2016 HDSA Convention Summary Article
Strategies for Managing Depression in HD Families
Presentation Title: Strategies for Managing Depression
June 3, 2016
Presenter:
Dr. Karen Anderson, MD — Director of the HDSA Center of Excellence at Georgetown Hospital in Washington, D.C. and psychiatrist specializing in neuropsychiatry.
Panelists: Doris, Anne, and Cary — caretakers and members of the HD community who have been affected by depression.
- Background
The 2016 Annual Convention of the Huntington’s Disease Society of America (HDSA) took place in Baltimore, Maryland, from June 2–4, 2016. The HDSA Convention is the largest Huntington’s disease (HD) convention in the world and covers a combination of education, advocacy and research topics over the course of three days.
The purpose of this article is to summarize “Strategies for Managing Depression”, a presentation given at the 2016 HDSA Convention. To read more about the relationship between HD and depression, please visit this site.
This article will summarize the main points given in the presentation. It lasted a little over an hour, with 30 minutes allocated to Dr. Anderson’s presentation, 30 minutes for a panel on HD and depression, and 10 minutes for questions.
- Dr. Anderson’s Presentation (30 minutes)
Dr. Karen Anderson practices neuropsychiatry and is the director of the HDSA Center of Excellence at MedStar Georgetown University Hospital. At the start of her talk, Dr. Anderson disclosed that she has worked as a consultant and scientific advisor for Lundbeck and Teva pharmaceutical companies. She also stated that she has acted as a site investigator for several of their clinical trials, including SD809, a drug used for the treatment of chorea and referenced in this presentation. She was also on several scientific advisory panels for both pharmaceutical companies.
Dr. Anderson emphasized that the goal of her talk is to share information, not to give personal medical advice. The information should not be taken as a sole source of medical advice; instead, it should be discussed with one’s care team and clinicians.
Introduction and Symptoms of Depression in HD
In this section of the presentation, Dr. Anderson gave an overview of the relationship between depression and HD.
Causes and prevalence of depression in people with HD
Huntington’s disease affects the brain’s neurochemistry, which can lead to depression. Another factor that contributes to depression in HD patients is the loss of ability to do everyday things, such as driving, working, taking care of children, being independent, and maintaining continence. Losing the ability to do things once central to the identity of someone diagnosed with HD can often trigger depression. The recent loss of a loved one to HD or the anniversary of their death is also a common cause of depression. Additionally, the end of a treatment study can precipitate depression in study participants. For many people, the end of a clinical trial can represent the end of feeling proactive, and it is often unknown whether or not the trial made a difference in the progression of their disease. Centers doing clinical trials can mitigate this by staying in touch with patient participants and making sure participants are thanked and made aware of the impact they have made on HD research.
Many people experience depression and there are many reasons why someone, with or without HD, might experience depression. There are also several treatment options that have proven successful for HD patients who experience varying degrees of depression. As such, one of the last sections in this article focuses on treatment strategies such as psychotherapies, talk therapies, and medications.
In the brain, chemicals involved in reward, pleasure, and mood are affected by the progression of HD pathology. Depression can occur across all stages of HD, and even before someone starts experiencing motor control symptoms. Studies estimate that 20% to 80% of HD patients have depression at some point during their illness.
Depression often occurs in the early stages of HD. It can be concerning when someone in an HD family becomes depressed, since this is often thought to be a first sign of HD. Dr. Anderson advises her patients to seek treatment for depression when they are worried that it might be an early sign of HD. For someone at risk for HD, being treated for depression does not mean they will be diagnosed with HD.
Impact of depression on HD
Depression can have an impact on the progression of HD, which is a compelling reason to seek treatment. In fact, across neurological diseases, people who are depressed are found to have more negative outcomes. HD often progresses faster in people who are depressed. For example, depressed HD patients may experience greater memory decline, an inability to organize thoughts, lower quality of life, and decreased ability to care for oneself.
For people with HD and depression, the depression may worsen as the condition progresses. People can develop depression as they become aware of early symptoms of HD. Dr. Anderson reiterated that depression can worsen as patients start to lose the ability to perform everyday activities, or are told that they need to change how they perform certain activities in response to HD. Dr. Anderson expressed the importance of being aware of depression across all stages of HD.
Symptoms of Depression
Dr. Anderson outlined how she evaluates whether someone has depression. Psychiatrists ask about the following factors:
- Appetite changes
- Low mood, tearfulness
- Hopelessness
- Poor concentration
- Sleep changes
- Low energy
- Fatigue
- Feelings of guilt
- Loss of interest in activities
- Loss of enjoyment
It is important to note that depression does not always manifest itself as sadness. It can appear as irritability, anger, anxiety, rumination, or resentment of caregivers. Depression can also take the form of a personality change.
A lot of people with HD experience sleep problems such as a flipped or erratic sleep schedule. They may also experience sleep fragmentation—this occurs when people sleep for a normal amount of time, but not well. Being fatigued can contribute to a low mood and a less cognitively aware state. For this reason, psychiatrists often look for underlying sleep issues that worsen depression symptoms.
Depression versus Apathy
Families and clinicians may confuse depression with apathy. About 50% of HD patients struggle with apathy or a general lack of motivation. Dr. Anderson expressed that the difference between depression and apathy matters because they require different treatment approaches. Depression can be treated with a combination of structured activity and medication. Apathy can be addressed with exercise and structured activity, but is harder to treat with medication.
It is also important to talk about apathy in order to educate families with HD. When someone has apathy, it’s hard for them to get started with an activity and they are less likely to be interested in doing things. Someone with apathy is not being stubborn. In fact, having a hard time with motivation is often a part of having HD.
Apathy can look like depression and sometimes there can be a combination of the two. Working with a psychiatrist can help tease out whether someone is experiencing depression, apathy, or a mix of both. Dr. Anderson noted that some antidepressants, such as SSRIs, are known to make apathy worse. A reduced dose or tapering off the antidepressant can sometimes help with this.
