Tuesday, July 28, 2009

Mother Amygdala, Have Mercy Upon Us

Once upon a time I wanted to be a neurosurgeon. But I had this idiotic fear of science class -- it was in the water that they gave to girls in the 1950s. So I headed in another direction. Still I am fascinated by the brain, and will keep sharing the stuff that I learn about it. Today's topic is the amygdala.

Ah, the amygdala, the reptilian brain. It is among the oldest parts of the human brain, regulating memory, emotion and fear. The amygdala associates a strong emotional reaction with a piece of information to imprint that information in your memory. You remember best what you associate with strong emotion. If you walk under a tree in the tropics and a poisonous snake falls on top of you, it is highly beneficial from an evolutionary perspective to remember that tree where those poisonous snakes linger. That's when the amygdala is your friend.

More immediately, when the amygdala fires up, it sends a message to other parts of the brain for immediate action, fight or flight. Which is a good thing when fight or flight are your two best options, and one or the other is needed immediately. It is not so good later on in the evolutionary process, when you need a third option. There are other parts of the brain that are better at the third option. The anterior cingulate cortex handles anticipation of tasks, motivation to solve problems and modulation of emotional response. The prefrontal cortex also deals with emotion, but adds planning, decision making and deliberate action to the amygdala's fight or flight response. In other words, they provide the third option, and fourth and fifth, and take time to consider which one will work best under the current conditions which probably do not include poisonous snakes, except in a metaphorical sense.

As I said last week, the brains of people with depression work differently than the brains of people who have never been depressed, and particularly these parts of the brain. We have the pictures to prove it. Today's bit of research comes from Hooley, Gruber, Parker, Guillaumot, Rogowska, and Yurgelun-Todd, "Cortico-limbic response to personally challenging emotional stimuli after complete recovery from depression," published in Psychiatry Res. 2009 Feb 28:171(2):106-19.

The authors took fMRIs of twenty-three women, twelve of whom had no history of any mental illness and eleven who had completely recovered from depression and had been in remission for an average of twenty months. [I love these fMRI - functional Magnetic Resonance Images - machines. They take pictures inside the brain, lighting up the parts of the brain are that are active. I can think of a million questions that fMRI's can answer. You will find me referring to them a lot.] -- Anyway, while each woman was being scanned, she was listening to a prerecorded message from her own mother. Some of her mother's comments were positive, some were neutral, and some negative. The negative comments were never new; the daughter had heard them before.

The fMRIs of the never-depressed and the recovered-depressed worked the same for positive and neutral comments, i.e., the same parts of the brain were activated and lit up the image. The negative comments, however, were processed totally differently by the two groups. In those who were recovered, the amygdala went to work on their mothers' criticism, while the prefrontal cortex and anterior cingulate cortex were quiet. The opposite for the never depressed, they processed their mothers' criticism in the prefrontal cortex and anterior cingulate cortex, which told the amygdala that it wasn't needed at the moment.

To put it more simply, those who had been depressed were not running their mothers' criticism through the parts of the brain that process thought, make conscious choices and quiet down emotional responses. Instead, the part of the brain that simply reacts to danger did so, unchecked. The "unchecked" part means that stress hormones would be released, bathing the brain with cortisol, which is known to damage and shrink parts of the brain implicated in depression.

Nevertheless, both before and after hearing the comments, both groups reported the same thoughts and feelings. They gave no indication that their processing was different. The experience of the minds did not match the experience of the brains.

Now how is this for weird: I read "Cortico-limbic response" one morning in June. I visited my mother that afternoon. We were talking about this blog and some fund-raising I had done for NAMI. My mother said something about my work in the area of mental illness that threw me for a loop. Later that evening, still hurting from her comment, I reported it to Helen. Helen got very careful in her language, not wanted to set me off further, "I can understand in your context how that might upset you. But I think it could be understood in a different way that another person might find to be neutral."

Well, unlike the women in this study, I am not in remission. So my mind matched my brain, and I knew that I was upset.

