Biophysical
& Biochemical Changes in Long-Term Disease States
Melissa
J. Dawson
Southern
New Hampshire University
PSY
300 Biopsychology
Introduction
In prior classes I have
read many articles about how a child’s brain and nervous system develop, what
are standard behavior and action milestones, how do the hormones of puberty
affect thought and emotions, the psychology of work, parenting and being a
partner, the psychological effects of PTSD in Veterans and even discussions around
how the median aging process affects perceptions and reactions. What I have
struggled to find are academic and peer-reviewed studies on ways that facing
personal mortality in combination with potential long-term medications for
chronic conditions affect a person’s overall psychological make-up, which in
term affects those around them.
For example: What are the biochemical
changes or triggers that occur in a cancer patient who has been exposed to a
year of chemotherapy and has a prognosis of six months to live once they stop
chemo versus a diabetic patient with failing kidneys who also has chosen to
stop treatment such as dialysis. What affects the patient more keenly in their
last months? The exposure to strong medications and treatments that are difficult
physically – or the support of people around them, or the lack thereof. Can we
show that specific drug therapies leave genome markers that can be linked to
specific behavior and thought misalignments which could make the transition
process more stressful or psychically more damaging than is necessary?
Many
patients diagnosed with progressive, long-term disease states are already being
tested via bloodwork as a part of the general care management protocols. My
proposed study would add peptides, hormones and proteins to the blood work done
on patients with these chronic conditions. By comparing these levels in
patients with the same diseases who are in hospice or palliative care researchers
should be able to see which factors are different from the levels expressed in
stable patients. Regular blood collections for many disease monitoring is not
uncommon so patients will be used to the process. As any participant within
hospice will only donate blood samples as they are comfortable doing so and may
stop their participation at any time.
Literature
Review – Article Summaries
1.
Andrewes, H. E., Drummond,
K. J., Rosenthal, M., Bucknill, A., & Andrewes, D. G.
(2013). Awareness of psychological and relationship problems amongst brain
tumour patients and its association with carer distress. Psycho-Oncology, 22(10),
2200–2205. Retrieved from https://search-ebscohost-com.ezproxy. snhu.edu/
login.aspx ? direct =true&db =psyh & AN =2013-35253-008&site=eds-live &
scope = site
(2013). Awareness of psychological and relationship problems amongst brain
tumour patients and its association with carer distress. Psycho-Oncology, 22(10),
2200–2205. Retrieved from https://search-ebscohost-com.ezproxy. snhu.edu/
login.aspx ? direct =true&db =psyh & AN =2013-35253-008&site=eds-live &
scope = site
Summary: They had
postulated that brain tumor patients were more likely to underestimate the
impairment to their psychological condition, including relationships, emotional
states, cognitive function and impact on their carers. This was in comparison
to other brain surgery patients with non-tumor patients. This was shown to be
accurate after their data analysis was completed.
Summary: When adolescents self-medicate with alcohol there is enhanced dopamine
neurotransmission which increases the user’s sense of wellbeing, which in turn
tends to lead to larger and larger amounts of alcohol consumption to regain, or
hold onto, the positive neural feedback they experience. And that the effect is
most likely to become detrimental when started as teenagers as opposed to
adulthood.
Summary:
While this team was focused
primarily on using neurophysiological testing methodologies to assess brain
function, damage and potential for healing or ultimate decline, there are good
possibilities to use this type of testing in other patient populations. We know
that in military personnel with Traumatic Brain Injury (TBI), there can be
changes in temperament, moods and cognitive functions. If these testing methods
are able to detect disruptions in neural pathways and specific brain areas that
are known to be linked to specific functions, the data could be calibrated to
assess and treat other critically ill patients.
Artery Disease
Patients: Associations with Thyroid Hormones, N-Terminal Pro-B-
Type Natriuretic
Peptide and High-Sensitivity C-Reactive Protein. Archives of
Clinical
Neuropsychology. 32(2). DOI:
10.1093/arclin/acx004
Summary: To determine whether biomarkers of
health such as serum levels of free triiodothyronine (fT3), total
triiodothyronine (TT3), N-terminal pro-B-type natriuretic peptide (NT-proBNP),
and high-sensitivity C-reactive protein (hsCRP) impact the cognitive
functioning of coronary artery disease (CAD) patients. The authors not that
there does not seem to be any published studies to date that have looked at
association between cognitive functioning and the hypothalamus-pituitary-thyroid
ais in patients with CAD, they also note there are a dearth of studies looking
at the axis and other long-term health conditions.
