Stress
 

We all know that stress is the Enemy, ready to rob us of our ability to function.

We also know that it is common for PD to come along after a stressful trigger such as the flu or tragedies.

We also learned in a lengthy thread on the old BT2 that, somewhat to our surprise, the great majority of us had a lot of stress in our lives growing up. I had an alcoholic father. Ron had the Blitz. Most of us fell in between but "high-stress" was typical for our childhoods and/or youth.

Now I would like to extend this a little and ask you all this question:

Based on what you know of your parent's early lives together, would you rate your mother's exposure to stress while she carried you as low, medium, or high?

Was she a worrier? Did she have the flu? Was your dad out of work? What was life like for her during those nine critical months? It may be important.

My father was manic depressive. I was born in 1948, within a year of his return from Europe and WWII. Between those two and my mother's controlling father, I would say my mother's life was stressful.

Have you found some research about this possible link? Or are you speculating, as any good researcher would do :)

From what I know, my mother was probably under an awful lot of stress when she was pregnant with me.

I'd like a few more replies before I get in very deep...
 

...but I've been reading and thinking, a dangerous combination :)

One thing I have been thinking about is the original descriptionof PD in Parkinson's infamous essay of 1817. Given how "noticeable" our condition is and how prevalent, why was it not described sooner?

The traditional speculation has been that the advent of the Industrial Revolution brought new toxins into the picture and that that triggered it, but I wonder.

Another thing that the IR brought was massive, rapid, and sustained change in society. A society can adapt adapt massive and rapid, but sustained (continuing) poses a different problem because adaptation is constant and there is no time for the systems to rest.

The reason I wondered about yo' mama is that stress on her affected the way we developed. And there is research that indicates that the effect can reverberate down several generations.

Then the question becomes what stresses were our grandmothers under and how are they affecting us today. And an even bigger one, do the effects accumulate and get more pronounced with each generation.

Sure are a lot of younger Parkies around then I would have expected....:confused:

Now there is an interesting statement! And interesting probably isn't a strong enough word to use.

I believe one would be hard pressed to find a human being on planet earth who isn't stressed today...finances, doing more with less at work, hunger (e.g. Darfur), living in cars/street, two income family, too much stuff (e.g. ipod, cell phone), climate change, discord between religions, fear of lawsuit, increase in the incidence of disease, living paycheck to paycheck, increase in # of socialist countries...heck, just the fear of allowing children to stand at a bus stop alone...goes on and on.

Suffice it to say, if there is a correlation between stress during pregnancy...well, that is pretty scary just in thought.

While I clearly believe that the toxins we breath and eat in our food are the two primary reasons for the increase in the incidence of disease, to add stress during pregnancy, which is relatively unavoidable, and that effect on children. I am :Speechless:

Nothing is ever that simple with PD
 

When an embryo is forming, there are critical "windows" of time when particular parts are being formed and the nervous system is no exception. These windows may be only hours in length and may occur once today and then again for further genesis next week and so on. During those few hours the embryo is very vunerable to "outside" factors interfering with its formation. One of the vulnerabilities is the establishment of neurochemical relationships between hormones and receptors. The embryonic receptor is "locked in" by its first encounter with its intended chemical.

The danger is that if similar but different molecules are in the system that a certain number of them will get there first and things will get screwed up. Cortisol and other stress-related chemicals from the maternal system are one of the possible "spoilers". If mama is stressed during just the right time, her baby will bear a lifelong imprint. In fact, this is called "hormonal imprinting".

So, it's not that our mothers are expected to be non-stressed all the time. But if she is stressed ALL the time, then we can expect to be born with certain problems. Depending on the timing and the individual and later factors encountered (nutrition for example) these problems can be diabetes, anxiety disorders, schizophrenia, hypertension, etc.

So, folks, do you think your mother was stressed a lot when she was carrying you? So far three out of three say yes. We need a bigger sample. Who will be number four? :)

Well, I can't say for sure that my mother was stressed when I was developing, but I do know two things: she was subject to anxiety to the point of a nervous breakdown as a young woman, and she had been told before I was conceived that having another baby could kill her. So I'd say she was probably pretty highly stressed.

