An Integrated Review Of Psychological Stress In Parkinsons Disease: Biological Mechanisms And Symptom And Health Outcomes
Kim Wieczorek Austin
1Virginia Commonwealth University School of Nursing, 1100 East Leigh Street, Richmond, VA 23219, USA
2Virginia Commonwealth University Parkinsons and Movement Disorders Center and VCU Health Neuroscience, Orthopaedic, and Wellness Center, 11958 West Broad Street, Richmond, VA 23233, USA
The unpredictable and debilitating nature of the symptoms associated with PD combined with the inability to halt or slow disease progression has the potential to result in psychological stress. Psychological stress is a complex phenomenon that involves cognitive, emotional, behavioral, and biological responses to events or experiences that are perceived as threatening . An individuals ability to cope with and adapt to psychological stress can be influenced by the number and significance of stressful events experienced within a given period of time, the degree to which stressors are perceived as threatening or harmless, and biological responses designed to promote adaptation . The inability to cope with or adapt to psychological stress has been associated with poorer symptom and health outcomes that may be relevant in PD. For example, in non-PD populations, significant relationships have been demonstrated between psychological stress and increased motor symptomology , pain , fatigue, , cognitive decline , and functional disability .
3. Results and Discussion
Dyskinesia Cause #: Too Much Medication
Each person with Parkinsons experiences symptoms a little differently than the next. The challenge for the physician is finding the dose and formulation of levodopa that provides the right balance of symptom relief while avoiding dyskinesia, says Todd Herrington, MD, PhD, a neurologist at Massachusetts General Hospital in Boston and an instructor in neurology at Harvard Medical School in Cambridge, Massachusetts. Too much levodopa can trigger dyskinesia and possibly make other Parkinsons symptoms worse, he says. But if people dont take enough medication, it can leave them feeling slow, stiff, and even trapped in their own body. So be sure to work with your doctor on the right treatment regimen for you.
Top Medicines That Worsen Parkinsons Disease Or Cause Secondary Parkinsonism
Medications to avoid
Some medications can worsen movement symptoms of PD, including slowness, stiffness, tremor and dyskinesia. These drugs, listed below, are used to treat psychiatric problems such as hallucinations, confusion or gastrointestinal problems, such as nausea. The stress of your illness, hospital stay or new medicines can increase your risk of hallucinations while hospitalized. Common anti-hallucination medicines to be avoided are listed by generic or chemical name followed by the trade name.
Anti-hallucination medicines to avoid
Note: the anti-hallucination medicines Quetiapine or Clozapine can be used. The following should be avoided:
- aripiprazole , chlorpromazine , flufenazine , haloperidol , molindone , perphenazine , perphenazine and amitriptyline , risperidone , thioridazine , thiothixene
Anti-nausea medicines to avoid
- metoclopramide , phenothiazine , promethazine
Medicines to avoid if you are on Rasagiline or Selegiline
- Pain medicines Meperidine , Tramadol ,Antispasmodic medicine Flexeril , Dextromthorphan and St Johns Wort.
- This is not a complete list of medicines to avoid. If you have questions about other medications, ask your pharmacist or doctor.
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Reviewanxiety: An Ignored Aspect Of Parkinsons Disease Lacking Attention
Anxiety is a neuropsychiatric complication of Parkinsons disease .
Anxiety has been given less attention while treating PD.
Management of anxiety is crucial to improve quality of life of the affected patients.
Use of complementary based medicines could be beneficial.
Alternative approaches will lead to novel therapeutic treatment for PD and various complications associated with it.
Stress Factors In Parkinson’s
It is not unusual to feel stressed most of us succumb to it at various times – but there are a number of reasons why stress worsens Parkinsons symptoms, such as tremor, slow movement, freezing, speech and swallowing difficulties.
A diagnosis of Parkinsons can lead to stress as it brings with it worries and uncertainties about the future, both for you and your family.
