Depression

Lesson 8: The Science of Depression

This lesson examines the phenomenon of depression from biological, genetic, and environmental perspectives, and explores new treatments on the horizon.

The Brain

What really goes on in the brain during a depressive episode?

No one actually knows, but the Surgeon General provided us with a fairly useful primer in his Report on Mental Health. The brain, in the words of the Surgeon General, is "the great synthesizer" of the many biological, psychological, and sociocultural phenomena that make us who we are, the product of our genes and experience working together.

The brain is a three-pound mass containing some 100 billion nerve cells - neurons - thousands of different kinds, each forming more than a thousand synaptic connections with other neurons. In all there may be anywhere between 100 trillion and a quadrillion synapses organized into elaborate networks that account for the brain's vast complexity.

Just to give you an idea of how truly complicated the brain is, of 35,000 genes in the human genome, some half to three-quarters of these go into the brain's makeup. So what happens when someone - say a little man inside - decides to throw a switch? To start, signals from the neuron travel out a single extension called the axon that may end in several terminals. These signals are picked up by branches - dendrites - extending from other neurons. Communication occurs at specialized structures called synapses, organized into two parts for sending and receiving. The presynaptic structure is located on a terminal portion of the sending neuron that contains packets of sending chemicals, or neurotransmitters. The postsynaptic structure on the receiving neuron has receptors for these molecules. According to the Report:

"A neurotransmitter can elicit a biological effect in the postsynaptic neuron by binding to a protein called a neurotransmitter receptor. Its job is to pass the information contained in the neurotransmitter message from the synapse to the inside of the receiving cell ... These neurotransmitters are responsible for brain states such as degree of arousal, ability to pay attention, and for putting emotional color or significance on top of cold cognitive information ... It is no wonder that these ... neurotransmitters and their receptors are critical targets of medications used to treat mental disorders."

Dennis Charney MD, who has recently joined the NIMH to head up their new mood and anxiety disorders research program, explained at the national NAMI Conference held in July 2001 in Washington DC that the DSM-IV is based on symptoms rather than biology. The depression you suffer from may have a different physiology entirely than the depression of the person next to you, but the treatments available to us do not recognize this fact of life.

Then Dr Charney said: "Our goal is to get to a diagnostic system based on biology and genes ...We have a plan of how we can get there, a five or 10 year plan." Here's a brief glimpse into the future, according to Dr Charney:

Depression is not just a deficiency of serotonin. In some patients it may be parts of the serotonin system that break down. Prozac and its chemical cousins operate on the serotonin transport site, but there are also 15 or so different serotonin receptors. The serotonin 1A receptor, when not working right, for instance, appears to result in low serotonin in one half of depressed patients in the hippocampus and amygdala (the seat of emotion) of the brain, according to PET imaging done at the NIMH. This work needs to be replicated, Dr Chaney cautions, "but it shows what we can do," and suggests the possibility of developing a "serotonin agonist" to treat the problem.

Here's where it really gets interesting: If SSRIs work by blocking the serotonin transport site, there may be something wrong with the site to begin with. SPEC imaging indicates that one half of depressed patients may be affected this way. According to Dr Chaney, we are learning a lot more about the genetics of this site, and the next step would be to see if the genetic coding of this site corresponds with the imaging. Three studies are in progress.

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