. Summary: Congestive Heart
Failure (CHF), as a result of Type 2 Diabetes, is an underlying cause of
depression and cognitive dysfunction. A specific peptide (NT-proBNP) is a
marker of CHF and patients with a rise in this peptide show a statistically
significant risk factor for cognitive dysfunction.
6. Kellehear, A. (2017). Unusual perceptions at the end of life:
limitations to the diagnosis of
hallucinations in palliative medicine. BMJ Supportive & Palliative Care, 7(3),
238–246. https://doi-org.ezproxy.snhu.edu/10.1136/bmjspcare-2015-001083
hallucinations in palliative medicine. BMJ Supportive & Palliative Care, 7(3),
238–246. https://doi-org.ezproxy.snhu.edu/10.1136/bmjspcare-2015-001083
Summary: Current state-of-the-art in
hallucination studies does not warrant broad or uncritical use of this type of
diagnosis in end-of-life care. Conclusions from interdisciplinary (as opposed
to single discipline) hallucination studies suggest that the way forward for
clinical and research work in palliative medicine may lie in a more
biographical and cultural approach to unusual perceptions at the end of life.
Researchers are looking at whether there are biochemical reasons for the
accounts of hallucinations and visions in people who are dying.
Summary: The present study revealed key themes related to how
patients come to terms with their impending death. Nurses are required to
comprehend the patients’ complicated mental patterns that are expressed in
their daily languages. Furthermore, the findings clarify the necessity for
nurses to help patients understand the acceptance of a terminal disease state
during a patient’s final days. A better understanding of the biochemical
changes occurring in terminal patients can help caregivers better address
cognitive decline in patients.
Literature Review – Summation of Changes and Relevance in the Field
Within a book published
in 1963 I found an interesting chapter outlining why the Greek philosopher
Aristotle should be considered the father of Biopsychology (Kantor). It is
apparent that Aristotle did postulate that within biological organisms,
including man, there was a link between the psyche and the biological functions
of the body:
“Metaproposition
i. Psychological Events are Phases of biological Events. Inasmuch
as psyche
is in some sense the principle of animal and plant life psychology must be
a special
part of biology. It concerns the functions or acts of organisms as over against
their
structure or organization, and their development or evolution.” (Kantor, pg 122)
However more current research has
been able to show not just that there is correlation, but is now identifying
specific neural pathways and the neural transmitters that regulate those
pathways. The field has moved past the superstitions of the Middle Ages that
labeled anyone with a mental disorder a witch or possessed. Past the Victorians
and their belief that humors in the air were the cause of disease and any
mental or personality disorder. Past a time where those with certain
psychological malfunctions were locked up in institutions and subjected to a
barrage of treatments and medications that often did more harm to the patient. And
past the belief that willpower, a better diet or an herbal supplement are all
you need to reverse any psychological condition.
Literature Review
– Technology and Ethics
As technology within the medical
sphere has evolved and become more sensitive to specific biologic functions, scientists
are able to now “see” into the brain and the affected or responsive areas when
a memory or other stimulus is introduced in the study subject. The field has
moved past a carpet-bomb approach of medications which did little but sedate a patient
to targeted hormone and neuroreceptor formulations that address only a specific
misfunctioning structure. And moving forward the area of Deep Brain Stimulation
(DBS) and externally applied electrical interventions show potential to re-wire
misfiring neural centers without damaging large portions of the cerebral cortex
as was seen in early use of shock therapy devices.
Information shared between various
medical disciplines has, and will continue, to aid researchers and practitioners
in finding the most efficacious and least disruptive methods to help the person
dealing with a psychological disorder. There have been limitations of course,
especially as they relate to what is ethical by current standards. Prior to
1920 there seems to be little focus on whether any medical experimentation or
research trial might be not just physically damaging to a participant, but
emotionally and mentally as well. And while Science does owe gratitude to those
who passed on structural and functional information about how the body works,
their methods would be completely abhorrent to us if conducted today.
Modern clinical trials now focus on
participant feedback, blood tests for antigens and neural receptors and
external scanning such as MRI or CAT technology. In some ways this may be seen
as slowing down the rate at which we are able to discover and learn, but
societal norms insist that people are not lab rats and need to be treated with
more care and dignity than they have experienced in the centuries past. Even
lab rats are treated better today than human subject were just 200 years ago.
