Depression is a severe and crippling emotional disorder that afflicts some 10-15% of the population worldwide, according to the World Health Organization. While there are many varieties of the disorder, the principal characteristics of the illness remain the same: a reduced level of self-esteem; lack of energy or interest in daily activities; reduced social functioning and damage to personal relationships; changes in appetite and weight; and gloomy and often suicidal thoughts and actions.

At one time, depression was seen as being solely the result of environmental factors such as upbringing, trauma, and stress. Research in the last few decades, however, has begun to reveal that depression has a strong biological basis that interacts with environmental factors to bring on the condition. While the exact interrelationship of these factors is still not fully understood, the research has led to breakthroughs in the use of medications and other treatments that can help depression sufferers lead productive and satisfying lives.

Understanding the biological basis of depression requires a look at how the normal brain operates. Within the brain, special chemicals called neurotransmitters carry out many important functions as they help transfer messages throughout the brain's nerve cells, called neurons. We each have somewhere between 10-100 billion neurons within our brains. Whenever we do anything, react, feel emotions, or think, our neurons transmit messages in the form of electrical impulses from one cell to another in about 1/5,000 of a second. Because they move so quickly, our brains can react instantaneously to stimuli such as pain.

Neurotransmitters travel from neuron to neuron in an orderly fashion. They are specifically shaped so that after they pass from a neuron into the synapse, they can be received onto certain receptors, on a neighboring neuron. Neurotransmitters can fit a number of different receptors, but receptor sites can only receive specific types of neurotransmitters. Upon landing at the receptor site of neuron, the chemical message of the neurotransmitter may either be changed into an electrical impulse and continue on its way through the next neuron, or it may stop where it is. In either case the neurotransmitter releases from the receptor site and floats back into the synapse. It is then removed from the synapse in one of two ways. The neurotransmitter may be broken down by a chemical called monoamine oxidase, or it may be taken back in by the neuron that originally released it, via a process called reuptake.

Of the 30 or so neurotransmitters that have been identified, researchers have discovered associations between clinical depression and the function of three primary neurotransmitters: serotonin, norepinephrine, and dopamine. These function within the limbic structures and hypothalamus – those sections of the brain that regulate emotions, reactions to stress, sleep, appetite, and sexuality.

It is at this point that the research on the exact mechanisms of depression is incomplete. Scientists have been trying to unlock the secret behind clinical depression by trying to understand the way in which antidepressants work on this process to elevate mood and reduce symptoms. In a way that is not clearly understood, antidepressants seem to affect that way that the neurons in the brain deal with their "used" neurotransmitters. Some (the MAOI, or monoamine oxidase inhibitor category of drugs) seem to work by lowering the amounts of the chemical that breaks down certain neurotransmitters; others (the SSRI or selective serotonin reuptake inhibitors) seem to reduce the amount of serotonin that is taken back into the cells, thus freeing more to help elevate mood. Neither mechanism is fully understood. Also, research continues to increase knowledge and effectiveness of these drugs.

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