(That's sarcasm BTW)


1. Psychosomatics. 2010 Nov;51(6):474-9.

The role of inflammatory cytokines in cognition and other non-motor symptoms of
Parkinson's disease.

Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Bienfait K, Dicke A, Kusnekov A.

Psychiatry & Neurology, Robert Wood Johnson Medical School, D207A, 671 Hoes Lane,
Piscataway, NJ 08854, USA. menza@umdnj.edu

BACKGROUND: Parkinson's disease (PD) affects patients' lives with more than just
physical impairment. Many of the non-motor aspects of PD, such as cognitive
impairment, depression, and sleep disturbances, are common and are associated
with a variety of poor outcomes. However, at present, the pathophysiology and
clinical management of these symptoms are poorly understood. OBJECTIVE: The
authors sought to determine the associations between various illness-associated
cytokines, cortisol, and the non-motor symptoms of PD. METHOD: The authors
examined a panel of cytokines (IL-1β, IL-6, IL-10, TNF-α) and cortisol in a
cohort of 52 PD patients with depression. RESULTS: There were a number of
significant correlations between the non-motor symptoms and TNF-α. Specifically,
the authors found that TNF-α (but not IL-1β, IL-6, IL-10, or cortisol) was
significantly correlated with measures of cognition, depression, and disability.
In regression analyses accounting for all variables, TNF-α was consistently
significant in explaining variance in cognition, depression, sleep, and
disability. CONCLUSION: These data are consistent with a growing body of
literature that implicates inflammatory cytokines in neural and behavioral
processes and further suggests that TNF-α may be involved in the production
and/or maintenance of non-motor symptoms in PD.


PMCID: PMC2987579 [Available on 2011/11/1]
PMID: 21051678 [PubMed - in process]

Funny you mention that. I have been reading up on anxiety and PD...this lead to an article where I had a similar reaction. Turns out, YO people are hit hardest by this diagnosis. It hits hard and all over: loss of income and career due to disability; social stigma,relationship problems, ICD and other drug side effects, dealing with chronic health condition. We are under a tremendous amount of stress just waking up in the morning, let alone every work a day stressors that we cannot control. I then think back to those compensatory measures and am amazed all over again that we function as well as we do before meds.

Any links between anxiety and cytokines? I figured out Rick, that my weird episodic 'paralysis' was basically freezing exacerbated by a panic attack. I just didn't know that; I have for the longest time been anxious but never full blown panic attacks. As it turns out PWP do have a high number of diagnosed anxiety disorders centralizing around social phobia, generalized anxiety disorder, and panic disorder. As you point out here, it is a part of disease process and not secondary to our diagnosis. it is showing up very early on and might considered one of our earliest symptoms. I have a few questions right from the start.

Interesting to me is that beta-blockers worked when I was certain that I was having Thyrotoxic Periodic Paralysis, but because they were blunting my panic or limbic system over-reaction. What is similar between having too much thyroid hormone and a panic attack?

If cytokines are linked to anxiety and panic disorder too, what will this mean in terms of biomarkers and Braak's staging?

Lastly not a question, but just noting again the uncanny parallels between encephalitis lethargica and PD. EL often presents with behavioral or mood changes.

Funny, I was going to start looking into anxiety and stress and ran across this abstract I had run across and much to my surprise....cytokines were involved!

In reading these abstracts, it become apparent how a lot of this might fit into the auto immune hypothesis in PD...it looks like cytokines can activate the HPA axis and plays a part in the cascade process. The unique part I ran across actually tied it all together by looking at exogenous stress.

I'm linking to a couple key abstracts outlining basics and following with the stress connection. Rick, I wonder if this at all correlates to your ideas on the role of stress in the etiology of PD? Anyway, as usual, I am loosely piecing things together...it is the first time that I have seen the psycho social connection being stress with neurology and immune system.

Rick, have you been following this in your blog? Or maybe there is no "there". Anyway, just wanted to share. I am noticing how big a role anxiety has played in my version of PD- it was the first symptom to show and is apparently alive and kicking given that I started having panic attacks recently.

