Neurobiological Aspects Of Stress And Depression
Appropriate responses to external or internal adversity are critical for adaptation and survival. The stress response involves the activation of multiple bodily systems, the most prominent of which are the HPA axis and autonomic nervous system. Activation of the HPA axis creates a neuroendocrine cascade that results in the elevation of glucocorticoid levels. Glucocorticoids subserve important adaptive functions during stress exposure , and also provide negative feedback regulation of HPA axis activation, thereby limiting their own secretion. While initially adaptive, protracted activation of the stress response contributes to physiological abnormalities and may be involved in the development of disease states . Mood disorders are often preceded by stressful life events, whether environmental or physiological , and chronic stress is considered an important risk factor for depression . Notably, glucocorticoid receptors are localized to many regions involved in depressive and neurological pathologies, including the prefrontal cortex , hippocampus, striatum, limbic system, nucleus accumbens, and ventral midbrain , suggesting the potential for glucocorticoids to play a role in disease processes.
Molecular and cellular effects of chronic stress
Types Of Anxiety Disorders Found In Parkinson’s Disease
Generalised anxiety disorder, panic disorder, social phobia, phobic disorder, agoraphobia, obsessive-compulsive disorder, and anxiety disorder not otherwise specified have all been identified in patients with Parkinson’s disease . The diagnoses in the patients with Parkinson’s disease appear to be clustered in the panic disorder, phobic disorder, and generalised anxiety disorder areas.
Box 1: Anxiety disorders found in Parkinson’s disease
Generalised anxiety disorder
Treatment Of Depression/anxiety Associated With Parkinsons Disease
Antidepressants are a popular treatment for moderate to severe forms of depression in PD . Several classes of antidepressants are available and they work in a slightly different way with different side-effects. Neurotransmitters are associated with the pathogenesis of depression in PD . Antidepressants relieve the symptoms of depression by targeting these neurotransmitters . Tricyclic, monoamine oxidase inhibitors and newer selective antidepressants including serotonin and noradrenaline reuptake inhibitors are classes of antidepressants known to be effective in treating depression .
Tricyclic drugs are the older version of antidepressants . This class of antidepressant includes drugs such as desipramine, doxepin, imipramine, trimipramine . Although tricyclic antidepressant drugs are effective in treating depression, they have several side effects such as dry mouth, constipation, difficulty urinating, sedation, weight gain or sexual problems . Also, tricyclic drugs can be fatal in overdosing .
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Environmental Toxins And Parkinsons Disease
Neuronal cell death in PD may also be triggered by exposure to toxic substances or environmental factors which precipitate the symptoms of the disease as they render the brain vulnerable to subsequent physiological chronic stress . The environmental cause of PD mainly refers to exposure to dopaminergic toxins 6-hydroxydopamine , 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine , paraquat and rotenone as these toxins are known to induce formation of reactive oxygen species and oxidative stress which may result in neuronal cell death .
DA is one of the common neurotransmitters present in most parts of the central nervous system . The mesocortical, mesolimbic, nigrostriatal and tubero-infundibular pathways are the four main pathways that play a key role in dopaminergic signaling . DA cannot cross the blood brain barrier, therefore, it is synthesized from tyrosine which is carried into the brain via amino acid transporters . At the dopaminergic neuron level, tyrosine is then converted into dihydroxyphenylalanine by tyrosine hydroxylase then finally into DA by aromatic L-amino acid decarboxylase . DA is then stored in the vesicle until an action potential allows the vesicle to be discharged into the synapse . Monoamine oxidase is the enzyme that is responsible for breaking down excess DA and is known to similarly act on 6-OHDA inducing oxidative stress resulting in apoptosis .
What Is The Outlook For Persons With Parkinsons Disease
Although there is no cure or absolute evidence of ways to prevent Parkinsons disease, scientists are working hard to learn more about the disease and find innovative ways to better manage it, prevent it from progressing and ultimately curing it.