Dopamine, which is deficient in the brains of people with Parkinsons, is used by the body to produce adrenaline. Adrenaline needs to be produced in order for the body to cope with stress. It is therefore not surprising that people with the condition do not produce adequate adrenaline to cope with physical, mental or emotional stress under control.
Analysing and addressing the reasons for stress and learning to relax is important in managing symptoms and maintaining a good quality of life. With the right attitude, careful planning and lifestyle adjustments many sources of stress can be eliminated or their impact reduced.
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Why Are Parkinsonian Symptoms Worse In The Morning
Most patients with advanced Parkinsons disease experience fluctuating symptoms, known as ON and OFF episodes, when they take medications such as carbidopa/levodopa. When you first take a dose, you may experience an ON episode where you are energetic and able to move around freely. OFF episodes can occur when you’re waiting for your next dose of medication, resulting in a marked decline in physical ability and a returning of symptoms.
Some people find that Parkinsonian symptoms are worse in the morning. The medical term for the daytime worsening of Parkinsonian symptoms is morning akinesia,” affecting around 60% of Parkinsons patients. OFF episodes occur when levodopa medications become less effective over time, resulting in motor fluctuations. These periods usually start first thing in the morning after a treatment-free night.
Are Some People More Prone To Anxiety Than Others
Some people are more prone to problematic anxiety than others it can be a feature of our personality. Higher levels of anxiety also have a strong genetic component. This means that if our parents were anxious, we are more likely to grow up being anxious ourselves. Also, situations that drive our anxiety can be learned. If we grow up with someone who is anxious about lots of things, and tends to cope by avoidance and worry, we can learn these same traits.
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Stage One Of Parkinsons Disease
In stage one, the earliest stage, the symptoms of PD are mild and only seen on one side of the body , and there is usually minimal or no functional impairment.
The symptoms of PD at stage one may be so mild that the person doesnt seek medical attention or the physician is unable to make a diagnosis. Symptoms at stage one may include tremor, such as intermittent tremor of one hand, rigidity, or one hand or leg may feel more clumsy than another, or one side of the face may be affected, impacting the expression.
This stage is very difficult to diagnose and a physician may wait to see if the symptoms get worse over time before making a formal diagnosis.
Depression And Parkinsonism In An Animal Model Of Neurodegeneration
Early post-natal maternal separation is widely used to create an animal model that exhibits some depressive/anxiety-like behaviors . This established model of depression is useful to study 6-OHDA lesion of the medial forebrain bundle to lesion nigrostriatal DA neurons. We recently investigated the antiparkinsonian effects of Fluvoxamine maleate in a parkinsonian rat model of neurodegeneration associated with anxiety/depressive-like behaviors . Although these studies were a small exploratory open-label trial, they anticipated outcomes on a larger double-blind placebo-controlled study that include non-depressive animals with Parkinsonism. Fluvoxamine maleate treatment has shown potential in decreasing dopaminergic neuronal loss as well as potential to regulate neuronal pro- and anti-inflammation markers in the striatum . Therefore, a combined animal model of chronic stress-induced depression with a 6-OHDA lesioned parkinsonian animal model is an appropriate model to investigate the relationship between depression and PD. This association suggests that the stressor needs to be applied prior to the injection of the neurotoxin 6-OHDA to combine depressive-like behaviors with a potential risk of developing motor-symptoms that characterize Parkinsonism. This combination showed the double advantage of investigating a non-motor symptom as part of an early onset of PD together with the neuroprotective effects of a treatment on the development of the disease.
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Anxiety And Parkinsons Research
What does this finding mean for the future of diagnosis or treatment of Parkinsons? Ongoing research is compelling, says Pontone. Part of what we are doing is looking at anxiety disorders that occur long before the onset of Parkinsons to see if there are characteristics that may differentiate that anxiety or predict an increased risk of Parkinsons disease.
Meanwhile, because theres an established link between anxiety and Parkinsons disease, patients and their families should be upfront with their doctors about anxiety symptoms. Behavioral therapy and medications for example, anti-anxiety meds or antidepressants can effectively treat anxiety disorders. Theres no need for anyone to suffer in silence.