Exp Biol Med (Maywood). 2004 Nov;229(10):996-1006.
Unraveling the molecular details involved in the intimate link between the immune and neuroendocrine systems.


Viral Immunol. 2005;18(1):41-78.
Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection.

Finally, I like how these researchers call our HPA axis our "sixth sense".

Bratisl Lek Listy. 1997 Apr;98(4):187-98.
[Is the immune system our sixth sense? Relation between the immune and neuroendocrine systems].

It is all the same thing and the divisions are artificial lines created by men, not nature. Neurotransmitters, cytokines, and hormones are all messengers and the classification as one or another is far more "fuzzy" than we are led to believe.

Distress triggers inflammation and inflammation provokes a stress response. And hormones and cytokines are both as neuroactive as dopamine or any other we are familiar with.

One of our biggest problems is overcoming this division of professional turf.

If you have not seen it, I have attached a survey that Idid on stress and PWP. The comments at the end are telling. I have over 90 now with no change

Attached Files

A Survey of 39 PWP Re Stress and PD.pdf (147.6 KB, 125 views)

After realizing that I had ALOT of anxiety that no dr would ever take seriously here in florida, it was gratifying to finally hear from cleveland clinic that it was very common for folks with PD to have it. too bad i had to go to ohio to find that out . I had dbs on nov 2 and look foward to hopefully regaining some of who i was before "the bear" got me. During this past month i was thinking back to my childhood. There is no way that I would have not become anxious. I was mostly terrified trying to cope with such dysfunction surrounding me. This is what happened to me. I believe that the unrelenting stress actually did change my brain. it started to almost continually produce those harmful chemicals like cortisol in very large amounts. so i stayed "wired" and vigilant, never having anything the same, two days in a row. As a child, there was nobody to turn to, so i tried to "figure it out". I became stoic, refused to have any feelings, i guess because if i could control myself, then I would not feel the anxiety.
Flash foward 40+ years... Now I work as hard as i can to keep everything in some kind of order. i am so "good" it's sickening. i was a woman who could 'handle it all" haha. What a toll to my poor body. That's where my PD came from. The post above mentioned "panic disorder" interesting that the psychologist in ohio described me as possibly having that. It truly amazes me that my entire life I never knew how anxious I really am and have been. this is not a recent change pre parkinson's, unless it's pre parkinson's by 48 years. thanks for listening. if anyone knows how I can save this somewhere on my computer, please tell me, i am technically challenged.
thankyou for continuing to be there as i ramble on... Be encouraged! FG

this is, for sure, my real "pd personality" i never really identified with the type A theory, since i was always sooooo calm. sure.

(This is from my survey at the 57-response point which is the latest that I have compiled. It is a place where each PWP was able to sum up their own perception of stress over the course of their life. Very unscientific yet very revealing. And keep in mind that the stress response is the ultimate "subjective experience". To be quite honest, this little project became so depressing that I shy away from it. But these voices need to be heard and the common threads identified. These broken warriors are, admittedly, at one end of a spectrum but we all have our place on that sad rainbow. There are some big clues here if they can but be teased out. PD is much more than neurology.)



Life Summary

As a child I had what was called "cyclic vomiting". I had severe headaches and vomiting that would last for several days and I would sleep almost the entire time. This would go in cycles happening about every 6 weeks or so. Then as a teen I had severe migraines that continued into my thirties at which time they subsided somewhat. I have had a lot of stress through my life. My parents fought a lot and divorced when I was young. We were poor and did not have enough food or proper medical care.
An unusually stressful life if seen from outside.
my life has been one calamity after another - my birth mother abandone me while myfather was in europw (wwII) - my father was brutal in temperment - he remaarried and that was less than harmonius-- the home situation was so bad that from 10 - 18 i spent summers away from home - i am a viet nam vet --- two marriages do you get the picture???

