Posts tagged: Depression

Losing It

Losing it.  All of us lose “it” at some point.  The “it” appears to be the control exerted by the prefrontal cortex of the brain.  The prefrontal cortex serves many functions, and one of the most important is the inhibition of impulses.  The most common impulses to inhibit are sexual and aggressive urges; though they are not mutually exclusive.  The research of Amy Arnsten at Yale has shown that acute stress releases chemicals that reduces the influence of the prefrontal cortex over these impulses.  Not only is prefrontal control weakened, but more primitive areas of the brain emerge to pick up the slack.

In response to the stress confronting the brain, the less evolved brainstem releases two primary neurotransmitters called dopamine and norepinephrine.  Dr. Arnsten discovered that these neurotransmitters actually diminish the communication between the prefrontal area and other regions of the brain.  Once the regulatory network is down, the base of the brain sends a chemical message to the adrenal glands adjacent to the kidneys, and the adrenal releases a hormone that influences the brain in turn.  Norepinephrine and the adrenal hormone cortisol promotes emotional areas of the brain to be fearful and prepare for possible danger.

Chronic unrelenting stress may actually reduce connections between nerve cells in the inhibitory prefrontal area.  Conversely, nerve connections in the more primitive emotional areas of the brain may expand.  There is some evidence to suggest that shrinkage of neural connections in the prefrontal cortex may play a role in depression, addiction and anxiety disorders.  The neurotransmitter dopamine has been long implicated in addiction, due to its strong influence on habit forming areas of the brain.  It appears that a relatively brief exposure to stress has little lasting affect on brain structure.  The longer stress is experienced, the greater the chance the more primitive emotional brain areas will dominate one’s behavior.
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This feedback loop of the brain may play a role in post-traumatic stress disorder.  The habit forming areas of the brain allow us to quickly acquire skills and behaviors that ensure success in novel environments; for example, a war zone.  The prefrontal cortex allows us to formulate plans and inhibit fearful impulses that would reduce effective functioning.  Once the threat is removed, the dangers already experienced may overwhelm the prefrontal cortex’s ability to inhibit the emotional excitement.  Over time, the dopamine, cortisol and norepinephrine may weaken the prefrontal control to the point that the fearful impulses are rarely blocked.  The unfortunate person may re-experience highly emotional scenes in an uncontrolled and repetitive fashion.  This person would experience substantial stress in a peaceful environment, since the brain continues to assault them with feelings and images that inspire fear and avoidance.

It is still a mystery why some people manage chronic stress well, and others-not so much.  It is conjectured that some lucky people have an enhanced ability to digest the dopamine and epinephrine excreted during stress. They would possess an innate biological resistance to stress.  On the other hand, psychological research has revealed that people with a long record of mastering challenging situations are better able to tolerate stress.  People who are often defeated and overwhelmed by events are more liable to suffer with chronic stress and depression.  A person’s perception of control is a key element in the subjective experience of stress.  To what degree the subjective sense of control is a product of training or brain chemistry is anyone’s guess.  As with most psychological phenomenon, it is likely that both elements play an important role.  Effective behavioral training increases a sense of personal control; decreasing the excretion of stress chemicals.  Inheriting favorable brain chemistry may reduce the biological strength of the stress response.  Nature and nurture.  Can’t get away from it.

Sixty Minutes of Placebo

Recently, the news magazine 60 Minutes offered a piece on the role of placebos in the treatment of depression.  If held to the usual standards of broadcast journalism, the piece would not be particularly disturbing.  The 60 Minutes news magazine, however, has a strong track record of breaking news stories in an accurate and reliable fashion.  Historically, 60 Minutes held a higher standard for the subject matter examined, and the depth of its reportage.  Lesley Stahl’s piece on placebos was a break in this chain.  It tended to confuse the issue, rather than draw a conclusion from the evidence.  The confusion was not limited to the role of placebos, but the role of antidepressants in general.

Lesley Stahl’s piece made the assertion that antidepressant effectiveness is largely due to the placebo effect.  This is not news.  The fact that drug companies only select those studies that are favorable to their drug, suppressing the unfavorable studies, is also not news.  A number of detailed and accurate books have been published on this exact topic-even a critique by a former director of the American Medical Association.  It may have been news if Mrs. Stahl focused on the consequences of suppressing unfavorable studies.  Instead, Mrs. Stahl attempted to appear impartial by berating the Harvard professor whose research has reinforced the role of the placebo.  It may have been news if Mrs. Stahl found that the professor’s research was flawed.  She cast doubt on his conclusions without ever achieving some conclusion of her own.  She appealed to psychiatrists, paid by drug companies, as experts to evaluate the research of an unbiased academic.  At no time in the piece did Mrs. Stahl refer to the professor by his correct title, though she unfailingly referred to drug company psychiatrists by their professional titles.  The end result was to cast doubt on both placebos and antidepressants.

The first fact to consider is that most competent psychiatrists are just as concerned with side-effects as the intended effect.  A patient who cannot sleep is given a sedating antidepressant over one that is activating.  A patient who sleeps too much and can’t wake in the morning is prescribed an activating antidepressant.  Patients who are overweight are prescribed antidepressants that cause minimal weight gain, while those who have lost their appetite and are losing weight are given antidepressants that increase appetite.  The side-effect of medication is often as important in the treatment of depression as the main intended effect.  The only difference between a medication’s side-effect and main effect is the intention of the humans that formulate the drug.  The human body does not know the difference between side and main effects of medications.  This very important feature of antidepressant medication treatment was never mentioned in Mrs. Stahl’s report.

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The third and last fact to consider is that placebos have been researched for over fifty years.  This is far from being newsworthy.  It is like breaking news on the value of soap and water.  The brain’s response to placebos and antidepressant drugs is nearly identical.  Using brain scans that take snapshots of brain metabolism and activation (PET), researchers have discovered that placebos cause a similar increase in brain activation (glucose uptake) as antidepressant medication.  Placebo treatment is not known to cause an increase in brain neurogensis, but this appears to be an artifact of scant research, rather than from actually being disproved.  Well-controlled studies may yet reveal that placebos cause neurogensis, but there is little economic motivation to perform this study.  If Mrs. Stahl questioned why drug companies decline to research placebos, that may have been newsworthy as well.

In summary, Lesley Stahl danced around the relevant issues regarding antidepressant medications.  Perhaps she was unaware that the side-effects of drugs may be therapeutic, that SSRIs potentiate neurogenesis, and that both placebos and drugs affect glucose metabolism in a similar fashion.  Mrs. Stahl fell short of asking relevant questions; for example, should antidepressant medication be used primarily for its side effect(s), should physicians continue to recommend drug treatment over psychotherapy, and should drug companies market psychotherapy in combination with placebos or antidepressants?  Any one of these questions may have received an answer that could have changed the future of depression treatment.  Important aspects of depression treatment were ignored, while well-proven old information was touted as breaking news.  Lesley Stahl’s piece failed to arrive at a conclusion, let alone a call to action.  It is unfortunate that the net effect of Mrs. Stahl’s piece will be to further confuse the issues surrounding the current treatment of clinical depression.  It was not 60 Minutes‘ finest hour; certainly not their finest fifteen minutes.