Is remission simply the separation of mind and brain, so that the mind feels just fine, even though the brain behaves as problematically as ever? And if so, is this a good thing?

One might argue that if you don't know you are disabled, you will be less so. Our dog Mazie is an example. Everybody feels sorry for our three-legged dog. From her perspective, she simply lives a life in which a lot of people are gentle and sweet to her, while she runs as fast and as gracefully as she ever did pre-amputation. If the person with the depressive brain can get through the day without symptoms, who would want to argue with that?

Except that it keeps coming back. Which makes me wonder if the forms of treatment we currently have, medication and various forms of therapy, merely mask the damage that the brain continues to experience, like how somebody on morphine can keep walking on a sprained ankle. The pain-killer solves the perceived problem in the short run, but at a cost to the body in the long run. Maybe success in the short view is detracting from motivation to address the long view.

I know a little bit about mindfulness, and am hoping to find out more. I wonder if it might address this issue. That day when I was so upset by what my mother said, it was helpful to me to be aware that my amygdala was at it again. Maybe that awareness helped my anterior cingulate cortex to soothe my amygdala, so it could rest. I don't know, because I don't have an fMRI machine handy for these sorts of questions.

Lately I try to track not my thoughts, but my body when I am in pain. I pray for and to my amygdala for healing.

Is there somebody out there who knows if I am on the right track?

Thursday, July 23, 2009

OMG!!! That's What They Said! Relapse

"The goal of treatment was to maximize the number of patients achieving clinical remission because this would then render them eligible for the mood challenge." [italics added]

The winners of this month's Omgodthat'swhattheysaid Award are
Segal, Kennedy, Gemar, Hood, Pedersen, and Buis in "Cognitive Reactivity to Sad Mood Provocation and the Prediction of Depressive Relapse," Archives of General Psychiatry 63:7 July 2006.

They wanted to answer a question I asked in my last post, why does depression come back? Cognitive Behavioral Therapy (CBT) says that automatic negative thoughts cause depression. CBT is designed to make people aware of these thoughts, to interrupt and reframe
them. It is often as effective as antidepressants in treating mild and moderate depression, and better in terms of relapse rate. Nevertheless, people treated with CBT do relapse. One explanation is that CBT addresses the cognitive processes that dominate during a depressive episode, but there are underlying and ingrained thought processes that persist even in remission. Give people a list of adjectives, ask them which apply to them, and those who have been depressed but are in remission will nonetheless pick out more negative words than those who have never been depressed.

The authors theorize that there remains a tendency, even in remission, to revert to a depressive style of processing information under conditions that provoke vulnerability. They hypothesized that the treatment modality, antidepressants or CBT did not matter. What would predict relapse risk would be the level of that residual reactivity.

To overcome methodological limitations of previous studies, this group decided to start with subjects who were currently depressed, then treated to remission by a standard protocol for the study, either
CBT or antidepressants, and then submitted to a mood provocation exercise that would allow the researchers to test their residual reactivity.

Okay, I have problems with an experiment that involves provoking depressive thinking in people who are at risk of relapse. But that is an ethics of design issue. Let's get to this month's Omgodthat'swhattheysaid Award, which is awarded for the use of language.

Under the conditions for the experiment, people who did not achieve remission after two drug trials were eliminated from the study.
And here again is the winning quote: "The goal of treatment was to maximize the number of patients achieving clinical remission because this would then render them eligible for the mood challenge."

Get it? They want to make people feel bad. The goal of treatment for a disease with a 15% mortality rate is to provide subjects, or should we say rather objects for an experiment designed to make them feel bad. That's what they said.

Here is their recipe for creating a bad mood. Listen to Prokofiev's "Russia under the Mongolian Yoke" at a slow speed, while remembering a time in your life when you felt very sad. "This type of provocation (combining elements of music associated with sad mood and autobiographical recall) has been found to be effective in bringing on transient dysphoric mood states." I'll say it's effective. My therapist used to play a particular Enya cd in the waiting room to cover voices in her office. After the fifth time it made me too depressed to talk, she broke it. Of the 127 people who reached remission in this experiment, rather than submit to the mood provocation, fifteen of them evidently thought this experiment was whacked, took their good health and bolted for the door.