Non-pharmacological treatment strategies
Depression is very treatable, with or without drugs. Dr. Anderson emphasized that effective non-drug treatments are available. Some people do not respond to or tolerate antidepressants. They may experience side effects or may be unwilling to add another medication to their existing pill regimen. Some people might want to try counseling, either alone or in conjunction with medications.
If someone seems depressed, Dr. Anderson suggests increasing their activities and providing structure to their day. If exercise is a possibility, being physically active has been shown as helpful for mental health in general. Even a bit of walking or seated exercises with hand weights can alleviate depression.
In addition, if someone has lost a hobby due to HD, it can be helpful to re-frame hobbies in ways that the person is able to do. It is useful to consider how they can reclaim that activity. For example, if someone used to enjoy open water fishing, it is possible that they could try to fish while sitting on a platform.
Outdoor time is recommended to help with depression. Daylight exposure helps reset one’s internal clock and improves one’s mood. If it is not possible to be outside, sitting in a sunny room or getting out on the patio can make a difference.
Simply talking to someone supportive can alleviate depression. Supportive talk therapy can be helpful to address depression, isolation, or feelings of dependency, but the individual providing supportive conversation need not be an expert in HD. One type of therapy is called cognitive behavioral therapy. Patients are taught to catch negative feelings, then label and re-evaluate them. This type of therapy is practical, goal-oriented, and occurs over a few months.
To help with irritability, it is important to consider food intake. If a loved one is moody or cranky, it often helps to look at how much they are eating. People with HD need more calories than the average adult. If blood sugar gets too low, mood drops. Someone who is home by themselves should have a friend knock or call to remind them to have a snack and keep their blood sugar stable.
Lastly, Dr. Anderson talked about mindfulness as a way to cope with depression. Mindfulness is the process of paying attention on purpose, and without judgment, to the present moment. The goal is to reduce physical and emotional stress to make day-to-day life better. Being mindful involves being aware of experiences, rather than being consumed by them. Dr. Anderson discussed how mindfulness can help people make more purposeful choices instead of reacting automatically to things they cannot control. For example, at a family Thanksgiving that might be stressful or unpleasant, you can use mindfulness to ask yourself how you will experience the dinner in the best way possible.
Medication treatments for depression
Dr. Anderson talked about the different medication treatments for depression. As a psychiatrist, she considers potential side effects when deciding on a treatment course for each patient. The choice of treatment depends on the side effect profile for a particular individual.
When treating someone’s depression with medication, it’s important to keep in mind that the response to treatment is not always steady and is almost never immediate. Someone may get a bit better but then it may take more time to see further improvement.
Dr. Anderson provided the following list of antidepressants with reference to their side effects:
- Selective serotonin reuptake inhibitors (SSRIs). Options vary from more activating (such as paroxetine, fluoxetine, citalopram) to less sedating (sertraline).
- Vilazodone- SSRI and a 5-HT1A (serotonin) receptor partial agonist. This drug is thought to reduce sexual side effects.
- Serotonin–norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine. This class of drugs works well to treat anxiety, but they have cognitive effects and can cause people to feel tired and lethargic. If someone gets through initial treatment with these, they often do very well. But for someone concerned with how this might affect their thinking, this might not be the best drug to start with.
- This drug is activating and may worsen irritability, anxiety, and insomnia.
- This drug has noradrenergic and serotonergic activity. This drug is sedating and increases appetite. It is a good choice for someone who has trouble sleeping and gaining weight.
- These drugs have cognitive effects. People can feel lethargic or sedated, and they may gain weight.
Dr. Anderson discussed the concept of augmenting, or adding another drug (such as another antidepressant or mood stabilizer) to help the initial antidepressant work better. This can be done if the antidepressant is no longer working as well, or if it works well but not completely. Adding a drug from another class is preferable to increasing the dose of antidepressant, which might have side effects.
With antidepressants, patients take a pill for 4 to 6 weeks and often only start to feel a noticeable improvement about a month or more after starting to take the medication. It is often difficult to take a pill for a month or more before feeling a positive effect. Because the antidepressant has to be taken regularly, it is important to support people and encourage them to keep taking the medication until they feel better. In addition, when people start to feel better, they should keep taking the medication for 9 months or up to a year. If they stop too early, they could have a relapse, meaning the depression could come back and it could be harder to treat the second time. Some patients with a history of severe depression stay on medications more long-term.
Dr. Anderson made an important point about a drug called tetrabenazine (TBZ), used to treat chorea in HD patients. TBZ interferes with dopamine, serotonin, and norepinephrine in the brain. These important chemicals help us to be interested, have a good mood, and be engaged in life. They may appear at lower levels when someone is depressed. If depression or suicidal thinking occurs, TBZ should be reduced as it works by interfering with the very chemicals that naturally prevent depression.
Suicide
In the HD community, suicide is a very important topic to talk about openly because people with HD are at greater risk of taking their own lives. It is estimated that suicide risk increases 4 to 7 times among HD patients compared to the rate of suicide in the general population. Changes in the brain can make people with HD more impulsive, which is a risk factor for suicide.
Dr. Anderson advised families to employ a strategy called “means reduction”, a way of reducing opportunities for impulsive attempts to commit self-harm. For example, gun owners can keep guns and bullets separated and locked up, or guns can be removed from the home altogether. In addition, family members can manage medications and only dispense daily doses.
For more information on suicidality in the HD community, please visit this site.
The presentation closed with a reiteration of how important it is to talk about depression is in the HD community, since the simple act of talking is a step towards helping people cope with depression.
- Panel with members of the HD community speaking about their experiences with depression (30 minutes)
Next, Dr. Anderson facilitated a panel discussion with Doris, Anne, and Cary, three women who spoke openly about their personal experiences with depression and HD. Dr. Anderson asked a series of questions listed below:
Question 1: What is it like when someone you love is depressed? How can you tell?
According to the panelists, when someone has depression, they often don’t want to get out of bed. If the caretaker is not there to get them out of the house, they may stay in bed all afternoon. They may feel a lack of motivation, energy, and initiative. In addition, they may talk less and appear more withdrawn.