Stress
 

Hi Rick,
I agree with Carolyn that everyone in modern living is stressed, but there is stress and extreme stress. I was born in 1936, and my parents had just bought their first house, with a heavy mortgage. My father was frequently out of work, and income was spasmodic. I remember my mother telling me that at one time, my father had raging toothache, but had not the money to go to a dentist. His schooling had stopped at 14, and he had given a false age when he was 16, to get into the army and fight in WW1. The storm clouds of WW2 were gathering, and it was clear there was going to be a war. My brother (aged 4 when my mother was carrying me) had a dreadful skin disease, and had to be bathed and covered in fresh bandages every couple of hours.
Times were much harder then, and I feel my mother was under extreme stress at the time she carried me. One thing that argues against this theory in my case, is that my sister was born in Feb.1942, and 9 months earlier, the German blitz fell on where we lived in Liverpool. I remember the bombing vividly, the German bombers were aiming for the vital docks, but with no laser targetting, they tended to saturate whole areas with bombs, (shock and awe!!!) Houses all around us were destroyed, and we waited for it to be us.
So why doesn't my sister suffer from PD? The only thing you can say about that is, she is in her mid 60's, and doesn't suffer YET!! I am 70.
I have raised previously the effect of a stress situation (which is known to open the pores of the blood brain barrier, (BBB) and admit toxins to the brain). I believe this is the cause of the worsening in symptoms in PD in a stress situation. PD people have been shown to have a more porous BBB or "leaky" BBB.

See
http://neurotalk.psychcentral.com/showthread.php?t=190
&highlight=Blood+Brain+Barrier


Presumably, the foetus similarly is given a dose of toxins when the mother suffers extreme stress, so maybe there is something in this idea. There may be a reduction in dopamine neurons, but enough neurons to last a number of decades, before natural loss of neurons with ageing, causes the threshold of 20% left, and PD symptoms start to show.

Ron

Ron...
 

...the timing is the critical thing. We are talking about "windows" sometimes as short as a few hours, so there is a lot of room for variance there.

The picture that is emerging is known as the "multiple hits" hypothesis and it is largely common sense. Assume there are a dozen possible factors that taken by themselves don't trigger problems but the more one encounters the greater the odds of PD or any of several other conditions developing.

The various factors have different levels of danger based on their impact and their prevalence. Stress scores big in both areas but even it doesn't trip the system by itself. But add in something like rotenone or our old friend H pylori and the odds shift.

While the following abstract doesn't address stress per se, it does give a hint at how this might work. And, by the way, this complexity is not necessarily cause for despair. Having multiple factors opens up multiple opportunities for therapies.

1: Exp Neurol. 2004 Dec;190(2):373-83.

Rotenone potentiates dopamine neuron loss in animals exposed to
lipopolysaccharide prenatally.

Ling Z, Chang QA, Tong CW, Leurgans SE, Lipton JW, Carvey PM.

Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612,
USA. zling@rush.edu

We previously demonstrated that treating gravid female rats with the
bacteriotoxin lipopolysaccharide (LPS) led to the birth of offspring with fewer
than normal dopamine (DA) neurons. This DA neuron loss was long-lived and
associated with permanent increases in the pro-inflammatory cytokine tumor
necrosis factor alpha (TNFalpha). Because of this pro-inflammatory state, we
hypothesized that these animals would be more susceptible to subsequent exposure
of DA neurotoxins. We tested this hypothesis by treating female Sprague-Dawley
rats exposed to LPS or saline prenatally with a subtoxic dose of the DA
neurotoxin rotenone (1.25 mg/kg per day) or vehicle for 14 days when they were
16 months old. After another 14 days, the animals were sacrificed. Tyrosine
hydroxylase-immunoreactive (THir) cell counts were used as an index of DA neuron
survival. Animals exposed to LPS prenatally or rotenone postnatally exhibited a
22% and 3%, respectively, decrease in THir cell counts relative to controls. The
combined effects of prenatal LPS and postnatal rotenone exposure produced a
synergistic 39% THir cell loss relative to controls. This loss was associated
with decreased striatal DA and increased striatal DA activity ([HVA]/[DA]) and
TNFalpha. Animals exposed to LPS prenatally exhibited a marked increase in the
number of reactive microglia that was further increased by rotenone exposure.
Prenatal LPS exposure also led to increased levels of oxidized proteins and the
formation of alpha-Synuclein and eosin positive inclusions resembling Lewy
bodies. These results suggest that exposure to low doses of an environmental
neurotoxin like rotenone can produce synergistic DA neuron losses in animals
with a preexisting pro-inflammatory state. This supports the notion that
Parkinson's disease (PD) may be caused by multiple factors and the result of
"multiple hits" from environmental toxins.

