Agora: Red Deer Polytechnic Undergraduate Journal
Volume 16:1 2025 Agora Conference Proceedings

The Psychology of a Genetic Curse:
Nancy Wexler and the Impact of
Huntington’s Disease
Brooke Schwartz
There are countless amounts of people facing hardships
in everyday life, and it can lead to the belief that life is simply
unfair. However, for many, this thought is retracted and an
overwhelming sense of gratitude is achieved when they discover
the life that Nancy Wexler, and several others, are forced to
endure. Nancy Wexler, and a multitude of other individuals,
have a neurodegenerative disorder called, “Huntington’s
disease” (WETA National Productions, 2020). The disease is
hereditary, as the gene responsible is autosomally dominant
(Ciriegio et al., 2020). This means that individuals with affected
parents, have a 50/50 chance of inheriting Huntington’s disease
as well, which became the reality of a geneticist named, Nancy
Wexler. Unfortunately, many of Nancy’s family members,
including her mother, were affected by the disease and passed
away because of it (Grady, 2020). Since no known treatment or
cure to offset the symptoms existed, she dedicated her life to
discovering one, for her family members and ironically one day,
herself. Although much of her findings contributed profoundly
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to Huntington’s disease research, Nancy was unable to establish
an effective treatment, and there is currently no known method
of entirely diminishing the effects of the disease (National
Institute of Neurological Disorders and Stroke, 2024). Today,
she suffers with the symptoms of the disease, awaiting a cure to
save her from her poorly dealt hand in life (WETA National
Productions, 2020). Research for Huntington’s disease is crucial,
and many areas can be explored in an attempt to understand the
impact of this neurodegenerative disorder on the psychological
domains of emotion, sensation, cognition and behaviour. An
understanding of the physiological effects of living with
Huntington’s

disease,

and

the

adverse

psychological

repercussions, as well as research on different kinds of
treatment, will be investigated in an attempt to analyze this
disorder in which thousands of people endure in today’s society.
Nancy Wexler is a well established geneticist who
devoted her life to researching Huntington’s disease, which
entailed indagating the gene associated and experimenting with
treatments to the affected gene (Grady, 2020). She spent
approximately 40 years researching the gene, which included
visiting remote villages of Venezuela where a large number of
affected individuals resided. With desires to use the genetic
information of these individuals, she raised millions of dollars,
created a clinic, and eventually discovered the gene associated

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with Huntington’s disease in 1993, HTT. This led to being able
to begin creating a drug which could have an effect on the gene
that may possibly cure the disease, as well as creating a test so
individuals could confirm whether or not they were living with
the gene. Growing up, she was exposed to multiple different
family members living with Huntington’s disease, which
inevitably put her at risk for having inherited it. Her mother,
uncles, and grandfather all died due to the disease, and her
brothers were diagnosed. She chose her career path in an attempt
to one day find the cure and destigmatize the degenerative
disease, to save her brothers. For much of her life, she was in
denial that she would ever fall victim to the oppressive disease
as well. Throughout her career, she chose to keep her probable
diagnosis quiet, and never discussed the possibility with her
colleagues. It wasn’t until she was 74 that, she acknowledged
she too had inherited Huntington’s disease, but she was then too
old to qualify for a clinical trial for the drug she had created.
Being surrounded by people close to her having Huntington’s
disease, as well as the possibility of having it herself, influenced
Nancy tremendously. She dedicated the entirety of her
professional career to researching Huntington’s disease, and
attempted to promote further research, educating others about
how it works and affects people.

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Huntington’s disease is present in individuals who have
a mutation on their HTT gene, a protein called “huntingtin”,
which resides on chromosome 4 (National Institute of
Neurological Disorders and Stroke, 2024). Specifically, these
individuals have an excess of the cytosine, adenine, and guanine
trinucleotide repeat on this gene. Normal DNA repeats of these
nucleotides exist around 27 times, individuals who likely won’t
develop the disease, but could pass on the gene have around 27
– 35 repeats, and affected individuals typically are found to have
36 or more repeats. When an individual experiences this genetic
abnormality, areas of the brain responsible for motor activity
control is compromised. Nerve cells in these areas break down
and die, reflecting the neurodegenerative nature of Huntington’s
disease. The neurotypical role of these cells is to coordinate and
maintain voluntary movements, as well as other similar areas.
Since these brain cells undergo reduction over time, it makes
Huntington’s disease characterized by a gradual decline in motor
ability, and a slow increase in corresponding symptomatology.
The disease is not sex-linked, so it is not limited to one gender,
and no gender has a greater risk of development than the other.
However, certain studies have found links to individuals of
European descent being more greatly affected than those of other
races (Ciriegio, 2020). For many, Huntington’s disease is
inevitable and lifestyle choices cannot change the outcome of