Question 2: Have you tried any of the non-medication treatment strategies I discussed? Which ones have worked well for you?
Having an activity, a structured schedule, or something to look forward to makes a big difference! Walking or mild exercise improves mood.
Question 3: What do you do when someone is at work and can’t be there to provide structured activity?
That is definitely a difficult situation, and it is hard to have a good answer- it depends on the individual circumstance. Overall, finding small ways to make the person feel less stuck should be the priority. For example, engaging with their network of family, friends, and former coworkers could be helpful. Seeing people for coffee or lunch once a month can provide support.
Question 4: What have your experiences with antidepressants been like? How do you know if they are working? What does it look like when someone gets better from depression?
When someone is getting better from depression, they may start to seem more like their old self- for example, they may talk more, seem more energetic, or be more motivated to do activities.
Question 5: Have you found that people get better from depression slowly or not?
Based on the experiences of the panelists, it has been a slow and gradual improvement.
Question 6: Have there been setbacks or ups and downs when someone is getting better from depression?
Certainly with the disease in general, there are ups and downs.
Question 7: In your experience, what’s the difference between being depressed versus being discouraged by having this disease that affects so many different things?
People with Huntington’s disease can feel discouraged and sad, but depression is persistent and chronic. One of the panelists, when discussing her son who has HD, said: “There’s a sadness, but I don’t see the depression in him. He keeps going.” Another panelist added: “Projecting into the future makes everything hard- it’s a waste of energy. I have found that cognitive behavioral therapy helps. Catastrophizing your life does not go anywhere. It’s more practical to try and move your thought to a positive direction. But it took me 10 years to get to this point.”
A third panelist shared a thought brimming with hope: “I’m sixty now, long lived for an HD person. That makes me feel better.”
Resources and further reading
The recording of Dr. Anderson’s presentation: http://hdsa.org/about-hdsa/annual-convention/2016-convention/
Dr. Anderson’s presentation slides: http://hdsa.org/wp-content/uploads/2016/06/HDSA-2016-Anderson-Depression-Strategies-June-3rd.pdf
National 24/7 suicide hotlines:
1-800-273-TALK (8255)
1-800-SUICIDE
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2016 HDSA Convention Summary Article
Educating Law Enforcement and Medical First Responders on HD
Presentation Title: Effective Strategies for Educating Law Enforcement and Medical First Responders on HD
June 3, 2016
Presenters:
Doug Schulte — member of the HD community living in California and working to educate law enforcement on Huntington’s disease.
Morgan McLane — member of the HD community living in Western Pennsylvania who is involved with fundraising for Huntington’s disease research.
Officer David Coleman — law enforcement officer in Pittsburgh, Pennsylvania who attended an HD support group meeting prior to this presentation.
- Background
The 2016 Annual Convention of the Huntington’s Disease Society of America (HDSA) took place in Baltimore, Maryland, from June 2 through June 4, 2016. The HDSA Convention is the largest Huntington’s disease convention in the world. It combines education, advocacy, and research in three days of learning for the Huntington’s disease community.
One of the presentations given at the 2016 convention was entitled “Effective Strategies for Educating Law Enforcement and Medical First Responders on HD”. This article will summarize the main points given in the presentation. It lasted a little over an hour, with 30 minutes allocated to Doug’s presentation, 30 minutes for Morgan and Officer Coleman to speak, and 10 minutes for questions.
- Presentation Part I: Doug Schulte (30 minutes)
1. Introduction
As a caregiver to his wife, Doug is active in San Diego’s HD community. He spoke about the work he has done to educate law enforcement on HD in his county. In the city of San Diego, Doug has given over 30 presentations and educated over 1,000 law enforcement members. His goal in this presentation is to give an overview of the work he has done in order to give audience members a roadmap on how to educate law enforcement in their communities.
During his talk, Doug references mental health as it relates to HD and law enforcement. From a law enforcement perspective, the behavioral symptoms of HD appear similar to those of mental illnesses. As such, the educational resources on HD made available to members of law enforcement fall under the same category as resources describing other neurodegenerative and mental health conditions.
Doug began by sharing the story of his involvement with the HD community. In addition to caring for his wife, who is in the advanced stages of HD, Doug attends support groups and fundraising events in San Diego. He has had first-hand experience with law enforcement officers who are largely unaware of HD and misinterpret the situation as someone being under the influence or intentionally uncooperative. These officers are insensitive to the fact that HD symptoms can often mirror those of individuals under the influence of drugs or alcohol or those of individuals living with different forms of mental illness. Because of these negative interactions, Doug is driven to help HD families avoid unnecessary altercations with the police by educating law enforcement on HD.
Doug’s ultimate goal is that first responders, the medical community, and the HD community can work together to support families with HD.
2. Explanation of Doug’s efforts to educate officers in San Diego
Doug described the efforts made in San Diego County to educate law enforcement on HD. In the last 5 years, Doug claimed that the number of mental health incidents that law enforcement responded to doubled, indicating the increasing importance of educating law enforcement in San Diego on HD.
To begin educating law enforcement in San Diego on HD, Doug contacted the Psychiatric Emergency Response Team (PERT). Teams such as PERT exist in all major counties nationwide and consist of specially trained officers paired with licensed mental health professionals. PERT provides clinical support, education, and training to law enforcement for dispatch calls involving persons with mental health crises. They aim to provide appropriate crisis resolution by connecting people to the least restrictive level of care. This can help prevent unnecessary incarceration or hospitalization. PERT is a source of communication between law enforcement and the mental health system of care.
Importantly, PERT also provides education and training to law enforcement members on mental health issues. This is where Doug saw the potential for education on Huntington’s disease. Members of law enforcement attend PERT academy, where they undergo a 3-day intensive training. Doug assembled a team of HDSA members to present to PERT supervisors, clinicians, and PERT academy officers about how to incorporate HD into their current law enforcement curriculum. The HDSA presentation was well received.
Since then, Doug’s team has given classes on mental health training to smaller agencies as well. In his opinion, the relationship with PERT has helped spread the word and is the foundation of his strategy’s success. Doug’s take-home message was that contacting one’s local PERT or PERT-equivalent is a great way to start educating officers on HD.
