Tuesday, August 17, 2010

Love and Opium

First a few interesting tidbits from the news. The stories reference presentations of data at a conference, so I don't have more specific information. But what there is has some interest from an inflammation/chronic disease perspective:

Childhood stress leads to adult ill health, studies say (BBC)

"A series of studies suggest that childhood stress caused by poverty or abuse can lead to heart disease, inflammation, and speed up cell ageing...In one study, researchers from the University of Pittsburgh looked at the relationship between living in poverty and early signs of heart disease in 200 healthy teenagers. They found that those from the worst-off families had stiffer arteries and higher blood pressure.

Another study presented at the conference showed that childhood events such as the death of a parent or abuse can make people more vulnerable to the effects of stress in later life and even shorten lifespan. Researchers at Ohio State University looked at a group of older adults - some of whom were carers for people with dementia. They measured several markers of inflammation in the blood which can be signs of stress, as well as the length of telomeres - protective caps on the ends of chromosomes which have been linked to age-related diseases.
The 132 participants also answered a questionnaire on depression and past child abuse and neglect. A third study reported some sort of physical, emotional or sexual abuse during childhood. Those who did face adversity as children had shorter telomeres and increased levels of inflammation even after controlling for age, care-giving status, gender, body mass index, exercise and sleep."

I'd like to know how they studied the inflammation, but these studies have another piece of information to add to the big puzzle - psychological stress leading to inflammation leading to chronic disease being a likely scenario.

One more interesting news item from the New York Times - a bunch of neuroscientists go camping to study the effects of turning off all the digital stimuli on the brain. Can neuroscientists just relax in the wild? Either they can't, or they wanted to figure out how to write off the camping trip on their taxes...

But now on to opium! In psychiatry we have a a whole recipe book of diagnoses called the DSM IV-TR. The original DSM was derived from an army handbook used by psychiatrists in WWII, some derived from handbooks developed by the Germans from their observations in the late 19th century, and a lot of the rest derived from psychoanalytic thinking. In the DSM I (1952), there were two kinds of illnesses, for the most part, psychosis and neurosis. Psychotic illnesses were defined by a break from reality (as in paranoid or religious delusions in schizophrenia or manic psychosis), and neurotic illnesses were considered to be reactions to psychological stressors and events.

There is also currently a category of illness that has to do with coping skills and temperament called the "personality disorders." It's not a particularly good term and I wish they had thought of another - "I'm sorry, the diagnosis is that your personality is disordered" is not a particularly useful approach to helping people.

For the longest time, it was thought that psychotic illnesses were more genetic/organic, and neurotic illnesses (such as depressive illness, or post-traumatic stress disorder) were reactions to stress and more amenable to treatment by psychotherapy. A type of personality disorder called "borderline personality disorder" was an exception to the neurotic rule - those afflicted tended to unravel and even appear to be psychotic while receiving the old-fashioned on the couch free association type of therapy called psychoanalysis. That's where the name "borderline" came from in the first place - it was thought to be on the "borderline" between psychosis and neurosis.

What is borderline personality disorder? It describes a type of temperament and coping, usually in women but found in men also, where someone is highly sensitive, prone to dramatic relationships, depression, anxiety, addiction, eating disorders, and self-injurious behavior such as cutting. It is very common, with nearly 6% of the population affected. Unlike depression which tends to come and go over the years, personality disorder symptoms are more stable and chronic, though for most people, borderline symptoms do tend to get better over the decades as we live and learn. It most often develops in someone who was abused as a child, but people can have it without ever being abused. Usually it happens in those cases when there is a mismatch of temperament between parent and child. More modern types of therapy can be helpful for the symptoms, but you can only imagine what it must have been like to have borderline personality disorder and to feel unsure and anxious, free associating on the couch while your therapist said very little back in the psychoanalytic days. That kind of therapy would be like re-experiencing the neglect and abuse of childhood in its own way, and that is why psychoanalysis made borderline personality disorder worse. Ultimately, borderline and some of the other personality disorders can get better as people learn to feel worthy and loved.

But, like everything else, we've discovered that even the personality disorders have biological underpinnings. I'm not sure why people continue to be surprised by these findings - it all happens in our bodies, and is thus mediated by biochemistry. In the case of borderline personality disorder, a paper and editorial in this month's American Journal of Psychiatry explore a link between borderline symptoms and opiate receptors.