PMID: 15530876 [PubMed - indexed for MEDLINE]

Yes.
 

My mother was under a lot of stress when she was pregnant with me. My father's business partner was doctoring the firm's books, and when he was discovered, he put the blame on my father who was the junior partner. The case went all the way to the Danish 'Highest Court' where my father won the case. But he had been threatened with jail, and he had to start all over with a loan from his father, whom he hated, and had to set up his office in his father's house for the next six years.
Add to that my father's pathological jealousy - he accused my mother of flirting and having secret trysts with everyone from the cheating business partner to clowns in circus performances. His jealousy lost both him and my mother all their friends from childhood and youth.
My brother was born nine years earlier than me, and was a sickly child. He spent months at a time in hospital during childhood. He seemed to rally as an adult, and grew tall and strong looking, but at around the age of 60 he fell ill with a myriad of symptoms: he fainted, he fell, his heart grew weak, he had unstoppable nose bleeds. His diagnosis was undecided, he got weaker and weaker, and died at the age of 64. I don't think the doctors even considered PD as a possibility, but by now I do.
I've suffered from a certain amount of rigidity as long as I can remember, and my balance has always been iffy - I always fell down stairs and stumbled over pebbles, and I could not do many of the things required in school PD, like climb ropes or jump over 'the horse'. I dreamed of being able to control my movements, of moving with ease. It took many years for me to realize that something was wrong with me because rigidity and bad balance had always been the norm for me.
I have no doubt that my mother's stress during pregnancy damaged both my brother's health and mine - and that that same stress killed my mother, from cancer, at the age of 48.

OK...i`m a twin so .....
 

I sure hope this doesn`t mess things up but I am a twin...which sort of adds a different dimension to the stressed mum in pregnancy theory.
However..and THIS may be relevant;
my mum was a worrier...a hard worker,liked things to be done to the best of her ability,managed the home and 6 children [2 sets of twins] on a shoe string,sewed well into the small hours to keep us all beautifully clothed,worked every hour God sent her,looked out for others,very little time for herself.
My father...a humble,but wise and respected man,rarely complained,satisfied with his lot,happy to sit in front of the tv after his shift in the coalmine.
Stayed calm in situations,placid and even tempered...not very adventurous or inventive [ which mum found frustrating at times] but compensated by his rock steady personality.

I`m like my mum...my twin like my father.
I have PD. She does not.
My mum was like her mum ...[who was known as The angel on earth...such was her gentle nature,but still a worrier.
Both my mum and gran had neurological illnesses..my mum PD...my gran not sure what hers was.

My mum and I went through a highly traumatic experience...leastways we both managed this event similarly...and both showed signs of PD within months of each other.She was diagnosed...and died before I was diagnosed.

My twin manages situations differently to me.
My daughter is like me in looks,and manner...also has the same interests.

I am doing my damndest to ensure she tackles life`s events different to me.

I am encouraging her to CHILL over life`s hiccups....that whatever happens...it isn`t the end of the world.

I grew up scared of making errors....LOVED...but I once on the way home from school picked an overhanging flower from someones garden,to give to my mum. I spent days worrying that I had STOLEN this one lousy flower...and was terrified to go by that house again.
And I once bought flowers to say sorry to my mum for something.She threw them in the bin.

My kids know they can make mistakes and put them right.
I`ve made sure of that.
Does this help?

Six of six so far....
 

....please add to this if you can. In particular, if you know that your mum was NOT stressed during your gestation let us know. Surely we aren't going to hit 100%. Packages aren't wrapped that neatly.

Hypothesis
 

This theory can easily be tested by forming the hypothesis: more people who are conceived and carried in war torn areas are subject to PD.Two large samples of people, one conceived and born in say Plymouth, England which was heavily bombed(39-42 )and another Devon town not bombed such as Barnstaple in North Devon could be compared (I made it two DevonTowns in an attempt to control other variables) These two samples could be compared and the hypothesis proved or disproved using the correct mathematical formula.
My husband, who has P.D, was conceived and carried in Islington,London during the war.He spent his first week of life in and out of an Anderson shelter.His mother often recounted that she came straight out of the maternity hospital and straight into a shelter with him His father was responsible for water supply and could not leave.He had to be one of the first on the site of a bombing.A stressful situation for all

