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Stress is to mood what that iceberg was to the Titanic, with therapies increasingly geared toward neutralizing its vast destructive powers. In a 2002 NIMH study, healthy subjects with a certain short variation (allele) to the serotonin transporter gene viewed images of scary faces as their brains were being scanned. The part of the brain which governs fear and arousal - the amygdala - lit up like a Christmas tree.
A year later, a study on a New Zealand population found that those with this very same short allele were far more at risk of depression after being exposed to four or more lifetime stressful events (including employment, finances, housing, health, and relationships) than their long-allele counterparts.
Vulnerability vs Resilience
Is mental illness a "vulnerability" disease? Are the lucky ones, in effect, genetically "resilient" to what life happens to throw their way? Or does life have a way of turning even resilient brains vulnerable?
At the 2002 American Psychiatric Association's annual meeting, Charles Nemeroff MD, PhD of Emory University asked his audience: "Is the biology of depression the biology of early trauma?"
In an experiment designed to startle lab rats by blowing an air puff in their faces, Dr Nemeroff and his colleagues found those who had been separated from their mothers as pups showed a greater stress response, with tissue samples revealing higher concentrations of the hormone CRF (corticotropin-releasing factor).
Women abused in childhood, Dr Nemeroff explained, end up with a sensitized brain system, where CRF receptors are to be found in abundance. Depressed patients have high concentrations of CRF in their cerebrospinal fluid.
A 2000 study that he co-authored with Christine Hein PhD found that women with a history of childhood abuse exhibited increased pituitary and autonomic responses to stress when given math tests and made to speak in public compared with the controls. This was especially true for the women with current depression and anxiety.
The stress response - fight or flight - kept our distant ancestors alert and alive long enough to pass on their genes, which certainly comes in handy in modern life, especially when a zeppelin is chasing you.
As Kurt Vonnegut describes it in his 1973 novel, "Breakfast of Champions":
My mind sent a message to my hypothalamus, told it to release the hormone CRF into the short vessels connecting my hypothalamus and my pituitary gland.
The CRF inspired my pituitary gland to dump the hormone ACTH into my bloodstream. My body had been making and storing ACTH for such an occasion. And nearer and nearer the zeppelin came.
And some of the ACTH in my bloodstream reached the outer shell of my adrenal gland, which had been making and storing glucocorticoids for such emergencies.
My adrenal gland added the glucocorticoids to my bloodstream. They went all over my body, changing glycogen into glucose. Glucose was a muscle food. It would help me fight like a wildcat or run like a deer.
And nearer and nearer the zeppelin came.
My adrenal gland gave me a shot of adrenaline, too. I turned purple as my blood pressure skyrocketed. The adrenaline made my heart go like a burglar alarm. It also stood my hair on end. It also caused coagulants to pour into my bloodstream, so, in case I was wounded, my vital juices wouldn't drain away.
Vonnegut is describing a neuro-endocrine loop known as the hypothalymus-pituitary-adrenal (HPA) axis as it is supposed to act in dangerous situations. But what about when there are no zeppelins in sight, when we simply need to be on our toes? The abused and depressed women in the Heim-Nemeroff study exhibited a six-fold greater ACTH increase over the controls. In effect, these women - who only needed to be sufficiently alert to do math tests and speak in public - were being primed to flee attacking zeppelins.
Throw in an over-reactive amygdala and a picture begins to emerge of the human psyche on the breaking point. As Robert Sapolsky of Stanford describes it in a Sept 2003 article in Scientific American: "When we erroneously believe a stressor is about to happen we have entered the realm of neurosis, anxiety, and paranoia."
All those glucocorticoids Vonnegut was talking about don't simply evaporate. Stress has been linked to just about every physical illness imaginable, whether as a risk factor, a cause, or the triggering event.
In the brain, the neural synapses are flooded, setting the scene for excess glutamate to overstimulate brain cells, leading to neuronal loss and atrophy. In this sense, according to Husseini Manji MD, formerly of the NIMH, mood disorders may be regarded as fundamentally atrophic (ie stemming from brain cells in physical distress) rather than symptomatic.
Back to Freud, of All Things
Of all things, the Freudian-inspired DSM-I of 1952 and the DSM-II of 1968 - the ones that everyone ridicules as pre-modern and unscientific - may have gotten it right. Those early DSMs may have wrongly attributed serious mental illness to neurotic or psychotic-reactions, but they very correctly attributed the stresses of dealing with life as the driving force to these reactions.
The "modern" DSMs III and IV, with their exclusive focus on symptom check-lists, threw us off the scent.
Maybe stress can't account for everything going wrong with our brains, but it always needs to be the first place to look. Modern brain science, in effect, has simply relocated the stress dynamic from the metaphysical construct of the mind to the decidedly more prosaic meat housed inside our skulls.
But not just any old meat. We're talking highly specialized, intricately connected meat - live meat - as sensitive to present and past experience as photosensitive paper is to light. When our environment acts, our brain reacts.
But not blindly. Our stressful reactions are telling us something. That maybe, for instance, we need to get out of our denial and recognize that things at work or in our personal relationships are not okay. That maybe, while we have a chance, we have to change ourselves or change the situation around us. Because, if we don't, our depression or anxiety or mania is going to tell us the same thing, only in a much louder voice, with far fewer choices.
Our environment molds our brains, our brains mold our environment. Round and round it goes, a constant cycle of reaction and adjustment. We the vulnerable tend to have a harder time adapting and adopting, but this very insight also tends to be our best motivator.
Be hopeful, take the initiative, live well ...
Full stress article on mcmanweb