Targeting Parkinsons-Linked Protein Could Neutralize 2 of the Diseases Causes
Researchers report they have discovered how two problem proteins known to cause Parkinsons disease are chemically linked, suggesting that someday, both could be neutralized by a single drug designed to target the link.
Why Is There A Need For A New Approach To Managing Anxiety
One disadvantage of CBT is that it can be hard to access for some people and involves a considerable time commitment over a period of months. While not necessarily replacing CBT, we are looking for other simpler treatments that people may be able to use on their own via a computer, tablet or smart-phone, and that can be done over a period of weeks rather than months. Our current research is examining the potential of one such approach to see if it is worth developing further.
Parkinsons UK have awarded Richard and his team £44,196 to investigate interpretation bias and anxiety in people with Parkinsons.
Previous research has shown that people who are anxious have a tendency to interpret situations as more dangerous or threatening than they actually are.For example, imagine you see a friend across the street and they do not wave. An anxious person may worry that the friend is upset about something they did a negative interpretation, rather than assuming the friend did not see them a neutral interpretation. This negative interpretation bias can trigger feelings of anxiety and, in this scenario, may cause the person to worry about the event or avoid the friend.
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Perceived Effects Of Stress In Pd Patients
Scatterplots in Fig. show that patients who perceived high levels of stress , typically ruminated more , perceived lower quality of life , had low levels of self-compassion and scored lower on dispositional mindfulness . Furthermore, these highly stressed patients perceived higher daily life disease severity . The association between perceived stress and disease duration in the PD group was very small . All correlations were significant .
Fig. 1: Determinants of perceived stress in Parkinsons disease.
This figure shows the relation between perceived stress as measured by the Perceived stress Scale and a quality of life measured with the Parkinsons Disease Questionnaire , n=3009 b dispositional mindfulness measured with the Five Facet Mindfulness Questionnaire , n=2899 c rumination measured with the Ruminative Response Scale , n=2899 and d self-compassion measured with the Self Compassion Scale , n=2899 . For the PDQ-8, we have reversed the scores , such that for each of the variables shown a higher score means a higher subjective rating. For every plot, the Pearson correlation is shown with the associated 2-tailed significance.
If applicable, patients could complete other strategies they had to reduce stress in free text fields. Frequently mentioned were religion , music , reading , art/creativity , anxiolytic/antidepressant medication , and looking for social support .
Cholinesterase Inhibitors Widely Used To Treat Dementia
Cholinesterase inhibitors, widely used to treat dementia, may cause worsened parkinsonism, primarily increased tremor . Large double-blind trials of rivastigmine, a cholinesterase-inhibiting drug, in both dementia with Lewy bodies and Parkinson disease dementia have demonstrated that rivastigmine is well tolerated without significant worsening of motor function overall, although tremor may increase . The other cholinesterase inhibitors have been less well studied but appear to have similar benefits and side effects.
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Oxidative Stress Neuroinflammation And Parkinsons Disease
Oxidative stress is the result of an imbalance between the production of reactive oxygen species and the body capacity to counteract their harmful effects through neutralization by antioxidant defenses . Brain neurons are constantly exposed to reactive oxygen species and reactive nitrogen species as a result of endogenous or exogenous exposure to oxidative stress . Chronic psychological stress increases neuroinflammation which may facilitate nigral cell death in PD . For instance, under stress conditions, there is evidence that dysfunction of inflammatory markers such as tumor necrosis factor -, interleukin -1, IL-6, IL-10, transforming growth factor – in microglia of patients with depression participates in worsening PD symptoms .
PD research is often directed towards the prevention of DA neuron degeneration . However, all current treatments only address the symptomatic effects of the disease, none of which neither halt nor retard DA neuron degeneration . About 95% of PD cases are sporadic hence caused by environmental factors versus 5% that are inherited . The point of view in favor of exposure to stressful events early in life predisposing an individual to develop neurodegenerative disorders later in life seems to emphasize that PD is much more than just a DA-dependent motor deficit.
