We are in the midst of a revolution in our understanding of how many medicines work. Most students are still taught that the key to their actions is simply a matter of binding to a receptor, and then some magic occurs in the cell. But over the last few years there has been a sea change in how we see the actions of many medicines. In many ways the focus on receptor pharmacology is so 1990s.
Several years ago our group and others began to speculate that one of the ways of modulating the interaction of insulin with cells was to modify the characteristics of the cell membrane in which the insulin receptors sit. If we could change the fluidity of the cell membrane, then we could change the sensitivity of the insulin receptor. We also went a bit further and wondered whether high cholesterol levels might be associated with coronary artery disease because it changed the way in which growth factors interacted with cells in the vessel walls.
One of the reasons that fish oils may yet turn out to be helpful in some mood disorders is because they may change the behavior of cell membranes and therefore the behavior of receptors.
I have admired the work that has bee done by Husseini Manji and his group that is now at the National Institute of Mental Health in Bethesda, Maryland. Their interest is in bipolar disorder and there is a very nice update on the group’s work in the journal Biological Psychiatry.
The group is unraveling the ways in which effective medicines work at the cellular level and what actually goes wrong in bipolar disorder. We know that people with severe mood disorders may experience regional impairments of what we call structural plasticity and cellular resilience. This means that the cells find it more difficult to learn and respond to environmental changes. We think that this is why some people with severe mood problems fail to benefit from many medicines and also have so many long-term cognitive problems. So the search is on for strategies that may enhance and maintain the normal connections between neurons. The good news is that there are several new strategies on the horizon.
This notion of impairment in the normal plasticity and resilience of the brain is also why psychosocial approaches are an essential component of successful treatment. When they are coupled to the right medicine as well as the strategies that we employ in Integrated Medicine, the effects can often be very gratifying.
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