I am 39 and was diagnosed with pd in April 2003, but had symptoms for about 2 yrs prior to that. Mom was 28 when she had me, living in Faifax, VA; she already had my older brother and sister, my dad was working. I do know that while things were relatively comfortable, my mom smoked (as she did with all 5 births-she stopped at the age of 56 after her first cancer surgery) and we moved a lot, before and after my birth. My mom STILL worries about how the physical moves affected me, but maybe the stress of the moves affected her even more. She was raised in the D.C. area and her family was pretty poor; she shouldered a lot of responsibility, being the eldest in her family, and helped nurse both her father in law and her own mother until they passed away, then helped care for her aging father...all shortly before my birth. So I'd say she had a considerable amount of stress. She still does.
The funny thing is, my paternal grandmother is the one who had Parkinson's disease. She died from an intestinal blockage at the age of 75, and had been dealing with PD for about 15 yrs by that time.

My mother,
 

was already showing PD symptoms at age 37 when I was concieved in 1937. She passed in 1972 at age 72 of PD complications. She lived with the disease for 35 years, longer than anyone else that I am aware of.

A brother 12 years older than I was diagnosed at age 63, as I was. When he passed in 2003 at age 77 of PD complications, his autopsy showed extensive Lewy body disease. In 2002, following my Dx, we entered PROGENI, a research study on PD families at Indiana University.

A sister 10 years older than I did not exhibit overt PD symptoms, but began having dementia with hallucinations 5 years or so before she passed at 72 from pneumonia and kidney failure. No autopsy was performed as she was not in the PD sibling study. Hindsight tells me that she probably had Lewy Body dementia. Before my dx in 2002, we assumed that mom and my older brother had typical sporadic PD. There was no known PD in Mom's family background, although there could have been "shaking palsy" before Parkinson's was recognized as a specific entity.

A sister 18 months older than I is apparently unaffected at age 70. She and my older brother's two unaffected daughters (late 40s, early 50s) are also participants in the PROGENI project.

All of my siblings and I were concieved between 1925 and 1937 at the time of the Depression. My mother was a hard-working stay at home mom and my father was a public secondary school teacher and administrator. They apparently had a model marriage except for the last 15-18 years of my mom's life when she developed psychosis and dementia. We were poor, but never seriously deprived.

The family lived in central Texas during an extensive oil boom in the period of our nativity. I have wondered about possible exposure to petroleum-based neurotoxins that might have contributed to a pre-existing genetic propensity in the affected siblings in my family. My mom fell ill with encephalitis ("sleeping sickness") at age 18, but apparently fully recovered, so her PD may have been associated with that illness, accompanied by a genetic predisposition.

In my opinion, stress was not a major contributor to our disease.

Robert

Eight of eight...
 

...and Robert's familial cluster which presumably gets a class of its own. This is getting interesting. Wouldn't it be something if a thousand Parkies could sit at their keyboards and compare notes? Wonder what we could learn?

But for now, I'd be tickled with twenty replies. Anyone else?

reverett

add my dad to your yes tally. the high list

my grandmother have severe depression and other mental health issues. from her late 20's until she passed away in her 70's she lived in first mental institutions and then a nursing home.

Steffi
 

This is very interesting.........are you an identical twin or are you fraternal ???
I am very anxious to know this.

Caya

reverett,
Put me down on the non stressed list. Seeing as how my mother passed six years after I was born due to an auto accident, and my dad is now gone, I had to go ask other relatives. As far as they can remember my mom was pretty much stress free (or at least as stress free as a pregnant woman can be).

In some of the replies to this question I find some other interesting questions. Steffi, does your twin have PD also? If not, why not? If enviromental toxins and food additives are to blame. why aren't the other family members affected? They were exposed at the same amount you were. On the question of stress, why did I get PD and my brother who was under a lot more stress didn't? Also, going as far back as I can in my family. No one remembers anyone having Parkinson's or shaking palsy. What could I have been exposed to that would cause PD that they weren't and when?

I'm full of questions but after 200+ years no one can answer them.

GregD

Looking back in history, I think there would be a lot more cases of PD if maternal stress were a large factor. The stresses were always there, and still are in countries where starvation and just survival are a way of life. But the toxins were not always there. I think we have brain damage because of what goes into our bodies. Are your teflon pans scratched but you still use them?

