Rerun: The Brain is an Ecosystem

Yesterday, I posted a piece challenging the "chemical imbalance" myth, based on Robert Whitaker's account in "Anatomy of an Epidemic." The following, from July last year, logically follows ... 

Moira writes:

"We're being told by experts to quit describing mood disorders as chemical imbalances. What metaphor or analogy shall we deploy to replace chemical imbalance?"

Moira was responding to a piece I posted from a bipolar conference a couple of weeks ago where I had this to report: "We're not talking 'imbalance of chemicals of the brain,' Dr Manji reminded his audience. Instead, think of mood disorders as 'impairments of synaptic and neural plasticity.'"

What this means is that instead of conceptualizing the brain as some sort of uniform chemical soup that could use a bit more serotonin or dopamine, we need to see the brain as a highly intricate ecosystem that requires sophisticated nurture and cultivation. In a guest blog post here, Cristina Romero had this to report from a talk by Kay Jamison:

"The brain is like a pond. It’s like an ecosystem. You want to get the ideal ecosystem and then you don’t want to disturb it very much. ... You want to really create a stable environment."

The brain, like an ecosystem, is highly complex, non-linear, and self-organizing. Both brain scientists and environmentalists describe this self-organizing principle as "homeostasis," where the system maintains its own equilibrium at a particular "set point." Robert Sapolsky in "Why Zebras Don't Get Ulcers" gives the example of perspiration to regulate body temperature.

But what if we're in the desert? If we keep perspiring, we will lose water and die. Here's where "allostasis" kicks in: We stop sweating buckets, our mucus dries up. Once the crisis is over, our body reverts to normal, or - in response to changing circumstances - it may find a new set point.

With "allostatic overload," we are talking system breakdown, such as what may happen with global warming or what is going on right now with the current economic-financial crisis. Allostatic overload is what happens to us when our brains fail to cope. Those of us with mental illness reach overload fairly quickly. When this happens, our brains simply don't reset to normal. We find ourselves caught in a destructive dynamic, trapped in our thoughts and emotions.

Ecosystems operate on "macro" and "micro" levels. This corresponds to the "impairments of synaptic and neural plasticity" that Dr Manji was talking about. Until recent advances in brain imaging and gene technology, we had a vague macro idea of neurotransmitter traffic, which gave rise to the "monoamine hypothesis" to explain mood disorders and other mental illnesses.

A gross oversimplification of this hypothesis resulted in the "chemical imbalance" myth of mental illness, best illustrated in the Zoloft ad below:















Of course, as Dr Sapolsky mentioned in an educational video, the brain is not "undifferentiated tofu." A serotonin or dopamine lube job is is not going to have the same uniform result in different areas of the brain.

Below is a far more sophisticated macro view of the brain:















In the fMRI image, we can view how one particular pathway between two different areas of the brain is supposed to operate when things are going right. When things go wrong, that narrow arrow on the right becomes wide.

The arrows represent neurotransmitter traffic, busy and focused on the left, light and broken up on the right. Too much traffic on the right means the emotional part of the brain is dominating the conversation with the rational part of the brain, which happens a lot of the time to those of us with bipolar.

Think of this macro view as the brain working (or not working) on a "systems level." The "cellular level" represents the micro view. Recall "Nerve A" and "Nerve B" from the Zoloft ad. They were largely empty. Here's an approximation of what is really going on inside the neuron:













When things go wrong inside, the neuron may shrivel and even die. On a macro level, when neurons go off-line and fail to communicate (via neurotransmitters) with other neurons, entire brain systems are compromised. We lose our ability to think and function.

As you can guess, "macro" and "micro" are interconnected. Each regulates the other in highly intricate and virtually infinite ways. When things go right, we can only marvel at this creation of nature. When things go wrong, it's not just a chemical imbalance - it's a catastrophe, a collapse. Think "ecosystem."

Much more in future blog posts ...

Further reading

Check out the Science section to mcmanweb. A sample:

"By learning what happens after dopamine binds to its target neuron, we have been able to behold the brain’s inner watch works and marvel over its elegant complexity. This, in turn, is adding to our understanding of the outer watch works, namely how different parts of the brain talk to each other and how various neurotransmitter systems interact."