Research
Design
Research Gap
As I mentioned in the introduction, my literature
review was focused on looking at the data available which would identify any
significant trends in current data that showed a causal relationship between
ingested medications, or other chemical substances, and the expression of
neural transmitters or hormones.
What are the
biochemical changes or triggers that occur in a cancer patient who has been
exposed to a year of chemotherapy (Chemo-brain, 2017) and has a prognosis of
six months to live once they stop chemo versus a diabetic patient with failing
kidneys who also has chosen to stop treatment such as dialysis. What affects
the patient more keenly in their last months? The exposure to strong
medications and treatments that are difficult physically – or the support of
people around them, or the lack thereof (Azabou,
2017). Can we show that specific drug therapies leave genome markers
that can be linked to specific behavior and thought misalignments which could
make the transition process more stressful or psychically more damaging than is
necessary?
Research Question
My research premise is:
Within the Hospice community
there is a period of time for each patient when they are said to be
“pre-actively dying” that refers to not a shutting down of the physical body
which occurs in “active dying”, but a period of introspection and wanting to
resolve unfinished inter-personal relationships. At the same time, their body
and brain are reacting to the bio-chemical changes that chronic medication use
or the disease itself are creating. Can we show that specific drug therapies or
disease states leave genome markers that can be linked to specific behavior and
thought misalignments which could make the transition process more difficult
physically or psychologically more stressful than is necessary?
Research Design
Proposed: A research
protocol to monitor genomic markers, neurotransmitters and hormone levels in
patients with a chronic illness receiving palliative care. The majority of
patients receiving palliative care have had ongoing bloodwork done as part of
their disease management. By comparing those samples with ongoing collection as
their disease progresses researchers are looking to identify specific chemicals
and concentrations that can be linked to changes in mood, cognition or
personality. In addition to the blood analysis a trained researcher will
collect data via a questionnaire format about how the patient perceived
themselves psychologically before disease onset and how they perceive
themselves currently. Care givers and close family or friends would also be
invited to complete the questionnaire to give an objective view of the same. A
control group of patients with the same disease states who are diagnosed as
stable or in remission would also be asked the same questions and agree to a
blood test at Day 1 and Day 120 to look for biomarker changes.
Research Ethics
For robust data,
cohorts should aim for 200-300 each. All participants will be randomized with
no identifying information on either the samples of questionnaires, and the key
to the randomization will be held at a separate location in a secure manner.
Participants may elect to end their participation at any time for any reason.
This will be a non-financially compensated study and participants informed that
it will not provide any medical advantage or cure for them, but the information
gathered could be used to help others with the same disease in the future. The
Protocol will be reviewed by the Institutional Review Board (IRB) of the
researcher’s primary institution as well as any Ethics Review Board or IRB of
the patient’s primary doctor or palliative care facility.
The field of Psychology
has an unfortunate history of not always conducting studies to the highest
possible standard of ethics, at least by today’s standards. Studies such as
Project MKUltra, Stanford Prison Experiment, Baby Albert or the Pit of Despair
would not be condoned, or allowed, under current guidelines. However, it may be
said of current trials today that they crossed ethical lines when they are
reviewed 100 years from now. The best researchers can do is to function not
just within the Best Practices of any given field, but strive to rise a step
above. For some people the idea of asking a person entering Hospice to
participate in any clinical trial could be seen as ghoulish or unethical. Based
on my experience with patients who are aware that their lifespan has been given
a finite time frame, they arrive at a mental place where they are concerned
about those around them in some ways more than they are for themselves. I think
it would not be inappropriate to ask for their participation, or unethical, as
I would not be promising them any personal or financial benefit.
Research and Informed Ethics
My
understanding is that within this group of students, I am the only one with
actual real-life experience working with a Clinical Trial team for
Pharmaceutical or Medical Device companies. As such I have not only helped
create Clinical Trial Protocols, but worked with the teams to train the
clinical investigators, tracked IRB approvals, collected data, verified
randomization and ensured no subject identifying data was present on those
records. As part of my duties I attended company Ethics training every year
along with re-training on Title 21 of the Code of Federal Regulations (21 CFR).
There are specific sections that address the requirements for the Food and Drug
Administration (FDA), the Drug Enforcement Agency (DEA) and the Office of
National Drug Control Policy (ONDCP).