Why Do Off Episodes Happen During The Day
There are various reasons why you might experience OFF episodes in the morning or during the day. A period is termed an OFF episode when levodopa plasma concentration decreases, causing the medication to wear off temporarily and symptoms to return. According to a 2011 study, daytime OFF episodes reflect the natural dopaminergic decline with insufficient nighttime storage of the dopaminergic system during sleep.
In other words, your body naturally struggles to produce dopamine at night, which leads to inadequate stores of dopamine during the day. As we know, it is primarily the loss of dopamine cells in the brain that causes PD motor symptoms, and this is what levodopa/carbidopa intends to treat. Unfortunately, the medication stops being as effective over time , causing patients to experience more OFF than ON episodes. Daytime worsening of Parkinsonian symptoms can also be caused by nighttime stress or sleep disturbances in Parkinson’s patients.
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Serotonin Hypothesis Of Depression
Serotonin is mainly produced in the dorsal raphe nucleus . Serotonin transporters take up released serotonin from the synaptic cleft into serotonergic neurons in a manner that helps to modulate various functions in the brain including mood and emotion . The striatum, the amygdala, and the prefrontal cortex are regions of the brain that are innervated by serotonergic neurons . These brain regions including the dorsal raphe nucleus which is part of the brains serotonergic system, are activated during early maternal stress . Abnormal 5-HT levels in these brain areas have been associated with depression . Pre-clinical and clinical studies have demonstrated that early life stress affects 5-HT levels in the brain and this may lead to depression . Selective serotonin re-uptake inhibitors are a class of antidepressant drugs commonly used to treat depression . SSRIs work by blocking 5-HT re-uptake thus increasing the availability of 5-HT in the synaptic cleft as well as its chance to bind to receptors in the post-synaptic membrane . Therefore, by restoring the levels of monoamines and their transporters in the brain, SSRIs drugs are appropriate treatments to address early life stress dysfunction that predisposes to depression later in life.
Q: Are There Any Studies Of The Effects Of The Covid
A: Currently, there is no data that the COVID-19 vaccine has any long-term negative effects on anyone, including those with PD. Some people with PD have reported a worsening of PD symptoms in the short term after vaccination, which then resolve. The Center for Disease Control instituted a vaccine safety monitoring system, called v-safe, which captures side effects of the vaccine. If you have side effects from the vaccine and have PD, you can alert the CDC using this system. This will be an invaluable tool for scientists to discover trends in vaccine side effect profiles.
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Genetic Causes Of Parkinsons Disease
Although the genetic causes of PD can only account for a few percentage of patients with genes and genetic loci dysfunctions, early stress exposures usually predispose to depression, prompt or worsen motor symptoms in PD . The genetic origin of PD mostly includes mutations in -synuclein, parkin phosphatase and tensin homologue -induced putative kinase 1 , leucine-rich repeat kinase 2 and DJ-1 genes . Mutations of these genes can result in abnormal protein accumulation, -synuclein aggregates, protein phosphorylation, mitochondrial dysfunction and oxidative stress which is the most common pathway to cell death in PD pathogenesis . As exposure to stress early in life is known to alter both the behavior and physiology in certain brain areas, it is accepted that genetic changes associated with PD are in part the result of alterations in gene expression in these brain areas also affecting the stress response system .
Dyskinesia Cause #: A High
Knowing when, and how, to take medication food can help reduce dyskinesia, says Thomas.
First, youll need to know how levodopa works in the body and how the medication interacts with food: The amino acids found in protein are used in the body and the brain, but first, these acids must pass through the blood-brain barrier the same pathway thats used by levodopa, says Dr. Poston. Because of this so-called traffic congestion, a high-protein meal can interfere with the way the medication is absorbed, worsening the on-off fluctuations that can come with levodopa therapy.
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