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.
Emerging Therapies In The Parkinsons Disease Treatment Market
Some pharmaceutical and biotech companies like Prevail Therapeutics, Axovant Gene Therapies, Neurocrine Biosciences/Voyager Therapeutics, Denali Therapeutics, International Stem Cell Corporation, Living Cell Technologies,Addex Pharma, Annovis Bio Inc, Pharma Two B Ltd, AbbVie, Prevail Therapeutics, Axovant Gene Therapies, Denali Therapeutics, Neurocrine Biosciences, and others are researching new therapies that target other aspects of Parkinsons disease pathology, namely genetic mutations, and Lewy bodies .
Drug Giants Working in the Parkinsons Disease Treatment Landscape
The expected launch of novel and emerging therapies will impact the in the upcoming years, few of them are mentioned below-
Atuzaginstat/ COR388 is an investigational therapy by Cortexyme. It is a Lysine gingipain inhibitor which is being evaluated for degenerative diseases including Alzheimers and Parkinsons Disease. It was announced that Atuzaginstat would to be studied in the PEAK trial, a new Phase II study for PD. It has begun study start-up activities. Cortexyme is targeting a specific, infectious pathogen found in the brain and other organs and tied to degeneration and inflammation in humans and animal models.
There are several other drugs in the Parkinsons Disease pipeline which includes therapies such as ABBV-951 by AbbVie, THN102 by Theranexus, and many others that will fuel the Parkinsons Disease market in the coming years.
Ratings Of Affective Pictures
One explanation for the attenuated startle effect is that negative pictures were viewed as less aversive or arousing by the Parkinsons disease group. To address this possibility, we examined subjective ratings of the pictures. shows the mean valence and arousal ratings across the unpleasant, pleasant and neutral pictures. These ratings were analysed in separate Group × Affect ANCOVAs, using age and gender as covariates. Results of the valence analysis revealed a significant main effect for Affect . Both the Parkinsons disease and the control groups rated the pictures with unpleasant contents as more negative than the neutral pictures . In turn, neutral pictures were rated as more negative than pleasant pictures . There were no differences between the disease and control groups in these valence ratings (i.e. non-significant Group effect and non-significant Group × Affect interaction .
Table 2
For arousal ratings, a significant main effect for Affect occurred. As expected, both types of emotional pictures were rated as more arousing than the neutral pictures . There were no differences in arousal ratings between the pleasant and unpleasant pictures . As shown in , the main effect for Affect was moderated by a Group × Affect interaction . Post hoc comparisons indicated that the PD patients rated the unpleasant/aversive pictures as less arousing than the controls . The two groups did not differ in their arousal ratings of neutral or pleasant pictures .
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What Are The Signs Of Depression
Depression can sometimes make your Parkinson’s symptoms worse. Get in touch with your doctor if you notice any of these things happening to you for longer than 2 weeks at a time.
- You have a depressed mood.
- You can’t find pleasure in things that you once enjoyed.
- You have trouble getting to sleep or you sleep too much.
- Your appetite changes.
- You have thoughts of death.
Parkinson’s Disease: The Basics
What is Parkinson’s disease? Parkinson’s disease is a neurologic condition that results when dopamine-producing cells in the substantia nigra, located at the top of the brainstem, stop producing sufficient levels of dopamine, which is essential for normal movements.
Why does the loss of these cells cause so many symptoms? Dopamine neurons account for less than 1 percent of the neurons in the brain. The largest cluster, located at the top of the brainstem, has been estimated to number no more than 400,000. However, individual dopamine neurons have as many as 500,000 connections with other neurons, endowing them with enormous influence over our movements, our motivations, and even our emotions.
How common is PD? PD affects about 1 percent of people older than 60 years of age. It affects more men than women. In early-onset PD, symptoms appear between the age of 50. Some reports suggest that 10 percent of all PD cases are early-onset.
What are the symptoms? PD causes trembling in the hands, arms, legs, jaw, and face, along with rigidity of muscles in the arms, legs, and trunk. People with PD also move slowly and sometimes “freeze” entirely for a few seconds. They also have trouble with their balance and coordination.
How is PD diagnosed? Currently there are no laboratory tests to detect PD in the earliest stages. Once motor problems begin, the diagnosis is based primarily on an exam by a neurologist, although brain scans and other tests may be ordered to support the diagnosis.
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Other Mental Health Problems Linked To Parkinson’s
Some mental health issues are side effects of Parkinson’s treatments, like hallucinations, paranoia, and delusions.
A hallucination happens when you think something is present when it isn’t. For example, you may hear a voice but no one is there. An example of paranoia is when you think someone is following you when they are not. A delusion is when you are convinced something is true, despite clear evidence that proves it’s not.