I have participated in
several FDA Audits, most which were routinely scheduled to assure the
regulatory agency that our records were in compliance and there were no
violations of law, regulations or ethics. I also experienced the type of audit
no company wants to face – a surprise visit from a uniformed, and armed, FDA
Auditor responding to serious failures of procedure. In the late 1990s I was
part of a team working for American Home Products when our records were seized due
to a court order by County Sheriffs as part of the fenfluramine / phentermine, usually
called fen-phen, court case that arose from improper use of these drugs
that resulted in the death of one women and hundreds of cases of serious
cardiac disease.
So, my awareness of
ethics in research along with medical and clinical trials is not the result of
this course alone, or my current literature reviews. It was learned working
side by side with Investigators, FDA Liaisons and one-the-job training. In
fact, my view of bio-ethics are more narrowly focused than even some of my
former colleagues who were willing to push the regulations “just a little” to
save money on a larger and more costly study. I am not willing to fudge the
regulations at all, I have seen the damage it can do to not only participants,
but to a company or team who are trying to do the right thing and help people.
Being willing to shut down an experiment
entirely, put it on hold or draft a significant re-write should not be
something we take lightly, nor should these steps be set aside in order to meet
an arbitrary deadline or budget. For what does it benefit Society as whole if a
research team is exposed to pressure based on Investor expectations to cut
corners and hold off on reporting serious adverse events just to complete a
cohort? Or senior leadership ignores your progress notes telling them that
documentation is not being properly completed and signed, which leaves us open
to reprimand by regulatory agencies for not even following our own internal
policies and procedures.
These are just a few of the actual
occurrences I and my teams faced, which ultimately led me to leave the industry
in search of a better way to make a positive difference in a patient’s life.
Sources
An, C. (29 Jul 2018). Neuroprosthetics –
A Simple Guide from a Neuroscience Student. Retrieved from: https://medium.com/neurotechx/neuroprosthetics-a-simple-guide-from-a-neuroscience-student-7264740c10d3
Andrewes, H. E., Drummond, K. J.,
Rosenthal, M., Bucknill, A., & Andrewes, D. G.
(2013). Awareness of psychological and relationship problems amongst brain
tumour patients and its association with carer distress. Psycho-Oncology, 22(10),
2200–2205. Retrieved from https://search-ebscohost-com.ezproxy. snhu.edu/
login.aspx ? direct =true&db =psyh & AN =2013-35253-008&site=eds-live &
scope = site
(2013). Awareness of psychological and relationship problems amongst brain
tumour patients and its association with carer distress. Psycho-Oncology, 22(10),
2200–2205. Retrieved from https://search-ebscohost-com.ezproxy. snhu.edu/
login.aspx ? direct =true&db =psyh & AN =2013-35253-008&site=eds-live &
scope = site
Avegno, E.M., Sailing, M.D., Borgkvist, A., Mrejeru,
A., Whitebirch, A.C.,
Margolis, E.B., Sulzer, D. & Harrison, N.L. (Nov 2016). Voluntary adolescent
drinking enhances excitation by low levels of alcohol in a subset of
dopaminergic neurons in the ventral tegmental area. Neuropharmacoloty.
110(A), 386-395. https:// doi.org/ 10. 1016/ j.neuropharm.2016.07.031
Margolis, E.B., Sulzer, D. & Harrison, N.L. (Nov 2016). Voluntary adolescent
drinking enhances excitation by low levels of alcohol in a subset of
dopaminergic neurons in the ventral tegmental area. Neuropharmacoloty.
110(A), 386-395. https:// doi.org/ 10. 1016/ j.neuropharm.2016.07.031
Azabou, E., Fischer, C., Guerit, J.,
Annane, D., Mauguiere, F., Lofaso, F. & Sharshar, T.