I suppose the mood provocation could be justified, ethically speaking, by the fact that these people are bound to experience mood provocation out in the real world anyway, as my experience in my therapist's office demonstrates. In fact, my massage therapist used to play the same cd. But I learned to ask her
to take it off! Part of trying to maintain my health includes avoiding situations that threaten it, which explains why my therapist broke the cd that wasn't even hers, it was her office partner's. While the dysphoric state is said to be transient, if it does indeed cause the subject to revert to depressive thinking, it would reinforce harmful tendencies. The effects of that reinforcement might not be so transient, even after the conscious mood passed. It seems to me, they know their experiment causes harm. They want to find out how much harm.

In any case, the quote for which they won the award reveals their own underlying and ingrained thought processes. The purpose of treatment was not so that sick people would get better. It was so that the researchers could obtain subjects/objects for their experiment.

Following mood provocation both groups, those who were treated with CBT and those treated with antidepressants became about equally sad. They were then tested for cognitive reactivity -- the tendency to think negatively. Those treated with meds became more reactive in their thinking, immediately following the mood provocation. Oddly, the CBT group became less so. The researchers suggest that this might be because the experience triggered their CBT skills.

Eighteen months later, both groups had relatively equal relapse rates, the CBT group slightly less. The greatest indicator of relapse risk was an individual's number of previous episodes, confirming what is well known about MDD. Controlling for medical history, those who had become more reactive following the mood provocation did have a higher relapse rate, regardless of their treatment modality.

One explanation is that there is an underlying
and unconscious cognitive structure in the person in remission, waiting to be activated by a sad mood. Alternately, the cognitive structure could be masked because it is suppressed; the sad mood places an additional load on the effort to suppress it, and eventually too great a load to be maintained. Myself, I would testify that this monitoring of thoughts is exhausting, and I cannot maintain it.

Okay, I will give them this credit, they are investigating what leads to relapse, about which there has not been much research. They are also peeking behind the veil of Cognitive Behavioral Therapy. I like the idea of a nonmedical treatment option for depression, but I do suspect that the "behavioral" part of the therapy is more significant than the "cognitive" part, i.e., that what changes is how the patient reports his/her thoughts, not what is going on inside the skull, that CBT does not go deep enough into the mind to affect the brain. And I note that this research could be cited to demonstrate an issue in my last post, that the mind has feedback loops that tend toward homeostasis, just like the brain. Relapse is all about the mind and the brain both maintaining homeostasis.

If this research leads to an improvement in the therapy, then perhaps that impr
ovement justifies the suffering provoked by the research. Nevertheless I challenge the authors to look at their own underlying thought patterns and cognitive structures in relation to their subjects, as evidenced by their language. What do you think?

And do you have nominations for next months OMGod! Award?

Saturday, July 4, 2009

Mental Health First Aid

We know how to do this.  A car hits a light pole -- somebody, maybe you will call 911.   Somebody is choking in a restaurant -- somebody else, maybe I will leap up to do the Heimlich Maneuver.

It doesn't have to be an emergency. If a friend has a persistent cough, or mentions a bruise that won't go away, or complains about chest pains, we urge them to see a doctor.   We have learned to recognize signs of cancer, heart disease, stroke.  We get involved, we even get on their case when the people we care about need help.

Most of the time we do.  Sometimes we turn away.   Last week I kept having the same two
conversations over and over.  The first was about a man who dangled by a chain from the end of a crane.  He reached out to catch a woman caught in the boil of a dam, to rescue her from drowning.   The second was with friends who just didn't know what to do -- about a cousin who is irrational, a daughter who doesn't get out of bed, a godson who can't keep a job, each of them diagnosable with a serious mental illness, none of them getting treatment.

What To Do When A Friend Has A Mental Illness