To my knowledge my mother was not stressed during her pregnancy with me. I was the first child, and my parents were anticipating it. But I completely agree with the theory that my mother could have injested something toxic that caused my PD. Looking down on the earth from afar, like some big spiritual alien, we look like the malformed animals of the earth suffering from environmental toxins and changes. We have been struck down by something toxic, which could have started with our ancestors and been genetically passed down.

We are doing it to ourselves, and are pretty helpless to stop it. We don't stop using a toxin until it's too late. Although I am not completely trying to blow your theory, and large amounts of stress do cause chemical changes, I have to think that there is a protective buffer from all but extreme cases of stress, which may be all that you are asking.

I understand that you are talking about a small window. But in the scheme of things, I have to think that nature is stronger than that and that it takes a poison to do the damage that we suffer from in increasing numbers.

Cut off the oxygen supply and you suffer brain damage. Drink alcohol at a certain stage of the pregnancy or do drugs and you can have a fetal alcohol syndrome baby, or cocaine babies, which in the older days was probably the child that 'flunked' grades in school. What a miracle that more of us were not fetal alcohol syndrome babies.

I'm squarely in the toxin believing corner. There is a logical order to things, and we do not follow the instructions we are given.

Boy I am in a mood this morning. Must have been the doughnuts.

:D Paula

The dissident voice
 

People in Ethiopia suffer from famines, dire poverty, high infant mortality, failed births, widespread illness, malnutrition, warfare, and lack of healthcare. All far more stressful than what has so far been described, yet they have the world's LOWEST prevalence of Parkinson's Disease.

The Bulgarian Gypsies have Europe's LOWEST prevalence of Parkinson's Disease, despite being renowned for their high rate of alcoholism, crime rates, malnutrition, poverty, unemployment, and ill health.

The prevalence of Parkinson's Disease :

The dissident voice
 

for Caya
 

Hi there...I am a fraternal twin.There are two sets of twins in my family of 6 children.We are the youngest...48 on Thursday !!!:D
The other set is a boy and a girl...late 50`s and my twin is like the other girl in temperament,myself like the boy.

But I have to add this too;
When I was pregnant with my daughter,I suffered very little stress...had a calm pregnancy and her birth was very straightforward and relaxed.

I reinforce...she is like me.She was a sunny baby,but hardly slept.I walked the boards for hours trying to lull her to sleep but the minute you thought she`d gone,up she popped like a space hopper inflating,with bright eyes and a big smile.
She is still nocturnal,but at 14 years,grouchy with it..lol.

However,when I was carrying my son,I suffered stress to the nth degree...was single,ill,suffered huge trauma,and his birth was highly stressful for both him,and myself.He was blue and needed help.
The weeks following were also loaded with anxiety and external trauma.

My son was the perfect baby,rarely cried,non demanding,slept and fed well.He is still laid back with the most caring nature and even temperament.

I am convinced the answer lies within our personalities to some degree...how we deal withi situations,how much workload we give ourselves,how much time,or little time,we give to just chilling out.When I was at the height of my stressful period,I heard things cracking and snapping in my head and suffered the most horrendous headaches.

I swear,if I was in a litter of piglets I would be the runt.I`ve been in hospital more times than I care to mention for various illnesses.More than the rest of my family put together.But I don`t,or didn`t give much time over to me..too busy. Not good....not a good way to be.
Sorry this is lengthy...thought it would be of some importance.
Steffi

Who eze theez masked duck?
 

Some evidence that we may be missing something-

Now before anybody starts quacking, I intend this only to make us think and I concede that animal models have their problems. However, a lot of us have reported our mothers as stressed and stress has a pronounced effect on PD. Finally, don't assume that PD has a *single* cause.

1: Infant Behav Dev. 2006 Jul;29(3):445-55. Epub 2006 May 30.

Prenatal depression effects on the fetus and newborn: a review.

Field T, Diego M, Hernandez-Reif M.

Touch Research Institutes, University of Miami, School of Medicine, P.O. Box
016820, Miami, Florida, 33101, United States. tfield@med.miami.edu

A review of research on prenatal depression effects on the fetus and newborn
suggests that they experience prenatal, perinatal and postnatal complications.
Fetal activity is elevated, prenatal growth is delayed, and prematurity and low
birthweight occur more often. Newborns of depressed mothers then show a
biochemical/physiological profile that mimics their mothers' prenatal
biochemical/physiological profile including elevated cortisol, lower levels of
dopamine and serotonin, greater relative right frontal EEG activation and lower
vagal tone. Elevated prenatal maternal cortisol is the strongest predictor of
these neonatal outcomes. Moderate pressure massage can alleviate these effects
including reducing prematurity.