Limitations Of The Existing Animal Models Of Pd
Finally, we have summarized in Table 3 the current knowledge regarding the potential involvement of the neurotransmission systems in the pathophysiology of neuropsychiatric disorders through the different species used . It comes out that, although the DA and 5-HT systems seem to be involved in the pathophysiology of all these symptoms, the other systems have been much less studied. For example, in PD patients, there is evidence for an involvement of the cholinergic system in depression, apathy and psychosis but, to our knowledge, no animal study has yet shown causal links between an alteration of this system and the expression of a neuropsychiatric-like symptom. Furthermore, there is a real need for new preclinical studies on the pathophysiological substrates of apathy, psychosis and ICD as the arsenal of drugs to treat these disorders in patients is limited or non-existent .
Table 3. Overview on the involvement of DA and non-DA systems in the pathophysiology of neuropsychiatric disorders through the different species used.
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Psychiatric Manifestations Of Parkinsons Disease
Parkinsons disease is a common neurodegenerative disorder with an increasing prevalence reflecting the ageing population. Therefore, it is expected that non-motor symptoms, particularly the psychiatric manifestations of PD will become more of a noticeable burden.
More than 60% of patients with Parkinson’s disease report having one or more psychiatric symptom.1 Such complaints may arise from the same pathology underlying the PD, including depression, anxiety, apathy and cognitive impairment, which may worsen as the disease progresses. Dementia is a well recognised complication of PD with a reported prevalence varying from 10-40% in patients with PD.2
Other psychiatric aspects relate more to the treatment of PD and may present as sleep disturbances with vivid dreams and/or nightmares, visual hallucinations, delusions, mania and confusion.
These presentations may in fact occur independently of anti-parkinsonian treatment but are extremely rare and it is only with the introduction of dopaminergic replacement therapy when these symptoms surface. An increasingly recognised complication of anti-parkinsonian medications is dopamine dysregulation syndrome , in which compulsive medication misuse leads to disabling motor and behavioural features.
General management of treatment-related psychosis is difficult, necessitating the need for a reduction of dopaminergic drugs, sometimes at the expense of worsening motor symptoms, and often with the addition of an atypical antipsychotic.
Mutation Affecting Myelin Protein May Raise Parkinsons Risk
Now, seven years after my Parkinsons diagnosis, my ugly days have started increasing in intensity and frequency. Granted, Ive been through a lot in the last couple of years. Im not alone in dealing with a pandemic and social isolation. We have also relocated to a new environment. Moving is always stressful, but it has already increased our quality of life, as long as I can survive all the transitions and challenges of a progressive illness. I cant increase the levodopa due to side effects. My choice is to either give up meaning, live with the results of these threshold-crossing events or design a new brain rehabilitation program for myself.
I describe the basic elements of this program in my new book, Possibilities with Parkinsons: A Fresh Look, and I continue to expand on these ideas in my columns. Ive identified my own episodic symptoms as a flicker effect and use threshold management to monitor and adjust when symptoms start to escalate. Im changing my actions to decrease the flicker effect and the impact of ugly days. The daily application of both threshold management and mindful movements has made a big difference.
Still, life isnt easy. I still get a monkey wrench thrown into my healing routine. Recently, extreme emotions roared back because a broken water heater forced cold showers on me for more than a week, but the experience reaffirmed that I could minimize the impact of disruptions. It was possible.
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Role Of Serotonin In Parkinsons Disease
Studies have shown that the 5-HT transmission system also undergoes degeneration in PD . The neuronal degeneration in the midbrain raphe nuclei is known to lead to reductions in 5-HT and 5-HT transporter levels in brain areas such as the striatum and prefrontal cortex . However, 5-HT neurons have the ability to store and release DA synthesized from systematically administered DA medication such as levodopa . For instance, in a 6-OHDA lesioned rat model of PD with severe nigrostriatal dopaminergic neuron degeneration, it has been shown that striatal reuptake of levodopa-derived DA can occur through 5-HT transporters . Further, it has been shown that monoamine transporter inhibitors such as selective serotonin reuptake inhibitors can modify striatal dopamine reuptake and metabolism so as to improve motor symptoms of PD . A new treatment approach for PD may therefore consist of blocking 5-HT transporters to enhance and/or prolong the antiparkinsonian effects of drugs that have the potential to increase extracellular DA in the striatum including SSRIs.
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.
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Environmental Factors And Exposures
Exposure to pesticides and a history of head injury have each been linked with PD, but the risks are modest. Never drinking caffeinated beverages is also associated with small increases in risk of developing PD.
Low concentrations of urate in the blood is associated with an increased risk of PD.