It is important to note that law enforcement officers are only required to receive 12 hours of mental health training and thus rely heavily on teams like PERT. Doug argues that system-wide change is needed in order for these officers to receive a more comprehensive education on mental health with the goal of training officers that are more compassionate and helpful towards people with HD.
Other beneficial resources that exist in San Diego County include:
- The Resource Access Program (RAP), a pilot program to train paramedics on how to respond appropriately to frequent 911 users (such as some HD families). Resources like RAP are emerging in metropolitan centers across the United States.
- The Take Me Home Program is a regional online photo-based information system hosted by the San Diego Sheriff’s Department. It is accessible online to all law enforcement in the county and assists them during contact with members of the community who have conditions including HD, autism, dementia, Alzheimer’s, and Down syndrome. Through this program, people can register the specifics of their condition along with a photo and emergency contact information. It is important to note that this program only works if families enter their information, making it important for members of the HD community to actively seek out these tools.
Doug also mentioned the potential for educating paramedics about HD since they are already required to receive continuing education four times a year to get refreshed on advanced life support skills and recent protocol changes. Other agencies like the fire department do refresher trainings, which could be another potential channel through which to spread HD awareness.
3. Advice for presenting to law enforcement officers
Doug presented a number of tips for giving successful presentations to law enforcement groups:
- Personalized PowerPoint presentations are more effective.
- If the presenter has a personal connection to HD, include personal anecdotes, particularly any stories involving law enforcement officers, to give audience members a better understanding of the disease and its connection to the profession.
- Share information about the behavioral symptoms of HD that have the potential to increase the frequency of interactions with law enforcement, such as impulse control or memory impairment. For example, the presenter could share that one of the behavioral symptoms of HD is shoplifting. Because Huntington’s disease impairs memory and attention span, the person may forget to pay for an item before leaving with it. It is crucial for law enforcement to understand that people with HD are usually not intentionally stealing. The disease has taken away their ability to control impulses.
- Include possible solutions and reference where past successes have occurred.
- Provide video documentation of the presentation for continued reference as well as additional online resources.
4. Understanding the 911 system
Doug finished his talk by discussing the 911 system and the resources used by individuals charged with responding to calls. On average, 40% of San Diego residents have called 911, but this number is much higher for members of the HD community, especially among people who have fallen or who display difficult behavioral symptoms.
When sharing the true story of an HD family in San Diego whose middle-aged son began displaying difficult behavioral symptoms, Doug described the overly aggressive approach taken by the local law enforcement members involved. Rather than being sensitive to HD symptoms, eight officers arrived at the home of this family with rifles and canine units. This was a traumatizing event for the family and likely could have been avoided if the 911 caller had given more information to the dispatcher about their son’s HD diagnosis.
The second time that the family called 911, they were better informed thanks to resources from a support group, and specifically requested the PERT team. This time, three calm law enforcement officers came to the home. Seeing that the family was visibly upset, the officers assured them that they would take care of their son and would not hurt him. Next, the police officers did something crucial: they called for a medic response. Paramedics arrived, and the son was taken to an emergency room with a psychiatric department and given medications to help with his behavioral symptoms. This story shows that a clear line of communication between HD families and law enforcement representatives is crucial.
When on the phone with 911 dispatchers, Doug advises that HD families give clear, specific descriptions of the situation, and mention the influence of Huntington’s disease. If HD is mentioned on the phone, resources like the Resource Access Program may respond to the call. If the officer arriving at the scene has specific information, they are more likely to adopt an understanding and helpful approach to the situation.
Doug finished his segment of the talk by explaining that law enforcement agencies are actively looking for opportunities to educate their officers about HD and that the HDSA presentation he has used with officers in San Diego is a successful way to achieve improved understanding of HD among law enforcement officials.
- Presentation Part II: Morgan McLane and Officer Coleman (30 minutes)
Morgan McLane is active in the HD community in Western Pennsylvania. He co-founded Barbara Lee’s Fast Track to a Cure for Huntington’s disease, a fundraiser that has raised over $110,000 from 2006 to 2016. Morgan was inspired to educate police departments about HD when he heard the story of Dr. Tomasi, a man with HD who was detained overnight by police who believed he was intoxicated.
Officer Dave Coleman has worked in law enforcement for several years and has been a full-time police officer in Pittsburgh, Pennsylvania for three years. Dave and Morgan work together to educate law enforcement on HD in his area.
According to Officer Coleman, working in small-town law enforcement confers many benefits that can help families with HD. For example, HD families can benefit from knowing local officers and command staff when a crisis occurs. In a small town, officers can work with citizens to develop a plan or strategy in the event of a crisis and often have better documentation of what to expect in certain HD households. In his words: “The more we know going into a situation, the better.”
After a series of questions, the presentation closed with a reiteration of how education and communication between law enforcement and the HD community can lead to an effective and mutually beneficial relationship.
- Resources referenced in this presentation and made available by HDSA:
– The law enforcement toolkit, which includes a thumb drive containing a PowerPoint presentation used to educate law enforcement on HD. This toolkit can be used by members of the HD community to educate law enforcement in their local area.
– The Caregiver Toolkit for interacting with law enforcement. This toolkit is a resource for families. It explains how to handle the behavioral symptoms of HD, and provides suggestions for interacting with law enforcement.
– The HD profile card, which is carried with the person who has HD. It can be given to law enforcement to bring them up to speed.
– The medical bracelet, standardized by HDSA. Most medical bracelets have the name of the condition, such as “diabetes”. The HDSA-standardized bracelet contains the patient’s medical information and family contact information. It can easily be shown to law enforcement.
For more information on these resources and how to access them, please contact Doug Schulte. He is available at the following email address to answer your questions, and he asked that you specify that the message is for him: hdsainfo@hdsa.org.