PMID: 17138297 [PubMed - in process]


1: Physiol Behav. 1991 Mar;49(3):423-6.

Prenatal stress and emotional response of adult offspring.

Suchecki D, Palermo Neto J.

Departamento de Psicobiologia, Escola Paulista de Medicina, Sao Paulo, Brasil.

Pregnant dams were subjected to REM sleep deprivation during different stages of
pregnancy. Pups were reared by their biological mothers and tested as adults for
susceptibility to PTZ-induced convulsions, and ambulation and defecation in an
open-field arena. Adrenal weights were taken at this time. Those animals whose
mothers had been stressed during the first trimester showed a reduction in
ambulatory behavior measured in the open field, and a reduction in adrenal
weight after open-field exposure. Subjects exposed to prenatal stress (PNS)
during the 2nd trimester showed an increased susceptibility to PTZ-induced
clonic convulsions, and a reduction in adrenal weight after PTZ administration
and open-field exposure. Finally, subjects exposed to PNS during the third
trimester showed a reduction in susceptibility to PTZ compared with 2nd week PNS
pups. The results showed different patterns of prenatal stress-induced
behavioral and physiological changes, depending on the developmental stage in
which the stress was applied.

PMID: 2062917 [PubMed - indexed for MEDLINE]


1: Ann N Y Acad Sci. 2006 Jul;1071:351-78.

Glucocorticoid "programming" and PTSD risk.

Seckl JR, Meaney MJ.

Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research
Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. J.Seckl@ed.ac.uk

Epidemiological data have linked an adverse fetal environment with increased
risks of cardiovascular, metabolic, neuroendocrine, and psychiatric disorders in
adulthood. Prenatal stress and/or glucocorticoid excess might underlie this
link. In animal models, prenatal stress, glucocorticoid exposure or
inhibition/knockout of 11 beta-hydroxysteroid dehydrogenase type 2 (11
beta-HSD-2), the feto-placental barrier to maternal glucocorticoids, reduces
birth weight and causes permanent hypertension, hyperglycemia, increased
hypothalamic-pituitary-adrenal (HPA) axis activity and behavior resembling of
anxiety. In humans, 11 beta-HSD-2 gene mutations cause low birth weight and
placental 11 beta-HSD-2 activity correlates directly with birth weight and
inversely with infant blood pressure. Low birth weight babies have higher plasma
cortisol levels throughout adult life, indicating HPA programming. In human
pregnancy, severe maternal stress affects the offspring HPA axis and associates
with neuropsychiatric disorders. Posttraumatic stress disorder (PTSD) appears to
be a variable in the effects. Intriguingly, some of these effects appear to be
'inherited' into a further generation, itself unexposed to exogenous
glucocorticoids at any point in the lifespan from fertilization, implying
epigenetic marks persist into subsequent generation(s). Overall, the data
suggest that prenatal exposure to excess glucocorticoids programs peripheral and
CNS functions in adult life, predisposing to some pathologies, perhaps
protecting from others, and these may be transmitted perhaps to one or two
subsequent generations.

PMID: 16891583 [PubMed - indexed for MEDLINE]


1: Zh Vyssh Nerv Deiat Im I P Pavlova. 1999 May-Jun;49(3):489-94.

[The behavioral effects of a single adverse exposure in a number of rat
generations: the role of maternal glucocorticoids]
[Article in Russian]

Dygalo NN, Sakharov DG, Kalinina TS, Shishkina GT.

Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian
Branch, Novosibirsk.

The ionizing irradiation of rat fetuses during the last third of intrauterine
development increased blood corticosterone level adulthood and decreased the
open field locomotion of their adult offsprings of the next first nonirradiated
generation. Treatment of the pregnant rats with glucocorticoids also decreased
the offspring locomotion. Irradiation of fetuses in the middle of embryogenesis
decreased blood corticosterone level in adulthood and shortened the open-field
freezing reaction of their adult offsprings of the next first nonirradiated
generation. Adrenalectomy of females before mating decreasing the blood
corticosterone level had a similar effect on freezing duration of their adult
offsprings. Irradiation of the ancestors within the last third of their
intrauterine development had no effect on blood corticosterone level of their
adult offsprings of the first generation and produced no behavioral alterations
in their descendants of the next second nonirradiated generation. Irradiation of
the ancestors in the middle of their embryogenesis decreased the stress-induced
corticosterone response in their adult offsprings of the first generation and
increased rearings and locomotion in their descendants of the next second
nonirradiated generation. The data suggest that a single noxious treatment may
have behavioral effects throughout two consequent generations of rats. Mother's
glucocorticoid hormones may be one of the factors which transmit the effect.