RIP Chemical Imbalance in the Brain

As to what causes depression, the short answer is we don't know. It is convenient to say that it is a result of a chemical imbalance in the brain, but this is not entirely accurate ...
- Living Well with Depression and Bipolar Disorder, 2006

Let me rephrase that. "Chemical imbalance in the brain" is wholly inaccurate and misleading. My book goes to great lengths to point out that our brains are not chemical soup, but I was willing to concede it was okay to use the term in a pinch. No more.

Last night, I began reading Robert Whitaker's "Anatomy of an Epidemic," published earlier this year. Robert Whitaker (pictured here) is a journalist who got into reporting on mental health quite by accident. His meticulously researched "Madness in America" (2002) challenged the narrative that the introduction of psychiatric meds changed the treatment of mental illness for the better. His current book continues this line of reasoning.

What jumped out and hit me in the face in reading the first 100 pages is that the "chemical imbalance" myth continues to flourish despite overwhelming evidence to the contrary. Here's how it breaks down:

Psychiatric meds were developed serendipitously, with no knowledge of the underlying brain function. This is old news. The first antidepressants, for instance, were originally developed to treat TB. Some of the patients, it was discovered, became lively. In 1958, inproniazid (an MAO-I) hit the market as a psychic "energizer." A year later, imipramine (a tricyclic) came on the scene.

As Whitaker reports: "The New York Times called them antidepressants for the first time."

The first antipsychotics, in the meantime, came out of research for safe anesthetic agents (and before that for malaria). As part of a cocktail, one experimental med induced "artificial hibernation." In France, in 1952, two doctors used a variation of this med to quiet down psychotic patients. Very soon after, Thorazine (chlorpromazine), came on the market as a major tranquilizer or "neuroleptic" (meaning it took hold of the nervous system).

Whitaker notes: "Physicians in the US similarly understood this drug was not fixing any known pathology." Only in 1963, after an NIMH study, did Thorazine and similar compounds become acknowledged as "antipsychotics". Thus the new psychiatric meds were viewed as antidotes for specific disorders, comparable to antibiotics. But to make their case, scientists needed to backfill their claims with a credible theory.

Employing the equivalent of reverse engineering, researchers figured out that antidepressants worked by enhancing serotonin communication between the neurons. Likewise, antipsychotics took effect by blocking dopamine transmission. So far so good. But, could depression be seen as an undersupply of one neurotransmitter and psychosis an oversupply of another? A "chemical imbalance," in other words?

The obvious way to prove that was to analyze the cerebrospinal fluid (CSF) of unmedicated patients. Serotonin that is not recycled in the brain is metabolized as 5-HIAA. Likewise, dopamine is broken down to HVA. The levels of these metabolites in the CSF are acknowledged to relate to the levels of their corresponding neurotransmitters in the brain. Over the course of fifteen years to the mid-seventies, researchers found that the various metabolite levels in patients were no different than those in the general population.

In other words, no chemical imbalance. This is science at its best, disproving its own claims through its own methods, though the theory kept getting revived from time to time, especially with the commercial success of Prozac.

In the meantime, however, researchers began to paint a far more accurate and nuanced picture. With the administration of an SSRI antidepressant, we have learned, the brain attempts to compensate by turning down serotonin release in presynaptic neurons and reducing the density of serotonin receptors in postsynaptic neurons. This is the brain's attempt to maintain homeostatsis (equilibrium), to keep serotonin at levels as they were prior to the introduction of the drug.

Only after two weeks or more does the antidepressant begin to assert itself. The brain's compensating mechanisms break down. Serotonin now floods the synapse and latches onto postsynaptic receptors. Something similar happens with the introduction of an antipsychotic. Presynaptic neurons react by pumping out more dopamine and postsynaptic neurons increase their density. Only later does the blockade begin.

According to Whitaker, "the medicine clearly doesn't fix a chemical imbalance in the brain." Quite the contrary, these meds are causing chemical imbalances, and science is quite okay with that. Exhibit A cited by Whitaker is a 1996 article by former NIMH director Steve Hyman, which notes that the brain on meds is functioning in a manner that is "qualitatively as well as quantitatively different from the normal state."

In his article, Dr Hyman concludes:

Psychiatric research must now extend its efforts beyond the synapse, to an understanding of cellular and molecular neurobiology (in particular, postreceptor signal transduction) as well as to a better understanding of the architecture and function of neural systems.

It's a new world out there. Forget "chemical imbalance."