Further Information:
The recording of this presentation: http://hdsa.org/about-hdsa/annual-convention/2016-convention/
The presentation slides: http://hdsa.org/wp-content/uploads/2016/06/HDSA_National-Convention-2016-Presentation-law-enforcement-1.pdf
HOPES Mobile Resource for Law Enforcement Education:
http://web.stanford.edu/group/hopes/cgi-bin/hopes_test/inform-law-enforcement/
Further information on PERT:
http://www.comresearch.org/pert.php
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What is genetic testing, and how does it work?
Genetic testing can reveal variations in genes that may cause illness or disease. It can be done predictively, to assess a person’s risk of developing a condition, or diagnostically, to confirm a diagnosis. Before deciding to undergo pre-symptomatic genetic testing for Huntington’s disease, a person usually consults with a genetic counselor. The procedure is entirely optional, and the decision to undergo genetic testing can be emotionally difficult. Therefore, it’s important to understand how genetic testing works, its risks and benefits, and consequences of test results. Informed consent is necessary; more information on this process can be found here.
In general, genetic tests are performed on a sample of tissue or fluid. This can be a cheek swab, blood, urine, hair or amniotic fluid sample. Then, the sample is sent to a laboratory, where technicians analyze it and search for a change in protein level or in DNA.
For Huntington’s disease, the genetic test is performed on a blood sample. Once it is sent to the laboratory, technicians perform a DNA test to look at the huntingtin gene, and specifically, to check for the expanded CAG repeat characteristic of HD. The goal of the test is to measure the number of repeats in the huntingtin gene. More information on DNA mutations and the CAG repeat expansion in Huntington’s disease can be found here.
You can also watch a HOPES video on genetic testing here.
How does the genetic test for Huntington Disease work?
Laboratory technicians perform a set of steps to inspect the DNA provided in the blood sample. Let’s take a closer look at each of these steps.
Step 1- The Polymerase Chain Reaction: Making many DNA copies for analysis.
The polymerase chain reaction, or PCR, is used to isolate DNA and make many copies of it. It is needed in order to make lots of copies of the huntingtin gene, allowing scientists to examine it more closely. PCR produces millions of DNA copies in a short amount of time, and includes a few steps as follows.
First, the DNA sample is heated to nearly 100o C. DNA is normally double-stranded in a helix formation, but the heat causes the strands of DNA to separate into single strands. This process is called denaturation.
Then, the sample is cooled a little. Now, primers can bind to each DNA strand. These are small molecules serving as the starting material for a reaction called polymerization. The goal of this reaction is to create more DNA. An enzyme called DNA polymerase makes new DNA strands by adding nucleotides, the structural unit of DNA, to the primer on each strand. It’s like adding building blocks to a pre-existing block tower. As more nucleotides are added, the strand is extended, and eventually, a new copy of the gene is made.
Step 2- Gel Electrophoresis: Separating fragments of DNA based on size.
After creating millions of copies of the huntingtin gene using PCR, we are now ready to separate DNA fragments, in order to inspect them more closely. This can be done using a technique called gel electrophoresis. The principle is simple: DNA fragments are separated based on their size because smaller fragments are able to travel through the gel faster than larger ones. Let’s take a closer look at how exactly gel electrophoresis is done.
First, restriction enzymes attach themselves to DNA and cut it into small fragments. Then, the DNA pieces are placed in small wells in a gel floating horizontally in a buffer solution. This solution is located between two electrodes, one positive and the other negative. Once an electric current is passed through the gel, the fragments of DNA begin to move. DNA is negatively charged, so it is attracted to the positive electrode. The smaller fragments move faster than the larger ones, so they move across a greater distance towards the positive electrode.
Step 3- Inspection of DNA Fragments: How many CAG repeats?
Now that the fragments of DNA have been separated, the technicians are ready to inspect each DNA fragment. They do this to evaluate the number of CAG repeats in the huntingtin gene.
Individuals who do not have HD usually have 28 or fewer repeats. Individuals with HD usually have 40 or more repeats.
Information on test results and what they mean is available here.
For further reading
How is genetic testing done?
Huntington’s Disease and Genetic Testing.
Learning about Huntington’s Disease.
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Hannah Boutros
January 21st, 2016
This is a short story about Tommy and his family. Tommy is an 8th grader who loves learning about the brain. After his uncle is diagnosed with HD, Tommy decides to learn more about the neuroscience behind HD so that he can explain it to others.
Today is a Monday. It is Tommy’s first day back at school after Thanksgiving. He is sitting at his wooden desk slightly hunched over, cradling his head with his hands, fully alert. His eyes are fixed on his science teacher, Ms. Robinson, who is standing at the front of the classroom, flipping through her notes.
Tommy gazes at her expectantly. He has really been looking forward to today. Ms. Robinson had announced the day before Thanksgiving that when they return from the holiday, they would start a new chapter in biology—learning about the human brain.
Tommy has been waiting for this day since the very start of 8th grade. He has always found the brain to be fascinating, mysterious, and extremely powerful. Brains allow us to do anything we want. Thanks to your brain, you can sing, dance, laugh, cry, listen, write, study, run, jump, or play a sport. How is it possible that such complex thoughts and feelings come from a single place inside someone’s head?
For Christmas last year, when he was in the 7th grade, Tommy’s mother gave him a science textbook all about the brain. Tommy knew exactly what the gift would be when he picked it up, and he couldn’t help but smile widely. It was heavy, and he could feel the edge of the book’s cover. He unwrapped it and felt its untouched spine. Tommy was eager to run upstairs and start looking at it, but also wanted to preserve its pristine condition. On the front cover, he saw that it was a book for 11th graders. He felt a warm pride deep in his chest, grasped the book tightly and grinned at his mother.
Today, that book sits under Tommy’s bed at home. He brought it to school once, but it was pretty heavy to carry around. His friend Eric was curious to see the vivid illustrations in the book, and the two of them pored over it intently during recess. When Eric lost interest, Tommy tried to show his other friends, but they didn’t want to spend their playtime looking at a textbook. Tommy decided to bring it back home. He was a little upset, but his mother said that eventually his friends would be more receptive to hearing about how awesome brains are.