We all have opiate receptors. They are activated by our natural endorphins, and can help with pain relief and relaxation. Opiate receptors are also activated by opiates, derived from the opium poppy - morphine, oxycodone, heroin, vicodin, percocet, etc. etc. etc. There are opiate activators found in certain varieties of food, most notably wheat (the exorphins) and milk (beta casein A1). We can increase our own endorphin activity through several behaviors - exercise, binging, binging and purging, and self-injury. (While self-injury is a risk factor for eventual suicide, in general people do not engage in cutting as a suicide attempt, but rather the painful act relieves anxiety and focuses psychic pain on a physical level). The placebo effect is also thought to be mediated through activation of the endorphin system (1).

In the paper, scientists measured how an opiate binder called [11C]carfentanil showed up in the brain of living borderline patients with a history of self-injury and in normal controls. They found pretty significant differences within the two groups, suggesting that the patients with borderline personality disorder who self-injure have differences in their opiate systems. Other studies have shown that people who engage in self-injurious behavior such as cutting have lower levels of endoprhins in the blood at baseline and differences in their endorphin genes compared to non-injurers.

Our endorphins regulate many of our social interactions, and almost anything we do to self-soothe, from childhood on, will activate our endorphin system. A certain subset of people, self-injurers in particular, will have less ability to self-soothe that seems to be genetically mediated, so they may go to more desperate measures (binging, addiction, self-injury) in an attempt to feel better. The same endorphin system deficit can explain some of the social problems that people with borderline personality disorder experience.

There are many levels of speculation to engage in at this point. The deficits run in families, and anyone can see how anxious, addiction-prone families can lead to less than optimal conditions for a growing child trying to find his or her way. Epigenetics may well play a role. Add chronic stress and inflammation, poor health, and SAD - there's a whole recipe for generation after generation of biologically mediated mental distress. Fortunately, as we develop more understanding of the underpinnings of these conditions, we can start helping people with specific and sensible treatments.


  1. Best I can tell, stress causes inflammation and all of the health complications associated with stress (high blood pressure, heart disease, psychological disorders, etc) through the activation of the fight or flight response, which releases cortisol into the blood stream. Cortisol pulls extra glucose into the blood stream, making a high stress lifestyle effectively (drum roll) high carb. In other words, a highly stressful environment is the metabolic equivalent of chasing m&ms all day, the effects of which we learned in depth in Good Calories, Bad Calories.

  2. This new "Development of Agriculture Hypothesis" is posited on exorphins, so it fits the theme of this post.


  3. I've successfully treated night binging on bread with naltrexone, an opiate blocker. Not FDA approved!

  4. Hi Geoff - just musing over your comment. Obesity and cardiac disease and type II diabetes are all correlated with depression. However, overall, the trend in depressed people is to have somewhat lower weight and lower cholesterol (those may be old fashioned numbers. Could be recent increases in atypical depression has changed that, but I don't know). But one could think of stress/high cortisol as metabolic syndrome without the calories, at least at first. I'm going to have to do some more detailed posts on the HPA axis. The "things to look into" list is getting longer. Not the *worst* thing for a blogger - an excess of material to cover!

  5. Hey Emily,

    Looks like this response was at least in part meant for my comment on your cholesterol part 2 post, but I'm going to combine the to discussions because to me they're more similar than different.

    In places with particularly poor nutrition, we tend to see a mixture, the ratio of which varies by age, between people who are particularly skinny or even emaciated, and people who are obese. It's not uncommon to see a 300 lb mother bringing her severely underweight toddler to the emergency room to treat malnutrition. It's not that the mother is hoarding food from her child, both obesity and emaciation are symptoms of malnutrition.

    As such, it is not surprising to me that a diet that lowers cholesterol below normal levels (high fiber, very low fat, sparse in animal products) may result in someone being underweight as well as depressed, not to mention vastly more susceptible to cancer. Long term exposure to that malnutrition will for most people result in obesity eventually, though.

    You've talked at length about how inflammation causes tryptophan to be metabolized into kynurenic and xanthurenic acid rather than as a building block for seratonin. If a high stress environment is causing high cortisol levels which is in turn creating a chronically high blood sugar environment, the insulin damage is undoubtedly a causal agent in the inflammation and thus the depression through the above mechanism.

    Through this mechanism (cortisol -> blood glucose -> insulin response -> inflammation), I can easily see how childhood stress would massively influence brain and body development, resulting in a much higher susceptibility to these agents in the future. I phrased it that way because while there may be some aspects of these developmental problems that cause long term problems down the road, particularly in brain development, I suspect that with the vast majority of them, what you're really dealing with is continued exposure to neolithic agents that results in disease, and it's merely the variability in one's resilience to these agents that determines how long people go without getting sick. Most people can correct most problems with a low carb paleo diet and a little sun exposure.


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