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the mutated gene living within them. Inheriting the disease is
nothing more than an unfortunate hand in life, and it reflects why
Nancy Wexler was so passionate about creating a cure and
reducing stigma surrounding Huntington’s disease. Especially,
considering the corresponding symptoms that a diagnosed
individual has to live with.
The neurodegenerative essence of Huntington’s disease
is represented by the corresponding symptoms a diagnosed
individual experiences or is likely to eventually experience after
onset. In the beginning, symptoms are minor and could
potentially even go unnoticed, which was the case for Nancy
Wexler (Grady, 2020). It was apparent to her peers and
colleagues that she was living with the mutated huntingtin
protein long before she realized the reality of the situation
herself. Until she reflected on videos and recordings of herself,
she was clueless to the related symptoms her body was
displaying. After the review of video clips, Nancy saw that she
was moving in involuntary ways, and each time she watched a
new video, the movements worsened. Her first symptoms
included having an unsteady gait, slurred speech, uncontrollable
movements in her head and limbs, a short temper, and she
required a walker to get around. Her associates began to see
aspects of Nancy changing, such as spilling drinks more, strange
body movements, and dishevelled handwriting. Prior to onset,

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Nancy never experienced these things, making it clear to others
what was going on inside her brain. Progressively, her health
declined as the motor neurons continually broke down, creating
a lack of motor ability among other symptoms. Presently, she
struggles to talk and muscle spasms are prevalent, along with the
other symptoms that have worsened as well (WETA National
Productions, 2020).
Not specific to Nancy, other general and related
symptoms of Huntington’s disease include chorea, which is a
term describing the involuntary movements an individual will
typically undergo, difficulty walking, and muscle tremors
(National Institute of Neurological Disorders and Stroke, 2024).
Furthermore, they may experience issues with swallowing and
speaking, seizures, and a loss of energy. On a more
psychological level, patients often fall into a depressive state, or
are anxiety ridden, and they could possibly deal with
experiences of hallucinations, delusions, and other confusions.
Areas of the brain responsible for organizational skills and
planning have also been impaired by the disease. Another
finding details that people experiencing the side effects of
Huntington’s disease will endure more extreme and noticeable
symptoms when they are nervous or stressed. The onset of
symptoms typically occurs around middle adulthood, ages 30 –
50 years old (Tillerås et al., 2020). The symptoms of

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Huntington’s disease are debilitating and take a great toll on an
affected person's quality of life, let alone lifespan. Eventually,
they lose the ability to work, drive or generally care for
themselves independently (National Institute of Neurological
Disorders and Stroke, 2024). Nancy Wexler, among others, are
forced to deal with the aversive effects of Huntington’s disease,
since there is no known cure to rid them of their demons, evoked
by the abnormal gene they inherited.
Living with the condition of Huntington’s disease is
evidently burdensome, so a desire to find out whether or not you
may be living with the mutation, may be a more complex
decision than expected. Tillerås et al. (2020) investigated the
psychological needs of individuals at risk of being diagnosed
with Huntington’s disease as well as those both positively and
negatively diagnosed. The researchers hypothesized that there
would be a range of reactions and emotions towards diagnosis,
and they sought to draw conclusions about understanding the
depth of mental health effects regarding Huntington’s disease
(Tillerås et al., 2020). To do so, 33 participants consented to
genetic testing to see if they carried the repeat in the HTT gene.
The participants underwent semi-structured interviews before
and after genetic testing was performed, allowing researchers to
thoroughly evaluate the emotional states and feelings of the
individuals.