Childhood very stressful. Loved school it was my escape from home. Left home at age 18. Find it stressful when I think back on my childhood an realize that my mother must have known what was going on but chose to put blinders on. Never had a close relationship with my mother. I also grew up on well water and assume I must have been to pesticides as my stepfather ran a greenhouse and grew carnations. I had to work in the greenhouse as well. I am assuming that pesticides were used but am not sure.
My first 18 years were normal. I was in the military from age 18 to 38. Working long hours and not getting enough sleep, combined with moving caused above average stress.
my life was full of stress, my father i only knew as being sick, he had severe heart problems and then cancer and then he passed. my oldest brother died young of cancer and my youngest brother died 3 years ago. my mother died 15 years ago. i am the only surviving of our immediate family. i was raped at the age of 18 and have a child of rape, i have a granddaughter now that i love dearly but that was very stressful and now the issues have come up again with her and how to tell her what is going on. financially with pd, i barely make it, that is a main stress, you have to choose between eating and meds and a roof over your head every month, that is a constant stress and worry. i worry about being at a store alone that i will fall or not find my way out or i can't handle paying without fumbling. life is a constant stress especially with pd. thank you for taking the time to do this survey, i hope i was helpful in some way.
high stress life

My entire adult life from age 13 on has been a long string of almost uninterrupted stress. First I went blind but my parents were told it was in my head, there was nothing wrong with my eyes. Once it was diagosed, I went to grad school and eventually got my PhD in Research. I have along the way had 20 major surgeries (eg removed gall bladder, repairs from 4+ tear at birth of daughter who was premature etc etc. My work is very stressful and has been so continuously for 35 years. I am a type A person, well recognized in my field and with mega responsibilities. I know I have to start thinking about a successor for my clinical and research center; but at the same time, the final application to get the disorder I have been researching / treating for 35 years is due early 2010 and so I'm working hard on that. I almost never get home earlier than 8 or 9 and work weekends adn "vacations". I don't get sick but i have all sorts of weird physical abnormalities... and have had major surgeries... glad to send medical CV if you are interested. I suspect that continuous stress-related work over a long period is responsible for loss of dopamine.
nursed father with PD for 12 yrs then his death,lost my husband,followed by nursing my mother and her death

I remember being upset when sent to summer camp for the first time at age 8 -- I did not fare well made to swim in the cold early mornings; my parents left me there to go to mexico. Don't know if that pertains... Obviously stressed by my father's sudden death at age 52 and my mother tried to carry on as if nothing were different! I experienced stress throughout college, taking tests, never feeling I had studied "enough", wanting to do well and have fun. Going to the dentist was always stressful, and the orthodontist, who kept braces on my teeth for 8 years of pain and self-consciousness. Stress in relationships -- as a college student, served a dorm advisor and carried alot of people's worries and woes. These specifics are intended to illustrate my stress level and causes. As I've written here, I realize that stress, like beauty, has to be seen through the eyes of the person. Much of what I have suffered as stress, has been demands of my own making. Sure I have come up with outside events, but I realize, for instance, I chewed my fingernails intensely for most of my life - still do to a somewhat lesser extent. That's the personification of stress, if you ask me. I try to keep my sense of humor in the forefront, to combat stress! Nowadays, my parkinsons is causing stress in ways it never had before, making me move slowly, making me tired when I still want to get so much done... stress begets stress, in other words...
I believe that before I engineered my life to be stress free, I was severely affected by stress. I am certain that being a gay man in a small city, and living in denial about it all, as well as coming through the AIDS Crisis created a great deal of stress and I felt it.
The 20 yrs. before I ws dx with PD wetr stressful with a divorce and my job.


I answered this in the previous statement. I had an excessive amount of stress and never dealt well with change.
I don't wish to go into detail, at the present time, anymore than I already have.
I get frustrated with i have limited mobility because before i had PD I was active. Stress contributes to my lack of mobility. I try to stretch and exercise in some capacity EVERY day and that helps in all areas: physically, spiritually, and mentally.
See websie www.ret7eap.com