Currently, you and your healthcare teams efforts are focused on medical management of your symptoms along with general health and lifestyle improvement recommendations . By identifying individual symptoms and adjusting the course of action based on changes in symptoms, most people with Parkinsons disease can live fulfilling lives.
The future is hopeful. Some of the research underway includes:
- Using stem cells to produce new neurons, which would produce dopamine.
- Producing a dopamine-producing enzyme that is delivered to a gene in the brain that controls movement.
- Using a naturally occurring human protein glial cell-line derived neurotrophic factor, GDNF to protect dopamine-releasing nerve cells.
Many other investigations are underway too. Much has been learned, much progress has been made and additional discoveries are likely to come.
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What Are The Symptoms Of Parkinsons Disease Anxiety
Depression and anxiety with or without Parkinson’s disease can be debilitating. You may suffer from a “loop” of anxious thoughts about your illness or the future, or you may find yourself experiencing panic attacks or feeling afraid to go outside. You may also have a negative view of the world and your place in it.
While it’s normal to feel some degree of worry when you are diagnosed with Parkinson’s disease, persistent anxiety that doesn’t go away when you relax may require treatment. Here are some of the most common Parkinson’s disease and anxiety symptoms:
- Constant feelings of worry or dread
- Panic attacks characterized by heart palpitations, sweating, nausea and lightheadedness
- Feeling out of control or helpless
- Long, intense periods of unease
- Feeling unsafe for in normal situations
- Wanting to isolate yourself or being afraid to leave the house
- Avoiding certain situations because they trigger anxiety
Noradrenaline Hypothesis Of Depression
Noradrenaline is known to play a role in the regulation of emotions . The deficiency of noradrenaline/norepinephrine mainly produced in the locus coeruleus and affecting certain brain areas such as the prefrontal cortex, the hippocampus or the hypothalamus has been associated with depression . Studies have shown that exposure to chronic stress including early maternal separation decreases noradrenaline levels within the brain leading to depression . This explains why selective norepinephrine re-uptake inhibitors , a new class of antidepressants that work by increasing norepinephrine levels in the brain, have been used to treat depression .
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How Is Parkinsons Disease Diagnosed
Diagnosing Parkinsons disease is sometimes difficult, since early symptoms can mimic other disorders and there are no specific blood or other laboratory tests to diagnose the disease. Imaging tests, such as CT or MRI scans, may be used to rule out other disorders that cause similar symptoms.
To diagnose Parkinsons disease, you will be asked about your medical history and family history of neurologic disorders as well as your current symptoms, medications and possible exposure to toxins. Your doctor will look for signs of tremor and muscle rigidity, watch you walk, check your posture and coordination and look for slowness of movement.
If you think you may have Parkinsons disease, you should probably see a neurologist, preferably a movement disorders-trained neurologist. The treatment decisions made early in the illness can affect the long-term success of the treatment.
Lack Of Exercise/physical Activities
The idea that exercise might have a role in Parkinsons disease is not new. Researchers have been trying to find a connection between Parkinsons and exercise for many years. They think that those who do regular exercise are less likely affected by the disease than those who dont.
A study published in the Journal of Neurology suggests that higher levels of physical activity may reduce the risk of developing Parkinsons disease. In this study, 125,828 provided information on physical activity in early adulthood. During the follow-up, a total of 387 Parkinsons cases were identified. The study found that the people who didnt develop the disease were mostly involved in some sort of higher levels of physical activity.
Similarly, one meta-analysis that included data from 8 prospective studies has concluded that moderate to vigorous physical activity may have an inverse relationship with a risk of Parkinsons.
Although it is not known how exercise could protect someone from developing Parkinsons, researchers think that it may inhibit abnormal changes in dopamine neurons and contribute to the healthy functioning of brain parts involved in body movement.