Tommy’s friend Eric always sits next to him in class, and this Monday morning is no different. He nudges a sleepy Eric under their shared desk, because the lesson is about to start. Tommy knows when Ms. Robinson is about to start teaching, because she always takes one last sip of coffee out of her dark red mug, and scribbles a little bit on the whiteboard to make sure her marker is working. He can tell that she is drinking coffee, because he can always smell its strong aroma from his seat at the front of the classroom. Tommy notices that she brought a clay model of the brain. He is resolved to pay attention to everything she says today, and to take notes furiously.
Ms. Robinson looks up at her class and launches into her lesson:
“Good afternoon, everyone! Today we will be discussing the human brain. As you all know, the brain is a complex organ that helps you think, move, and feel. In adult humans, it weighs about three pounds and looks like a large, greyish-pink walnut. Just like a walnut, it is divided into two hemispheres, split right down the middle. I brought a model today to help illustrate this. Do you see how the brain is split into two halves? The left half controls the right side of the body and human speech. The right half controls the left side of the body and how we perceive space. For example, it is responsible for the perception of how distant or close two objects are to each other.
Some scientists say that the specific functions of these two hemispheres are what make us uniquely human. They help us process at a higher level, which distinguishes us from other animals. This high-level part of the brain is the most recently evolved, and is known as the cerebral cortex. In fact, each hemisphere is divided into four lobes, which you can think of as four areas of the brain: the temporal, parietal, occipital, and frontal lobes. Most animals do not have a cortex, but we do. It helps us to be creative, feel emotions, and accomplish complex tasks.
Below this walnut-like structure, we find the more primitive part of the brain, located at the base of the head near the neck. This part of our brain is very similar to that of other mammals. It is responsible for our balance and for bodily functions that we don’t consciously think about, like breathing, regulating heart rate, and sleeping. All mammals need to accomplish these functions in order to survive!”
She pauses to take a sip of her coffee and clear her throat. Tommy takes a moment to catch up on the notes he is taking. Ms. Robinson asks the class: “Are there any questions so far?” A student in the back raises her hand. “I have two questions. Which side is the front of the brain, and which is the back? And how is the brain connected to the rest of the body?”
“Both great questions! The front of the brain is where the frontal lobes are. They are right behind your eyes. The base of the brain is closer to the back, and that is where the lower brain connects to the spinal cord. This is actually related to how the brain is connected to the rest of the body, which we will be discussing next!” Ms. Robinson beams at her class.
She continues: “The brain is part of the central nervous system. As such, it is made of nerve cells, which we also call neurons. These cells carry information, called an impulse, from your body to your brain, and from your brain to your body. So for example, if you touch something hot with your finger, a sensory receptor for heat on your finger will send an impulse to your spinal cord, which is in the central nervous system. Your spinal cord processes this information, and to avoid harming your skin, it sends an impulse back to your finger to say: “get away from the heat!” All this happens in less than a second, and you quickly remove your finger from the heat source. Your nerves connect the brain to different systems in your body, and also help muscles move in response to stimuli. So they actually help you do almost everything that you do in everyday life.”
Tommy pipes up: “Ms. Robinson, what is your favorite part of the brain?” She smiles at him, adjusts her horn-rimmed glasses, and says: “I really like the amygdala. It’s a very small structure above the primitive part of the brain, but below the cortex. It’s my favorite part of the brain because despite its small size, it is quite powerful. The amygdala is part of the limbic system, which is responsible for emotions, mood, and instinct. It also plays a role in attention and memory.”
At the end of the lesson, the bell rings- school is over for the day. Tommy grabs his backpack and follows Eric out of the room, shuffling his feet. His black and white Converse match Eric’s shoes. People often say that the two boys could be twins. They are the same height, and both sport a head of dark brown curls.
As they are walking through the yard towards the gate, Eric glances up at the line forming in front of the yellow school bus, and snorts. “How is it that the 3rd graders are always out of class before we are?” Tommy smiles, and looks for his younger sister Lily in the line. More specifically, he scans for a pink Dora the Explorer backpack, and quickly locates his sister. She is chatting excitedly with Eric’s little sister Madison. Tommy overhears her exclaim: “And we have leftover pumpkin pie!”
The boys join their sisters in line, and they clamor onto the bus. Eric and Tommy sit at the far back, and Madison and Lily sit right in front of them, as they have been doing all year. Eric unzips his backpack, rummages through it, and digs out a half-eaten sandwich. With his mouth full of cheddar cheese on rye, he asks Tommy: “So how was your holiday?
Tommy replies: “I had a lot of fun. My mom spent all day Wednesday and Thursday cooking. She made my favorite cheesy broccoli dish that we always have on Thanksgiving. The house smelled incredible! And my uncle, aunt, cousins and grandparents drove here all the way from Chicago.
“That’s awesome. Sounds pretty similar to my Thanksgiving!”
Eric trails off just as the bus slowed down in front of Tommy’s house. All four kids eagerly look out the window at the garden, because Tommy’s father, Joe, is usually watering the yard at this time of day. He is not there today, but typically waves at the children and aims the water hose at the bus as if he is trying to spray the kids when they hop off. Tommy wonders why his dad is not there today.
Both boys jump up out of their seats, and nudge their sisters to get up as well. The four kids hop out of the bus, and part ways. Eric and Madison live right across the street from Tommy and Lily, so they do not have far to go.
Tommy notices that his backpack is heavier than usual today, and sets it down in the driveway. He is still thinking about Thanksgiving. He really did enjoy the holiday, but he did notice that his Uncle Jacob, who is his father’s older brother, was not acting like himself. On Thanksgiving, Uncle Jacob bumped into the dining table a couple of times. He also mumbled a lot and seemed to hesitate before speaking. Tommy noticed that Uncle Jacob was not smiling as often. After the family meal, Tommy overheard his parents whispering in the kitchen that they were worried about him. They convinced Uncle Jacob to stay in town over the weekend to have a check-up with the doctor on Monday morning.