I've always said stress increases my PD symptoms, but I was thinking in terms of social anxiety, not life stress.
Since retirement 9 years ago, stress is much lower when compared to the working years as an Electronics Engineer. The major stress source in the first 20 years was the military life time frame during the 18 to 22 yr period. In all cases I acclimated to the tasks.
stress with parents being unsupportive cheating husband raising child alone finding new career I have very high expectations for myself I feel I should perform, physically as well as anyone w/o PD
1. Being emotionally, physically abused by my mother until age 17. 2. Moving from my grandparents farm when I was 8 and then moving away totally from my childhood community when I was 12. 3. The divorce of my parents when I was 16, he was a public figure so it led to much gossip. 4. Married wrong man when I was 18. 5. Husband second shift and slept all day, had to care for 3 kids alone, my kids were my joy. 6. Had a very rocky marriage for 28 years, finally left in fear for my life. 7. Former husband continued to threaten and harass until his death in 2004. All of these things led to great stress, the more tired I was the greater the stress, the greater the stress the worse the symptoms (tremors and stiffness being the worse).Themoststress was keeping all this in and trying to appear to the world that all was right with my life.
I'm about the same except that I deal with stress mroe appropriatly
Disfunctional family, married alcoholic. Although life was difficult after divorce the stress level began to decrease. Now I'm married to a wonderful supportive husband and my stress level is extremely low.
debilitating



when I think about my life, I was really a mess even though I didn't realize it at the time. when I Reflect back on my childhood, and early adult life (before I met my husband of 24 yrs.), I don't know how I made it. I've had all the major stress factors: sexual abuse, verbal abuse, divoce, miscarriages, divorced parents, father died, illness, moved many times, financial stress, death of twin grandchildren, daughter diagnosed with MS, strained relationship with mother and brother due to sexual abuse/ It is only through the grace of God that I have survived and I have to consider myself to be so blessed.
I would say the overall level and effects of stress in my lifetime would be high. I have also been diagnosed with familial tremors at the same time of pd diagnosis. come from a family of nervousness: mother, brothers, sisters.
I have already detailed my stressors in previous comments.
Under age 20 life was less stressful than most other people. A very happy time. At age 28 lost my mother who killed herself at age 48.We were very close and I felt much guilt at this time
I was physically allergic to my Mother until age 4. I was raised by my Aunt(my Mother's sister) We moved every couple of years until 1965. The last move was from a small town to a large city. I dropped out of high school my senior year I joined the Navy My Mother slept around alot. My folks got a divorce after 25 years of marriage My Father married my Mother's sister. The aunt that raised me until I was four. I got married at 19 and was shipped to Vietnam 30 days later and have not seen her since. I served a tour of duty with the Brown River Navy in Vietnam
In my mid-40s, had a very stressful several years as chairman of a major department at a major university during very turbulent period (e.g., arson attempt in building, etc.)
I had a relatively carefree childhood. In my late teens I married and had children. The stress started at that point and continued to get worse through my adult life. In my late 40s I experienced significant workplace changes which increased stress astronomically. It continued through to my early 60s when I quit working.
I didn't do with my life what I wanted. The stress of just getting out of bed everyday isvery hard. I do not meet the expectations of my family every day. I have thrown at me every day that I don't work but I'm actually having to work to just move. No one understands so yes there is daily stress.
athere was almost constant stress in my life--I was extremely shy and thus isolated, It wasn't until late teens and college that I had friends. In addition, as the only Jews in our school, my sister and I were subject to antisemitism in our 7th and 8th grade years. Later when I, who am white, married a black person, my family withdrew from us for some years causing me a great deal of grief. In 1975, both my mother and father, whom we were then reconciled with, died, causing me probably the worst stress of my life.