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How Do You Care For Someone With Dementia
Caring for a patient with vascular dementia can be a challenging experience. But there are ways to make things a little easier for both you and your loved one:
- Establish a routine. A calm environment can reduce worry and agitation, which in turn helps the person cope with their dementia. Establishing a daily routine that includes comfortable activities can help create this calm environment and take some pressure off you as well.
- Help them with cognitive rehabilitation. If your loved one struggles with memory or attention, they may not do cognitive rehab on their own. Instead, you may need to help them with their exercises. If this becomes too frustrating, remember to take care of yourself too.
- Find a support group. Caring for someone with post-stroke dementia can be a full-time job, and this can lead to social isolation. Support groups put you in touch with people going through the same experiences and give you a network you can rely on for help and advice.
- Take time for yourself. To avoid caregiver burnout, its important to take time to care for your own needs. If possible, have another family member take over your caregiving duties for the day and allow yourself time to recharge.
Following these tips can help lighten the burden a little and make the caregiving process smoother.
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Anxiety And Antiparkinsonian Medications
There is no consensus on whether antiparkinsonian medications are responsible for symptoms of anxiety in Parkinson’s disease.
Stein et al found that the levodopa dose was similar in anxious and non-anxious patients. Hendersonet al noted that 44% of patients with Parkinson’s disease noticed anxiety symptoms before starting levodopa. Menza et al found that the levodopa dose did not significantly correlate with anxiety levels: they suggested that anxiety in patients with Parkinson’s disease is unlikely to be a side effect of levodopa treatment. In contrast, Vasquez et al found that panic attacks were related to levodopa therapy but not to other agonist drugs.
Lang reported anxiety in five of 26 patients when pergolide was added to their treatment regimen. Menza et al found no differences in measures of anxiety in patients receiving or not receiving pergolide. Menzaet al found no differences in measures of anxiety in patients receiving or not receiving selegeline.
The temporal relationship between panic attacks and off periods have led some authors to suggest that panic attacks may be related to falling brain levodopa levels. Anxiety fluctuations may be an important component of levodopa induced fluctuations. In a double blind placebo controlled trial, Maricle et al found that anxiety levels fell and motor performance improved during a levodopa infusion.
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Beat Stress And Parkinsons Disease With Exercise
In healthy cells, there is a balance between the production of free radicals called reactive oxygen species and the antioxidants that neutralize them. Oxidative stress occurs when there is an increase in the number of ROS compared to antioxidants. Psychological stress can contribute to these imbalances. Even acute bouts of high stress can negatively affect brain health, as the resulting increase in oxidative stress causes a host of inflammatory processes within neurons .
These changes are similar to some of the issues that already occur with Parkinsons disease, where there is an increase in oxidative stress in neurons that produce dopamine in the substantia nigra. Additionally, damaged mitochondria within these neurons dont get tagged correctly to be discarded, leading to further increases in oxidative stress, inflammation and damage. Compounding the effects of stress with the processes of Parkinsons disease can lead to a toxic environment and degeneration within key parts of the brain .
Now more than ever is a time to prioritize your self-care. Life is stressful, especially while also managing difficult disease. One of the best ways we can support our body in times of stress is engaging in regular movement. Happy exercising!
Parkinsons Disease And Stress
Stress may play a role in the development of PD. The principle risk factor for PD is aging, which may also be associated with elevated levels of cortisol . Cortisol is also elevated in PD patients compared to healthy age-matched controls . Acute treatment with levodopa can reduce plasma cortisol levels in PD patients , suggesting a connection between dopamine hypofunction and HPA axis hyperactivity. Stressful life events may also precipitate the development of PD. For example, prisoners of war had a much higher incident rate of PD development thirty-five years after release . Emotional stress can transiently increase motor symptoms , consistent with acute effects on nigrostriatal function. Appearance of the clinical PD symptoms during a stressful period may reflect damage to the nigrostriatal system that had been masked during the preclinical stage . Loss of mesocortical dopamine neurons, which occurs in more advanced stages of PD, may result in the system becoming more vulnerable to stress, as dopamine release in the cortex inhibits stress-activated neurons in the nucleus accumbens . Individuals with PD also have reduced hedonic responses after exposure to emotional stress, but stress did not affect the selected motor symptoms studied .