(2017). Neurophysiological assessment of brain dysfunction in critically ill
patients: an update. Neurological Sciences, 38(5), 715–726. https://doi-
org.ezproxy. snhu.edu/ 10. 1007 / s10072-017-2824-x
(2017). Neurophysiological assessment of brain dysfunction in critically ill
patients: an update. Neurological Sciences, 38(5), 715–726. https://doi-
org.ezproxy. snhu.edu/ 10. 1007 / s10072-017-2824-x
Burkauskas, J., Bunevicius, A.,
Brozaitiene, J., Neverauskas, J., Lang, P., DuWors, R.,
Mickuviene, N., & Bunevicius, R. (Jan 2017). Cognitive Functioning in Coronary
Mickuviene, N., & Bunevicius, R. (Jan 2017). Cognitive Functioning in Coronary
Artery Disease Patients: Associations
with Thyroid Hormones, N-Terminal Pro-B-
Type
Natriuretic Peptide and High-Sensitivity C-Reactive Protein. Archives of
Clinical
Neuropsychology. 32(2). DOI: 10.1093/arclin/acx004.
Chemo-brain among women with breast
cancer is pervasive, study shows. (2017). Women’s
Health Weekly, 31.
Cropley, V. L., Fujita, M.,
Bara-Jimenez, W., Brown, A. K., Zhang, X.-Y., Sangare, J., Herscovitch P.,
Pike, V. W., Hallett, M., Nathan, P. J. & Innis, R. B. (Jul 2008). Pre- and
post-synaptic dopamine imaging and its relation with frontostriatal cognitive
function in Parkinson disease: PET
studies with [¹¹C]NNC 112 and [¹⁸F] FDOPA. Psychiatry Research:
Neuroimaging, 163(2), 171–182. https://doi-org.ezproxy.snhu.edu/10.1016/j.pscychresns.2007.11.003
DiNicolantonio, J., O'Keefe, J. & Wilson, W. (Aug
2017). Sugar addiction: Is it real? A narrative review. British Journal of
Sports Medicine. 52. bjsports-2017. 10.1136/bjsports-2017-097971.
Feinkohl, I., Sattar, N., Welsh, P., Reynolds,
R. M., Deary, I.J., Strachan, M.W. & Price,
J.F. (04 Sep 2012). Association of N-Terminal Pro-Brain Natriuretic Peptide with
Cognitive Function and Depression in Elderly People with Type 2 Diabetes. PLOS
ONE, 7(9). https://doi-org.ezproxy. snhu.edu/ 10.1371/ journal. pone. 0044569.
J.F. (04 Sep 2012). Association of N-Terminal Pro-Brain Natriuretic Peptide with
Cognitive Function and Depression in Elderly People with Type 2 Diabetes. PLOS
ONE, 7(9). https://doi-org.ezproxy. snhu.edu/ 10.1371/ journal. pone. 0044569.
Gorissen, S. H. M.,
Rémond, D., & van Loon, L. J. C. (2015). The muscle protein synthetic
response to food ingestion. Meat
Science, 109, 96–100. https://doi-org.ezproxy.snhu.edu/10.1016/j.meatsci.2015.05.009
Guendelman,
S., Medeiros, S., & Rampes, H. (2017). Mindfulness and Emotion Regulation:
Insights from Neurobiological, Psychological, and Clinical Studies. Frontiers
in psychology, 8, 220. doi:10.3389/fpsyg.2017.00220
Kantor, J. R. (1963).
Aristotle: Institutor of Biopsychology. In The scientific evolution of
psychology, Vol I. (pp. 116–151).
Principia Press. https://doi-org. ezproxy. snhu. edu/10.1037/11183-009
Kellehear, A. (2017). Unusual
perceptions at the end of life: limitations to the diagnosis of
hallucinations in palliative medicine. BMJ Supportive & Palliative Care, 7(3),
238–246. https://doi-org.ezproxy.snhu.edu/10.1136/bmjspcare-2015-001083
hallucinations in palliative medicine. BMJ Supportive & Palliative Care, 7(3),
238–246. https://doi-org.ezproxy.snhu.edu/10.1136/bmjspcare-2015-001083
Kyota, A., & Kanda, K. (2019). How
to come to terms with facing death: a
qualitative study examining the experiences of patients with terminal
Cancer. BMC Palliative Care, 18(1), 33. https://doi-org.ezproxy.snhu.edu.
/10.1186/s12904-019-0417-6
qualitative study examining the experiences of patients with terminal
Cancer. BMC Palliative Care, 18(1), 33. https://doi-org.ezproxy.snhu.edu.
/10.1186/s12904-019-0417-6
Netter, P. (2001). Biopsychology and
Health. International Encyclopedia of Social & Behavioral Sciences,
1226–1231. https://doi-org.ezproxy.snhu.edu/10.1016/B0-08-043076-7/03781-5
No comments:
Post a Comment