Reactions

and

emotional

182

contexts

were

documented, and then understood through a thematic analysis.
The study found that many individuals made decisions with the
possibility of being diagnosed in mind, some irreversible, prior
to getting genetic testing and truly knowing if they one day
would develop the effects of Huntington’s disease. There were
both negative and positive reactions to a person finding out they
had the mutated gene, as well as finding out they did not. Since
many people anticipated having Huntington’s disease, for
reasons such as their parents having it or maybe even early
symptoms but did not end up being diagnosed, a feeling of regret
for certain choices consumed them. Although it could be
assumed that primarily feelings of optimism would be elicited
from the knowledge of healthy genes, having made irreversible
decisions under the assumption the test would be positive may
bring upon unpleasant feelings. Similarly, survivors' guilt was
found in individuals who did not have it, but realized their
sibling could or did have it. This type of research is important
for mental health practitioners who are dealing with an
individual in any of these situations, as well as for general
awareness regarding the mental health impacts of Huntington’s
disease.
As mentioned, the assumption that a person carries the
mutated HTT gene prevails in individuals who are at risk, which
inevitably creates an anxiety ridden mindset towards the future.

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Offspring of diagnosed individuals are at a relatively high risk
for also one day facing the hardships of the disease. Ciriegio et
al. (2020) sought to gain a better understanding of the stress
faced by the offspring of parents with Huntington’s disease.
Prior to this research study, it was found that stress can impair
both executive function skills and secondary control coping
skills, such as positive thinking and dealing with adversity at
general ease (Ciriegio et al., 2020). The researchers
hypothesized different correlations between the factors of stress
and levels of anxiety and depression. All of which were pointing
towards the general expectation that stress would significantly
impact offspring of diagnosed individuals, comorbidly with
anxiety and depression. Ciriegio et al. (2020) used a study
population of adolescent and young adult offspring, whose
parents' ages ranged between 32 – 58, generally when onset
would have begun. To test their hypothesis, the researchers had
the participants complete a questionnaire on a secure online
database, called REDCAP (Ciriegio et al., 2020). This revealed
demographics and coping strategies, then two more assessments
were completed, one in which was to analyze stressors and
strategies, RSQ-HD, and one for the symptoms of anxiety and
depression, YSR and ASR. Finally, the “List Sorting Working
Memory Task” was used to assess working memory. The data
was collected through the self-report tests, and the findings

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proved the initial hypotheses. Understanding the mental health
risks that pertain to individuals at risk for developing the disease
is arguably just as important as the mental health of a diagnosed
individual. Nancy Wexler experienced similar stress towards the
anticipation of developing the disease, which is reflected in her
devotedness to find a cure. Although unprovable without
knowing Nancy personally, if she was not worried at all about
how the disease may possibly affect her one day, why was she
so hesitant to take predictive testing?
Diagnosed individuals face stress regarding their health,
perhaps in different ways than a person in anticipation would.
Once diagnosis has been completed, stressors would turn to a
reduction in lifespan and the future inability to live their
everyday lives how they are used to living them. Ciriegio et al.
(2022) conducted a study that intended to draw conclusions
about the coping mechanisms of stress in diagnosed individuals,
along with the associated symptoms of anxiety and depression.
It was hypothesized again that there would be associations
between control and attention, working memory, secondary
coping skills, and anxiety and depression, all pointing towards
stress and similar symptoms of anxiety and depression
prevailing in individuals with Huntington’s disease. The
participants included adults aged 31 – 69 who were diagnosed
with the disorder (Ciriegio et al., 2022). To understand the stress

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associated with these participants, assessments were done using
an anxiety self-report scale, GAD-7, and a depression self-report
scale, PHQ-9. Results of these tests were analyzed and
significant effects were found between inhibitory control and
attention skills and symptomatology of anxiety and depression.
Along with, between secondary control coping skills and
anxious and depressive symptoms. The findings of these tests
signify the impact that having Huntington’s disease has on an
individual relating to stress symptoms, such as control and
attention skills, secondary control coping, as well as the effect it
has on anxiety and depression. The importance of these findings
again provides informative insight into what diagnosed
individuals deal with, like Nancy Wexler.
Anxious and depressive feelings are common factors
found to be seen in individuals either diagnosed with
Huntington’s disease, or even having a probable diagnosis, such
as being an offspring (Ciriegio et al., 2020). So, it wouldn’t be
shocking to also understand that suicide in Huntington’s disease
is not uncommon. Lipe et al. (1993) explored the risk factors for
suicide in diagnosed individuals, in a retrospective research
style. Prior evidence suggests an increased frequency of suicide
in Huntington’s disease patients, with it being most prevalent in
the earlier stages of the condition. The researchers hypothesized
that consistent themes would be found between the diagnosed