For an alternative metaphor, check out The Brain is an Ecosystem.

***

This is the first in a series that intends to use Whitaker's book as a talking point on a vast range of topics. We are not out to prove Whitaker right or wrong. Rather, the purpose is to start a conversation on issues that cry out for our attention. Your comments welcome ...

The Brain is an Ecosystem

Moira writes:

"We're being told by experts to quit describing mood disorders as chemical imbalances. What metaphor or analogy shall we deploy to replace chemical imbalance?"

Moira was responding to a piece I posted from a bipolar conference a couple of weeks ago where I had this to report: "We're not talking 'imbalance of chemicals of the brain,' Dr Manji reminded his audience. Instead, think of mood disorders as 'impairments of synaptic and neural plasticity.'"

What this means is that instead of conceptualizing the brain as some sort of uniform chemical soup that could use a bit more serotonin or dopamine, we need to see the brain as a highly intricate ecosystem that requires sophisticated nurture and cultivation. In a guest blog post here, Cristina Romero had this to report from a talk by Kay Jamison:

"The brain is like a pond. It’s like an ecosystem. You want to get the ideal ecosystem and then you don’t want to disturb it very much. ... You want to really create a stable environment."

The brain, like an ecosystem, is highly complex, non-linear, and self-organizing. Both brain scientists and environmentalists describe this self-organizing principle as "homeostasis," where the system maintains its own equilibrium at a particular "set point." Robert Sapolsky in "Why Zebras Don't Get Ulcers" gives the example of perspiration to regulate body temperature.

But what if we're in the desert? If we keep perspiring, we will lose water and die. Here's where "allostasis" kicks in: We stop sweating buckets, our mucus dries up. Once the crisis is over, our body reverts to normal, or - in response to changing circumstances - it may find a new set point.

With "allostatic overload," we are talking system breakdown, such as what may happen with global warming or what is going on right now with the current economic-financial crisis. Allostatic overload is what happens to us when our brains fail to cope. Those of us with mental illness reach overload fairly quickly. When this happens, our brains simply don't reset to normal. We find ourselves caught in a destructive dynamic, trapped in our thoughts and emotions.

Ecosystems operate on "macro" and "micro" levels. This corresponds to the "impairments of synaptic and neural plasticity" that Dr Manji was talking about. Until recent advances in brain imaging and gene technology, we had a vague macro idea of neurotransmitter traffic, which gave rise to the "monoamine hypothesis" to explain mood disorders and other mental illnesses.

A gross oversimplification of this hypothesis resulted in the "chemical imbalance" myth of mental illness, best illustrated in the Zoloft ad below:















Of course, as Dr Sapolsky mentioned in an educational video, the brain is not "undifferentiated tofu." A serotonin or dopamine lube job is is not going to have the same uniform result in different areas of the brain.

Below is a far more sophisticated macro view of the brain:















In the fMRI image, we can view how one particular pathway between two different areas of the brain is supposed to operate when things are going right. When things go wrong, that narrow arrow on the right becomes wide.

The arrows represent neurotransmitter traffic, busy and focused on the left, light and broken up on the right. Too much traffic on the right means the emotional part of the brain is dominating the conversation with the rational part of the brain, which happens a lot of the time to those of us with bipolar.

Think of this macro view as the brain working (or not working) on a "systems level." The "cellular level" represents the micro view. Recall "Nerve A" and "Nerve B" from the Zoloft ad. They were largely empty. Here's an approximation of what is really going on inside the neuron:













When things go wrong inside, the neuron may shrivel and even die. On a macro level, when neurons go off-line and fail to communicate (via neurotransmitters) with other neurons, entire brain systems are compromised. We lose our ability to think and function.

As you can guess, "macro" and "micro" are interconnected. Each regulates the other in highly intricate and virtually infinite ways. When things go right, we can only marvel at this creation of nature. When things go wrong, it's not just a chemical imbalance - it's a catastrophe, a collapse. Think "ecosystem."

Much more in future blog posts ...

Further reading

Check out the Science section to mcmanweb. A sample:

"By learning what happens after dopamine binds to its target neuron, we have been able to behold the brain’s inner watch works and marvel over its elegant complexity. This, in turn, is adding to our understanding of the outer watch works, namely how different parts of the brain talk to each other and how various neurotransmitter systems interact."