PMID: 10420560 [PubMed - indexed for MEDLINE]


1: J Neurosci Res. 2006 Apr;83(5):787-800.

Astrocyte-neuron vulnerability to prenatal stress in the adult rat brain.

Barros VG, Duhalde-Vega M, Caltana L, Brusco A, Antonelli MC.

Instituto de Quimica y Fisicoquimica Biologicas (UBA-CONICET), Facultad de
Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Chronic activation of the stress response during pregnancy has been shown to be
injurious to the development of the offspring. We have previously demonstrated
that restraint prenatal stress inflicted during the last week of pregnancy in
rats increased dopamine and glutamate receptors in forebrain areas of the adult
offsprings. In this study, the same prenatal insult was employed to assess
morphological changes in astrocytes and in the dendritic arborization in frontal
cortex, striatum, and hippocampus of the adult rat brain. On postnatal day 90,
brains were processed for immunocytochemistry using primary antibodies to glial
fibrillary acidic protein (GFAP; the main cytoskeletal astroglial protein),
S100B protein (an astroglial-derived neurotrophic factor), MAP-2 (a
microtubule-associated protein present almost exclusively in dendrites), and
synaptophysin (Syn; one major integral protein of the synaptic vesicles
membrane). The results show a significant increase in the cell area of
GFAP-immunoreactive (-IR) astrocytes, with high levels of S100B protein and a
significant decrease in the relative area of MAP-2-IR neuronal processes in
prenatally stressed adult rats. The expression of synaptophysin decreased in all
areas studied. These results demonstrate that prenatal stress induces a
long-lasting astroglial reaction and a reduced dendritic arborization, with
synaptic loss in the brain of adult offspring. In addition to the neurochemical
alterations previously reported, these morphological changes might be underlying
the behavioral and learning impairment previously observed in prenatally
stressed rats.

PMID: 16493669 [PubMed - indexed for MEDLINE]


1: Neurochem Res. 2002 Nov;27(11):1525-33.

Long-term effects of prenatal stress on dopamine and glutamate receptors in
adult rat brain.

Berger MA, Barros VG, Sarchi MI, Tarazi FI, Antonelli MC.

Instituto de Quimica y Fisicoquimica Biologicas (UBA-CONICET), Facultad de
Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Prenatal stress greatly influences the ability of an individual to manage
stressful events in adulthood. Such vulnerability may result from abnormalities
in the development and integration of forebrain dopaminergic and glutamatergic
projections during the prenatal period. In this study, we assessed the effects
of prenatal stress on the expression of selective dopamine and glutamate
receptor subtypes in the adult offsprings of rats subjected to repeated
restraint stress during the last week of pregnancy. Dopamine D2-like receptors
increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC),
hippocampal CA1 region and core region of nucleus accumbens (NAc) of prenatally
stressed rats compared to control subjects. Glutamate NMDA receptors increased
in MPC, DFC, hippocampal CA1, medial caudate-putamen, as well as in shell and
core regions of NAc. Group III metabotropic glutamate receptors increased in MPC
and DFC of prenatally stressed rats, but remained unchanged in all other regions
examined. These results indicate that stress suffered during the gestational
period has long lasting effects that extend into the adulthood of prenatally
stressed offsprings. Changes in dopamine and glutamate receptor subtype levels
in different forebrain regions of adult rats suggest that the development and
formation of the corticostriatal and corticolimbic pathways may be permanently
altered as a result of stress suffered prenatally. Maldevelopment of these
pathways may provide a neurobiological substrate for the development of
schizophrenia and other idiopathic psychotic disorders.

PMID: 12512957 [PubMed - indexed for MEDLINE]


1: Dev Psychopathol. 1998 Summer;10(3):427-40.

Prenatal stress alters brain biogenic amine levels in primates.

Schneider ML, Clarke AS, Kraemer GW, Roughton EC, Lubach GR, Rimm-Kaufman S,
Schmidt D, Ebert M.

