawal periods, and periods of abstinence.  This could be because opiates have a specific receptor in the brain, since our bodies can actually produce certain opiates (endorphins).  Also, opiates such as morphine are used to treat pain directly.  Additionally, people who are at risk for opiate addiction might already be partially intolerant of pain.  They might choose to take opiates to relieve their pain.  Our bodies cannot naturally produce alcohol, and alcohol does not directly affect pain receptors, so I feel like alcoholism will be a better substance disorder for me to test than opiate addiction.

I like the descriptions of the participants that were involved in the study.  The opiate addicted participants had to be four months sober, could not be on any other psychoactive drugs except nicotine (so cigarettes are okay), any prescribed medicine, any medication for physical or mental disorders, and could not have a pain condition.  The control patients had to have no history of substance abuse, pain conditions, serious physical or mental disorders, and not be on medication.  To ensure this, a urine sample was taken to test for drugs.  They were collected through word of mouth and advertisement.  I feel like this will be a good model for me to follow.

A Cold pressor test (CPT) was used to test for tolerance to pain and pain intensity (sensory aspect) and distress (affective/emotional aspect).  I really like this quote that was used to describe the difference between pain intensity and distress. “To understand the difference between pain intensity and distress, think of listening to music on a radio. As I turn the volume up, I can ask you how loud the music is or I can ask you how pleasant or unpleasant the music is to listen to.  The intensity of pain is like the loudness of music. How pleasant or unpleasant the music is depends on how much you like or dislike the music, and the distress of pain depends on how much you dislike the sensation.”  These levels were measure using separate visual analogue scales VAS 0-100, 0 being “not at all intense” or “not at all unpleasant” and 100 being “the most intense pain imaginable” or “the most unpleasant pain imaginable.”  Again, this seems like a really good model for me to follow.

 

ADHA: Liability or Assett?

Considering the social context of ADHA, could ADHA be an asset or a liability? Dan Eisenberg, PhD, and Benjamin Campbell in their article, The Evolution of ADHD: Social Context Matters, ask a very good question to begin with: Why hasn’t natural section removed the genes that underlie ADHA from the human population? According to Eisenberg and Campbell, we must consider our current and past social environments over our evolutionary history, along with genetic and molecular evidence.  Humans today live in a very different environment than our hunter-gatherer ancestors did over 10,000 year ago. According to the article, learning took place through play, observation, and informal instruction, rather than a structured classroom almost all of us have experienced today.  The genetics of AHDA plays a key role as well. It turns out that the 7R (ADHD associated) allele of the DRD4 gene was created around 45,000 years ago and was selected for, referring back to the article, and therefore likely was evolutionarily advantageous. In a study conducted by Chuansheng Chen and colleagues, according to the article, populations with longer histories of migrating tended to have a greater frequency of DRD4 7R alleles. Later, the article goes on to say, that Chen and his colleagues reported that populations that currently practiced a nomadic lifestyle tend to have higher frequencies of 7r (ADHD-associated) allele than sedentary populations. The article states that they analyzed the DRD4 genotypes of 150 adult Ariaal men, half form nomadic groups and half form the settled groups. The nomadic men who had the 7R ADHD associated allele were less underweight than the nomadic men, but among the settled man, the reverse was true. Clearly, according to the article, something about the nomadic context that allows people with ADHA­ like behaviors to be more successful in an evolutionary sense. The article ends with a question, more or less: Are there areas in our society where children and adults with ADHD might better use their traits? And on a finally last note, children and adults are lead to believe that this is disability, but as it turns out, depending of social context, could be seen as strength.