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individuals who had died by suicide, along with individuals at
risk and individuals close to those affected (Lipe et al., 1993).
Participants included eight males and one female diagnosed with
Huntington’s disease, one female with a probable diagnosis, and
one unaffected female spouse, with ages ranging between 24 –
65. The study population was compared against a control
population of similar diagnosed people who did not commit
suicide. Through the revision of medical, genetic counselling,
and social work records, the researchers made comparisons
between the obtained data and the matched data of the living
individuals. Several findings were discovered, which included
common risk factors found among the deceased individuals. The
highest found risk was having little family support and no
contact with children. Other predictors were being male, having
no offspring, other suicides in the family, living alone, being
unmarried, depressed, and having little contact with other
people. Figuring out the prevailing factors that contribute to an
individual with Huntington’s disease dying by suicide are
substantial for many reasons. The value of a diagnosed
individual's life does not decrease because of the condition
taking over their mind and body. Family and friends close to
them likely don’t see them differently and are devastated by such
news, not to mention the life lost that still had so much potential,
regardless of ability. Although these individuals may lose hope

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and see no reason to live anymore, they must have a support
system that understands their feelings and can support their
mental health journey, which is frankly exactly why this type of
research is so vital.
As discussed, research regarding Huntington’s disease is
crucial for a variety of reasons, made even more apparent when
reviewing the research surrounding the aversive mental health
effects of the disease. Nancy Wexler being so closely associated
with individuals suffering from a diagnosis understood this all
too well, and was a part of imperative research exploring the
causes and genetic makeup of Huntington’s disease. Lee et al.
(2020) researched the mutant gene, HTT, analyzing how the
disease progresses and ways in which this progression could be
reduced. Nancy Wexler was one of the geneticists involved in
this study, where they hypothesized that the huntingtin protein
responsible for Huntington’s disease would undergo seeding, or
proliferation, effectively progressing the disease. Once
understanding the proliferation process, the goal of the study
was to develop a way to decrease the seeding activity, through
the targeting of specific parts of the mutated gene (Lee et al.,
2020). Mice were the study population of choice, used to
understand how the mutant HTT gene worked in humans as well.
A cell line was produced to detect seeding activity, then
characteristics of the disease were able to be analyzed, serving

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as a cell-based tool. Specifically, an increased expression of the
DNAJB6 molecule and the anti-polyP antibody were used to
inhibit proliferation, leading to insights regarding mechanisms
to cure Huntington’s disease. Undoubtedly, Nancy Wexler was a
part of contributing to Huntington’s disease research, and this
study specifically had a large impact on the advancements of the
sought out cure for affected individuals.
Despite a successful medical treatment of sorts that
would ideally slow down the progression of the impact of the
mutated Huntington’s disease gene being the primary goal of
researchers, other treatments aimed at reducing symptoms are
also functional for suffering patients. Research into alternatives
serves as important, especially until a medical treatment
targeting the gene is successful in the future. For example,
cognitive behavioural therapy was proposed by Meyer et al.
(2022) to treat post-traumatic stress disorder (PTSD) and
obsessive-compulsive (OCD) in a Huntington’s disease patient.
Existing research reported significant findings of individuals
diagnosed with Huntington’s disease comorbidly dealing with
obsessive-compulsive symptoms (Meyer et al., 2022). As well,
research has been done on treating these symptoms with
pharmaceuticals, which have been primarily ineffective at
eluding the symptoms altogether. Thus, other treatment
methods, such as cognitive-behavioural therapy, hold a need to