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Is Parkinsons Disease Inherited
Scientists have discovered gene mutations that are associated with Parkinsons disease.
There is some belief that some cases of early-onset Parkinsons disease disease starting before age 50 may be inherited. Scientists identified a gene mutation in people with Parkinsons disease whose brains contain Lewy bodies, which are clumps of the protein alpha-synuclein. Scientists are trying to understand the function of this protein and its relationship to genetic mutations that are sometimes seen in Parkinsons disease and in people with a type of dementia called Lewy body dementia.
Several other gene mutations have been found to play a role in Parkinsons disease. Mutations in these genes cause abnormal cell functioning, which affects the nerve cells ability to release dopamine and causes nerve cell death. Researchers are still trying to discover what causes these genes to mutate in order to understand how gene mutations influence the development of Parkinsons disease.
Scientists think that about 10% to 15% of persons with Parkinsons disease may have a genetic mutation that predisposes them to development of the disease. There are also environmental factors involved that are not fully understood.
Multiple Sclerosis Vs Parkinsons Disease: Us Prevalence And Economic Impact
Anyone can develop multiple sclerosis, but it mostly affects 20- to 40-year-olds. Prevalence of multiple sclerosis in the U.S. is estimated at over 400,000 cases, and nearly 200 new cases are diagnosed each week. Rates of multiple sclerosis are highest in areas furthest away from the equator, so the rates are higher in the Northern U.S.
Direct and indirect costs resulting from multiple sclerosis can range from $8,528 to $54,244.
One million Americans live with Parkinsons disease. The average cost of Parkinsons disease including treatment, lost work wages, and social security payments is $25 billion annually in the U.S.
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Strategies To Help You Manage These Feelings
- Talk to someone about how you feel. This is one way to get these feelings out into the open. Talk to a close friend, a family member or someone with whom you feel comfortable.
- Meet with other people who live with dementia. Together, you can share your feelings and experiences and offer each other social and emotional support.
- Contact your local Alzheimer Society to see if there is a support group in your area. If not, you may be interested in helping the Society start one. Another option may be to have the Society get you in touch with someone who can provide one-on-one support.
- Recognize that each of us has our own way of dealing with our feelings. The important thing is to find a way or ways of coping with these emotions that makes you feel better.
- Listen to what other people living with dementia suggest. When we asked the same people who shared their reactions and feeling how they coped with their emotions, hereâs what they said:
- âAcknowledge it.â
- âTake one day at a time.â
- âJoin a support group. The more you speak, you get a load off your chest.â
- âBe with people you can laugh with.â
- âGo for a walk with someone.â
- âDonât be shy. Ask for help.â
- âTell people if they hurt your feelings.â
- âAnimals are good for people. Animals are calming.â
- âDonât stay enclosed, isolated. Get out.â
- âNever give up hope. Living is worth it.
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Other Causes Of Parkinsonism
“Parkinsonism” is the umbrella term used to describe the symptoms of tremors, muscle rigidity and slowness of movement.
Parkinson’s disease is the most common type of parkinsonism, but there are also some rarer types where a specific cause can be identified.
These include parkinsonism caused by:
- medication where symptoms develop after taking certain medications, such as some types of antipsychotic medication, and usually improve once the medication is stopped
- other progressive brain conditions such as progressive supranuclear palsy, multiple systems atrophy and corticobasal degeneration
- cerebrovascular disease where a series of small strokes cause several parts of the brain to die
You can read more about parkinsonism on the Parkinson’s UK website.
Page last reviewed: 30 April 2019 Next review due: 30 April 2022
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