I live and have lived with constant stress most of my adult life. I have been married twice and raised three children to adulthood by myself. I worked 13 years as a prison guard in a male prison to get my oldest through college. I have always been able to make it through.
Life stress became a real issue just prior to my pd symptoms: 1. divorce 2. single parent/college student 4. began teaching Jr. High 3. daughter became addicted to drugs beginning a 4 years of chaos 4. second marriage 5. depression continues resulting in 5+ suicide attempts over a 7 year period (I believe the depression was a result of the pd) 6. death of both parents within 6 mos. 7. placed on disability 8. moved out of state All of the above stress happened during 1995-2009
Overall stress was probably 1 notch higher than the average for reasonably successsful Amereicans. Because of a birth defect, I did not walk until 3 years of age. People would stare at me and, according to my mother, I would glare back at them. On the flip side, I did not let the missing limb keep me from doing anything (Leg amputated at 4.5 years). I played pick-up basketball, baseball and football throughout childhood. I played on a municipal lacrosse team when I was a Junior in High School. I learned to ski on one leg at the age of 40 - and I'm still skiing at 67. I am noow retired and stress is diminished but not eliminated because I have been cooperating with a national prfoject to bring pre-op amputees in communication with amputee volunteers. The startup is somewhat stressful.
stress has definatley effected my immune system, i got sick more frequently, was not able to handle things as well as i would have liked, had a good deal of stress as a single mother (making all of the life and medical decisions myself as well as everyday life)
yes I believe that stress is a pre PD factor.
I do not like to watch movies with to much suspense. I frighten easily. I have dealt with a lot of saddness in my life. i think I live a pretty stress free life compared to most. I don't work, i have loving children and husband. Lots and lots of friends who willingly help if I need anything. I think the greatest stress in my life was being seperated from my parents to go to school we lived in a very remote village in the philippines as missionaries and my siblings and I went to a dormitory to live and go to school My siblings loved it. I hated it. I cried a lot. When I was in 9th grade they moved to the city and I lived with them from then on.
death of father, diagnosis of cancer,change in career
Marriage dissolved. Placement of abusive son outside the home at age 14. Back to work immediately upon marriage breakup. Moved our home many times over the next few years. Younger daughter became pregnant at age 18. Diagnosis of PD. Diagnosis of Diabetes. Major auto accident; most of a year to recover. Both daughters moved to the NE USA within three months of one another, taking my grandchildren with them. Just tons of crises in my life for many, many years. I have moved my home 24 times since 1968 when I married.
The level of stress and their impact in my life have been high. I have more stressful events in my life than most people do. I associate my Parkinson's with these events. It seems related that I have had more serious problems in my life than those around me and during that time started to develop the symptoms of Parkinson's. Though I thought I was handling it all rather well, it appears to me that it was all more than my body could tolerate not only in intensity but duration.
1. Born in the middle of world war 2 to older parents. 2. My father died when I eas 11 years old. 3. My mother had a nervous break down when I was 14 years old. 4. Moved house and went to three schools in one year when I was 14 years old. 5. Started work at 16 years old.

Thanks for all the information. Was not able to access this website:

See website: www.ret7eap.com

I have had led a stressful life too. Used to kid the people i worked with that my own soap operetta would be titled: "As The Stomach Churns".

Mike

I'm right there with you.

Sorry - I've been a lurker on this and another site, but as I see other YO's out there struggling with the same extreme anxiety that has gripped me for the past 6 mo, I must chime in. My neuro has been very sympathetic. He agrees that PD definitely affects the autonomic nervous system. He keeps an eye on my thyroid, too. He briefly gave me propranolol which really helped but hasn't continued it for fear of depression. Interesting that it also works on hyperthyroid problems, eh?(I'm prepared to beg for some over the next few days!) I've tried Lexapro - worked for a while but no more. Have weaned off that stuff. Mirapex - don't really see helping, but haven't had bad side effects. Am weaning off that, too. Main symptom has been tremor for years, but this new anxiety is really hard to deal with. I've always been a nervous/anxious person and believe this definitely has something to do with the PD. My job has become more and more stressful as well.

I read somewhere that PD is all about being out of balance chemically. Anybody seen an endocronologist?

Sorry I've been a lurker on this and another site, but as I've developed this gripping anxiety and had several panic attacks, I need to chime in with other YO's experiencing the same thing. I am talking heart-pounding, shaking, dying-to-run-screaming-from-the-room attacks. Sometimes brought on by obvious stressors, sometimes very random.

Neuro is sympathetic. Understands that PD affects autonomic system. Also keeps an eye on my thyroid. Not out of normal range, but has increased. I seem to have a lot of symptoms of hyperthyroidism. I had a week's prescription of propranolol and it seemed to help, but neuro thinks it may cause depression. I plan to beg at my next visit. Lexapro worked for a while, but no more.

I read somewhere that PD is a lot of our chemicals out of balance: one goes up, another goes down, yada, yada. Has anybody seen an endocronologist?