Tommy looks up at his sister. Lily runs up to the house just as their father, Joe, and Uncle Jacob pulled into the driveway. The two men sit in the car for longer than usual, but the kids do not take notice. Tommy grabs his backpack and follows his sister into the house. “Mom, we’re home!” Lily shouts. Their mom is on the phone, facing the floor-to-ceiling glass window in their living room. Lily runs to her, and hugs her from behind. Their mom hangs up the phone, turns around, and leans down to embrace her daughter. “Hi, sweetie. How was school today?”
***
Their mom made a light lunch for the kids. They gobble down some hot tomato soup with grilled cheese, and head upstairs to do some homework. Tommy had been excited to tell his mom about everything he had learned at school about the brain, but she seems distracted. As Tommy takes his empty plate to the sink, he notices that his mother is looking at the driveway with worried eyes. He gives her a hug. “Mom, is everything okay?” She looks down at her son and says: “I hope so, honey. I’m worried about Uncle Jacob’s health. Why don’t you head upstairs to do your homework and I’ll come upstairs later to chat?” Tommy nods and squeezes his mother extra tight.
He heads upstairs, sits at his desk and unzips his backpack to pull out his math notebook. Just as Tommy is putting pen to paper, his mother knocks at his bedroom door and asks to come in. Lily peeks in from behind her mother’s skirt. The rest of the house is eerily quiet. Tommy asks: “Where are Dad and Uncle Jacob?” His mother replies, “They went for a walk.” She enters her son’s room and sits on the bed. Lily plops down next to her and says innocently: “Mommy, what did you want to talk to us about?”
Their mom sighs. Tommy notices that her eyes are red and puffy. “Uncle Jacob is unwell. He has been diagnosed with Huntington’s Disease.”
Tommy’s stomach feels funny, and he stands up with shaky knees. He manages to walk over from his desk and sit next to his mother on the bed. She wraps her arms around her children and wipes away a tear. Lily looks both scared and sad. “Mommy, what does that mean?” Their mom continues: “We are still learning what this means. We know that it affects his brain, so Uncle Jacob will experience changes in how he thinks, moves, and feels. The doctors say that his condition will deteriorate over time, so it’s important to be grateful for the time we have together. It’s very important for us is to offer Uncle Jacob as much love and support as we can. When he and your father get home, give them both a big hug, okay?”
***
Soon after that, Joe and Uncle Jacob arrive back at the house. Tommy has never seen his father cry before, but he notices that his dad’s nose is redder than usual. Lily and Tommy had been sitting on the stairs, waiting patiently for them to get home. Tommy stands up, and walks over to Uncle Jacob. He extends a hand to his uncle, and helps him walk over the doorway. Uncle Jacob, whose hair is beginning to gray, smiles down at Tommy with crinkling eyes. “Thank you, Tommy.” Tommy buries his face in his uncle’s shirt, and Uncle Jacob holds him close. Lily, in the meantime, is hugging her father.
***
The following morning, the children sleepily munch on cereal for breakfast while their mother prepares their packed lunches to take to school. Knowing that orange juice is Tommy’s favorite part of the morning, Tommy’s mom decides to squeeze fresh orange juice for the kids to drink with breakfast. Uncle Jacob walks into the kitchen just as Tommy is gulping down the last of his juice. Lily smiles shyly at him. He stands at the doorway, and doesn’t make eye contact with anyone. Tommy’s mom glances at him with worried eyes. “Good morning, Jacob. Can I get you anything to drink? How are you feeling?” Uncle Jacob glances over at her, and manages a small smile. “I’m doing fine, thank you Sue for your hospitality. I think I’d like to hang out with the kids before they leave for school.”
Tommy is glad to see his favorite uncle join him at the table. He has never seen Uncle Jacob look sad before, and doesn’t really know how to act. Regardless, they chat about the upcoming day at Tommy and Lily’s school. Tommy quickly realizes that there’s no reason not to act just like himself! A few minutes later, Sue gently reminds the children that they need to make the bus, and everyone stands up to head outside to the curb. Uncle Jacob walks with the kids out the front door to see them off. Tommy hoists his backpack onto his shoulder and walks alongside his uncle. He notices that Uncle Jacob is not walking normally anymore. He is dragging his feet slightly, and also walking lopsided.
Eric and Madison are waiting on the sidewalk, watching the trio approach. Once Lily, Tommy and their uncle arrive at the curb, Madison looks pointedly at Uncle Jacob and asks: “You’re walking funny today.” Uncle Jacob cracks a smile but his eyes look sad. His voice trembles but he says: “I know. I have been feeling sick recently.” Tommy feels confused and sad. Madison shouldn’t have treated Uncle Jacob that way, even if she doesn’t know any better. She doesn’t even know Uncle Jacob that well.
Tommy hugs his uncle extra tight before boarding the school bus. He sits at the back next to Eric and leans his head against the glass window. People don’t understand why Uncle Jacob has been moving and behaving strangely. It probably has to do with changes to his brain, just like Tommy’s mother said. Tommy remembers his neuroscience lesson from yesterday, and decides he wants to learn more. He is resolved to find someone to explain it to him.
He would have asked Ms. Robinson if she knew anything about Huntington’s Disease, but his schedule does not include science class on Tuesdays. After school, Tommy runs upstairs to his bedroom and pulls the neuroscience textbook from last Christmas out from under his bed. Laying on his stomach on the bedroom floor, Tommy looks for a glossary at the back of the book. Under the letter “H”, he finds Huntington’s disease, and reads: “Huntington’s Disease is an inherited condition characterized by the breakdown of nerve cells over time. Progressive movement, cognition, and psychiatric symptoms tend to appear.”
***
The next day, there is no school due to a teachers’ in-service day. Tommy accompanies his father and Uncle Jacob to a doctor’s visit, and is feeling ready to ask some questions about Huntington’s Disease. Tommy sits in the waiting room during Uncle Jacob’s check-up, and peeks his head in at the very end to ask Dr. Peterson if he has time to answer a few questions. Dr. Peterson emphatically nods his head to say yes, and Tommy steps inside the room, walks over to the bed where Uncle Jacob is reclining but wide awake. Tommy leans against the side of the bed, resting his hand on his uncle’s shoulder. Joe is sitting in a chair near the doctor’s desk.