Drug-induced parkinsonism
Different medical drugs have been implicated in cases of parkinsonism. Drug-induced parkinsonism is normally reversible by stopping the offending agent. Drugs include:
Mimicking Human Conditions In Animal Models
With the advance of the medical research, it is possible to mimic certain human conditions in selected animals, such as mouse or rat, to study the development of a disease and search for treatment. In addition to being very close to the human physiology, these animal models are reliable and critical to develop new treatment strategy and to understand the pathophysiology of a disease.
In the laboratory of Professor Musa V. Mabandla, we have by exposing pups to early maternal separation once daily, from post-natal day 1 to 14. We thereafter injected these rat models with depressive-like behaviors with a preclinical dose of 6-hydroxydopamine stereotaxically into the medial forebrain bundle to mimic Parkinsonism. This has resulted to a rat model of PD associated with depressive-like behaviors.
We also injected these animal models with Fluvoxamine maleate , an antidepressant widely used for the treatment of psychiatric disorders, to investigate the neuroprotective effects of the drug on a parkinsonian rat model of neurodegeneration.
Our findings show that early maternal separation exacerbated the effects of 6-hydroxydopamine, but FM treatment attenuated neurodegeneration associated with 6-hydroxydopamine toxicity.
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How To Cope With Parkinsons Disease At Home
You may wish to make practical arrangements to help you feel more in control of your disease. Here are some tips for coping with Parkinson’s disease at home.
- Improve your sleep health: Make sure your bedroom is set up for sleep. Remove technology devices and other stimulants and try to make your bed a calm sanctuary where you can get the rest you need.
- Keep a medication chart: You may have to take several different medications at a time, so keeping a chart will help you stay organized.
- Ask for help: Find someone you can call on for help when you need it, such as a friendly neighbor, family member or friend.
- Remove hazards: As your Parkinson’s progresses, you may find it difficult to move around freely. You may also experience frozen or shuffling gait, which can catch you off-guard. Make sure to remove trip hazards and fall risks from the home to minimize the chance of injury and ease your anxiety.
As difficult as it may seem, many people find ways to live successful and happy lives with Parkinson’s disease. It may take a while to find the right medication to control your symptoms, and it might not be the whole answer. However, there will be a route through this, and you can find new ways to make your life enjoyable and meaningful
Coping With The Diagnosis
In the midst of the medical treatment of Parkinsons, it may be useful to consider how psychological and emotional processing is affecting your overall coping.
For some, the emotional adjustment to Parkinsons can be as difficult as coping with the physical symptoms. It can include coping with ones body changing along with the need for new personality characteristics, such as increased dependence on others.
For caregivers, there can be a different adjustment. Caregiving often occurs in private. Attempting to minimize the impact of providing daily support along with the personal cost of caregiving can lead to the experience of ongoing sadness, grief, and sorrow.2
People with Parkinsons may also experience chronic sorrow related to disrupted plans, the need to ask for help and depend more on others, as well as limited socialization and challenges related to participating in former hobbies.1
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Discuss With Your Physician
Non-motor symptoms can sometimes be difficult to recognize. Therefore, it is important to make your doctor aware of them.
One useful resource is the PD NMS Questionnaire. You can use this to record your symptoms and discuss them with your doctor.
Dr. Ron Postuma, whose research was funded by donations to the Parkinson Canada Research Program, has also developed tools to help people with Parkinsons and their physicians identify and manage non-motor symptoms.
Stooping Or Hunching Over
Are you not standing up as straight as you used to? If you or your family or friends notice that you seem to be stooping, leaning or slouching when you stand, it could be a sign of Parkinson’s disease .
What is normal?If you have pain from an injury or if you are sick, it might cause you to stand crookedly. Also, a problem with your bones can make you hunch over.
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Emotional Aspects Of Parkinsons
It is important to examine the various emotions that a person living with Parkinsons disease can undergo in living daily with the condition. The emotional factors that affect your loved one can be both internal and external. Some changes that occur can be directly due to the disease process, which causes an alteration in brain chemistry. Other emotional changes are influenced by external factors and the persons reaction to those factors.
Having a chronic neurological condition is stressful, and people react to stress in different ways. Some see it as a challenge and others see it as a problem. Parkinsons disease has a significant impact on family and friends and can create many emotions. These emotions include:
DENIAL/DISBELIEF
Denial, a feeling of shock and disbelief is a common reaction, especially at the time of initial diagnosis and early in the disease process. Since PD can have a subtle onset before an actual diagnosis is made, people often attribute symptoms to other causes. People also sometimes report a general feeling of uneasiness or an anxious, depressed feeling prior to diagnosis. When a diagnosis is finally made, it can come partially as a relief, but there is often shock and fear of the future.
DEPRESSION
Depression is one of the most common reactions to Parkinsons disease, occurring in roughly 50 percent of clients. Some doctors feel that depression may actually be part of the disease process. PD medications can also cause depression in some patients.