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be studied. The researchers hypothesized that this type of
therapy would be a better approach to treating OCD-related
symptomatology, and they chose a single participant to perform
the case study on. Prior to this case study, it was predicted that a
Huntington’s disease individual would not be receptive to this
type of therapy, but this did not affect the researchers’ decision
to pursue this treatment. The Huntington’s disease diagnosed
individual chosen was a 43-year-old male experiencing both
OCD and PTSD, where pharmaceutical treatments in the past
merely relieved symptoms temporarily, but proved ineffective
long term. To study the effects of cognitive behavioural therapy,
the participant underwent exposure to his past trauma, as well as
exposure therapy for his obsessive-compulsive tendencies
toward cleanliness. He was evaluated using the Problem
Behaviours Assessment,

the

Montgomery

and Asberg

Depression Scale, Yale-Brown Obsessive-Compulsive Scale,
and DSM-5 Criteria for PTSD. Evaluations were completed both
before and after ten, one hour cognitive-behavioural guided
therapy sessions, over the course of ten weeks. PTSD and OCD
symptoms completely resided, proving this treatment method
effective in the reduction of comorbid Huntington’s disease
effects. This is substantial for individuals with Huntington’s
disease also struggling with similar outcomes. Additionally,
these results proved that Huntington’s disease affected

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individuals do hold the capacity to be treated by cognitive
behavioural therapy.
Not only has cognitive-behavioural therapy been proven
to yield as effective in reducing symptoms relating to
Huntington’s disease, but so have rehabilitation programs
catered to the needs of these individuals. Piira et al. (2013)
reviewed prior research by Zinzi et al. (2007) and aimed to
conduct a rehabilitation program that filled the gaps of this study,
showing improvement and maintenance of physical and
cognitive functioning in Huntington’s disease individuals. The
researchers hypothesized that through a one-year program
consisting of three in patient stays of three weeks, that their
improved plan would yield decreased side effects of
Huntington’s disease, more so than the prior study mentioned.
Their rehabilitation program contained more assessments
including quality of life, function in daily activities (ADL),
motor and cognitive function, and improved follow up tactics to
increase sustainability. 37 patients were enrolled in the centres
providing the program, who all had early to middle stage
Huntington’s disease. Evaluations such as the Mini Mental State
Examination,

a

cognitive

assessment

(UHDRS),

an

anxiety/depression symptoms assessment (HADS), and an
assessment of quality of life (SF-12) were used to compare
baseline levels to results after treatment (Piira et al., 2013).

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Symptoms that improved due to the program included gait,
balance, mental state, anxiety and depression, and physical
quality of life. This shows that anyone dealing with these
symptoms because of Huntington’s disease would benefit from
this type of program aimed at treating the effects of the disease.
A shortcoming in the results was that the mental component of
quality of life did not significantly improve, but with all the other
advancements the rehabilitation program is objectively
worthwhile. Nancy Wexler, and others, may be after a
pharmaceutical cure but other types of treatment may aid in
improving symptoms, at least enough to increase the standard of
living in Huntington’s disease patients to some degree.
Huntington’s disease is associated with its unfavourable
outcomes, greatly decreasing an individual's overall wellbeing
through many different areas of life. Nancy Wexler committed
herself to finding a cure, but now lives with symptoms inhibiting
her motor control abilities that negatively affect her everyday
life. As stated, Huntington’s disease has been proven to break
down areas of the brain associated with motor ability and control
at a neurological level (National Institute of Neurological
Disorders and Stroke, 2024). The result can be seen in the
various behavioural side effects discussed, such as chorea and
other motor inabilities. To go along with this, the area of the
brain deteriorating lacks proprioception sensation abilities,

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related to difficulties in motion and positioning of the body.
Furthermore, individuals are affected emotionally, often
experiencing depressive and stressful symptoms, both seen in
the diagnosed population and their offsprings or close family
members (Ciriegio et al., 2020). Cognitive abilities are also
proven to be disturbed when a diagnosed patient begins to lack
organizational abilities (National Institute of Neurological
Disorders and Stroke, 2024). Nancy Wexler is a prime example
of the effects Huntington’s disease has on a person, as well as
the participants involved in the research studies utilized in the
investigation of the genetic disorder. The survey of the literature
evidently proved that the neurological condition, Huntington’s
disease, impacts the psychological domains of emotion,
sensation, cognition, and behaviour, to varying degrees
depending on the stage of the disease.

193

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