University of Wisconsin-Madison, USA.

In this study, we assessed behavioral responses to social separation at 8 months
of age and cerebrospinal fluid (CSF) concentrations of biogenic amines and
metabolites at 8 and 18 months of age in 12 rhesus monkeys derived from either
stressed or undisturbed pregnancies. Compared to controls from undisturbed
pregnancies, prenatal stress-derived monkeys had higher concentrations of
3-methoxy-4-hydroxyphenylglycol (MHPG), and 3,4-dihydroxyphenylacetic acid in
CSF than controls. Norepinephrine and MHPG response to stress were both
correlated between 8 and 18 months of age. There were few group differences in
behavior during social separation; however, several behavioral differences
between groups were found when monkeys were reunited with cage mates. Prenatally
stressed monkeys spent more time clinging to their surrogates and exploring
(including eating and drinking), while controls showed more locomotion and
social play with their cage mates. Collectively, our findings suggest that
chronic unpredictable psychological stress during pregnancy has long-lasting
effects on noradrenergic and dopaminergic activity and behavior in the offspring
of gestationally stressed primate mothers.

PMID: 9741675 [PubMed - indexed for MEDLINE]

a couple more
 

1: Med Hypotheses. 2007;68(1):46-60. Epub 2006 Sep 7.

Prenatal influences on brain dopamine and their relevance to the rising
incidence of autism.

Previc FH.

10906 Whispering Wind, San Antonio, TX 78230, USA. fprevic@sbcglobal.net

The incidence of autism has risen 10-fold since the early 1980s, with most of
this rise not explainable by changing diagnostic criteria. The rise in autism is
paradoxical in that autism is considered to be one of the most genetically
determined of the major neurodevelopmental disorders and should accordingly
either be stable or even declining. Because a variety of epigenetic influences,
particularly those occurring during the prenatal period, can override or
masquerade as genetic influences, these should be considered as prime
contributors to the recent increase of autism. Prenatal influences on dopamine
activity are especially well-documented, including the effects of maternal
psychosocial stress, maternal fever, maternal genetic and hormonal status, use
of certain medications, urban birth, and fetal hypoxia. All of these factors
have been implicated in the genesis of autism, which is characterized by a
"hyperdopaminergic" state based on evidence from monkey and human behavioral
studies, pharmacological studies in humans, and a left-hemispheric predominance
of both dopamine and autistic-like symptoms. Chronically high maternal levels of
dopamine caused by the pressures of increasingly urbanized societies and by
changing maternal demographics such as increased workforce participation,
educational achievement level, and age at first birth, may be especially
significant epigenetic contributors to the recent autism rise.

PMID: 16959433 [PubMed - in process]

1: Med Hypotheses. 2001 Feb;56(2):246-9.

Autism and Parkinson's disease.

Woodward G.

Department of Neurology, University of Kansas, Kansas City, Kansas, USA.

The pathogenesis of Parkinson's disease, a neurodegenerative disorder, is
multifaceted, having a variety of genetic and environmental factors. There is
considerable evidence to support the role of toxins, particularly pesticides and
herbicides, in at least some of those affected (presumably, mostly the
genetically vulnerable). The pathogenesis of autism is no less complex, but
little is known about the potential role of toxins for autism, a
neurodevelopmental disorder. The incidence of autism appears to be rising, and
early exposure to synthetic chemicals is one suspect for this rise. Impaired
detoxification of certain chemicals may be common to autism and Parkinson's
disease. Further study of environmental influences for either disorder may lead
to important insights regarding causation for both, and perhaps for other
neurodegenerative and neurodevelopmental disorders as well.

PMID: 11425297 [PubMed - indexed for MEDLINE]

great thread
 

all these stories, so interesting. i'm the third of four kids. my mother grew up poor- her father spent seven years serving canada in ww1 and returned an ampuutee. after a few years he left the family and ended up committing suicide. my mother had scholarships through graduate school and was married while working on her phd. she then became a mother and homemaker and never hadto worry abouut finances after that. she was a very robust and healthy. she wasn't particularly stressd during my development.
i'm 46, dx six months, with symptoms going back at least 2 years previous. i'm the most sensitive of my sblings, emotionally and have suffered depression all my adult life. i also became an alcoholic early on and have been in recovery for 20plus years. i believe certain metabolic pathways in me are challenged and resuulted in my pd. i also have psoriasis.

more data more data