“Dr. Peterson, I really want to understand what happens in the brain when someone has Huntington’s Disease.”
“That’s great, Tommy. Why is that?”
“I find the brain really interesting, but more importantly, I want to be able to explain it to others who ask or are curious. People don’t seem to understand what Uncle Jacob is experiencing and I don’t want his feelings to be hurt.”
“Well, young man, I really appreciate your sensitivity, and I’m sure your uncle does too. I’d be happy to give you an overview of the disease. Huntington’s Disease is also known as HD. It is quite rare—it affects about one in every 10,000 people in the United States, and usually appears between 30 and 50 years of age. Many of the symptoms of HD can be explained by changes to the brain. There are movement, psychiatric and cognitive symptoms. Movement symptoms of HD can include muscle spasms, tics, rigidity, and difficulty speaking. There can also be uncontrollable movements like twisting and writhing. Symptoms affecting the brain include difficulty learning new things, and impairment of spatial perception. For example, Uncle Jacob mentioned to me that he bumped into the table during Thanksgiving, and that might have happened because he thought it was further than it actually was in real life.
There can also be difficulty planning and multitasking, since information processing in the brain is slowed and altered. Uncle Jacob sometimes has difficulty communicating with others, because is has gotten hard for him to organize words in his brain. Lastly, depression is a common psychiatric symptom for HD. So it’s important to show Uncle Jacob lots of love and support.”
“Thanks Dr. Peterson, that’s really helpful. So what is happening in Uncle Jacob’s brain?”
“Uncle Jacob’s ability to think, feel, and move is changing. This is happening because nerve cells, also known as neurons, in his brain are deteriorating in certain areas, like the basal ganglia and the cerebral cortex, which I’ll explain in a minute. HD is a progressive, neurodegenerative disorder: this means that over time, involuntary muscle movements develop, and the ability to think and remember deteriorates.
The disease affects the basal ganglia, which is part of a circuit linked to the thalamus. This part of the brain is most affected by the disease, and many of the symptoms result from damage to this circuit. The basal ganglia sits at the base of the brain, and is involved in the coordination of movement by muscles. In fact, the striatum in the basal ganglia is the first to lose nerve cells. As this happens, pathways between the basal ganglia and the motor cortex are damaged. This is why coordination of movement is affected in the disease. The motor cortex, usually responsible for the planning and execution of movements, can no longer do its job properly because it is not stimulated enough. This likely leads to the slow speed of motor movement of HD patients. Tommy, are you familiar with the word “cortex”?
“Yes, I am. We just learned about it in class yesterday. I know that the cortex is the high-level part of the brain in humans.”
“That’s right. If you were to look at a human brain, you would see gray on the outside and white on the inside. That’s because the cell bodies of our neurons are on the outside of our brains, and look gray: this part of the brain is the cortex. The extensions off those cell bodies project towards the center of the brain, and are white due to a fatty substance called myelin. Anyway, initial loss of cells in the basal ganglia leads to cell loss from other regions that are not getting feedback anymore. All of these things happen in the brain, and lead to behavioral symptoms that are visible to us.
“OK. You mentioned that there are emotional symptoms. Does something in the brain lead to that?”
“Indeed. Huntington’s Disease progressively damages the caudate nucleus, which is a relay station between the limbic system and the frontal lobes. The limbic system controls emotions, while the frontal lobes are really important in personality, in emotion regulation, and in responding to emotions. So in HD, there is a disconnect between emotion processing and response to emotions. This produces apathy or lack of interest, a common symptom of HD.
“Dr. Peterson, do we have a cure for HD yet?”
“Not yet, but researchers are hard at work trying to find one. There is a buildup of plaques in the brain that we still don’t understand, and lots of research is being done there. Scientists are currently trying to determine whether that is the cause of toxicity, because if so, we will know what to target for treatment. Meanwhile, there are therapies available to mitigate symptoms.”
“Thank you so much for explaining this to me.”
“Of course, I am happy to help. Let me know if you have more questions.”
Tommy shakes Dr. Peterson’s hand, and Joe stands up to leave. Along with Uncle Jacob, they make their way out of the office.
***
The next day is Thursday. It’s been exactly a week since Thanksgiving, but to Tommy, it feels like much longer. So much has happened, and his life feels like it has changed very much. At breakfast that morning, Tommy sits next to Uncle Jacob so that he can crack jokes and try to make his uncle laugh.
On the bus, Eric is playing with a Rubik’s cube. He and Tommy talk about the toy for a while, and marvel at how difficult it actually is to solve them. Madison and Lily, who are sitting in front of their brothers, notice how much fun the boys are having. They turn around to face Eric and Tommy, and watch the boys play with the cube. The four of them chat about the toy.
A while later, shortly before arriving at school, Tommy remarks to Madison: “Hey, do you remember the other day when my uncle was walking funny?”
She looks at him with large brown eyes. “Yeah. He said he was sick. I hope he’ll be ok!”
Tommy replies: “Thanks, Madison. He has Huntington’s Disease, which does not have a cure. Over time, his ability to think, feel and move will be affected more and more. I am hoping that we can all treat him with respect even if he moves or acts differently than we do. Over the week I spent some time learning about the changes that happen in the brain due to Huntington’s Disease, so if you’re curious about that I can try to explain it to you!”
Madison nods energetically. “I understand. Thanks for explaining that to me.”
Tommy smiles. “Of course!”
He sits back in the cushy bus seat, feeling much better. Tommy is confident that with the right words, he can help people understand that HD patients are just people too. Madison is a little young to hear about the changes HD causes in the brain, but he knows the knowledge will come in handy in the future. Tommy grips his backpack and excitedly sways his legs, eager to get off the bus. Maybe Ms. Robinson will have something to say about this too.
Up next: Tommy learns about the genetics of Huntington’s Disease. His cousin, Uncle Jacob’s son, is debating whether or not to get tested next year when he turns 18. Stay tuned for another short story, where Tommy learns about genetic testing and how HD is transmitted in families.
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