THE BRAIN FROM TOP TO BOTTOM

Depression and Manic Depression

Anxiety Disorders

People's serotonin levels are controlled by their genes, which may explain the higher incidence of depression in certain families. But adults' serotonin levels can also be affected by how well their parents took care of them when they were infants.

Experiments have shown that monkeys reared by monkeys other than their own mothers (which represented a stressful situation for them) had lower levels of a serotonin degradation by-product in their blood. These lower levels persisted throughout their adult lives, even in monkeys that had eventually been returned to their mothers.

It thus seems that being deprived of maternal care at an early age may recalibrate our serotonin to a lower level that persists into our adult lives and may potentially cause various psychological problems, including depression.

SEROTONIN AND OTHER MOLECULES INVOLVED IN DEPRESSION

Serotonin is a chemical messenger in the central nervous system and is involved in many physiological functions, including sleep, aggression, eating, sexual behaviour, and depression.

Serotonin is produced by a particular type of neurons, named accordingly: the serotonergic neurons. The cell bodies of these neurons are grouped in several nuclei in the brainstem. A decline in the activity of these neurons is believed to be associated with various forms of depression, in particular those that lead to suicide.

Serotonin is a molecule composed of 10 carbon atoms (black), 12 hydrogen atoms (white), 2 nitrogen atoms (blue), and 1 oxygen atom (red).

But scientists have been able to measure the decline in serotonin levels in the bloodstreams of depressed people only indirectly. After serotonin is released from the nerve ending of a neuron, it is either reabsorbed by that neuron or broken down into another molecule, known as a serotonin degradation by-product. Thus, the more serotonin there is in someone's brain, the more serotonin degradation by-product there will be in that person's blood. In the blood of depressed people, the levels of this by-product have often been found to be abnormally low, which suggests that their serotonin levels are abnormally low as well.

There are specific receptors for serotonin on neurons in several different parts of the brain. Depending on the type of serotonin receptor, serotonin will either excite or inhibit the activity of the neuron on which this receptor is located. Thus it is the differences in the types of serotonin receptors that explain why the same molecule can have a variety of effects.

Increasing the amount of serotonin in depressed patients does not always improve their mood. Some of them will also need more norepinephrine. Still other patients may require a different kind of medication (for example, a mood stabilizer such as lithium).

And even within a family of similar antidepressant medications, some patients will do better with one than with others. Every case of depression thus seems to represent a unique kind of disturbance in the functioning of the brain, so that several different medications often have to be tried before one is found to be effective.

ANTIDEPRESSANTS

Depression has been linked to imbalances in certain chemical messengers in the body, such as serotonin, norepinephrine, and dopamine. Antidepressants—medications that effectively relieve the symptoms of depression—act directly on these neurotransmitters, which represents strong evidence that these chemical messengers are involved in this disorder.

Starting in the mid-20th century, as scientists began to suspect that there were some biochemical bases for depression, they developed several hypotheses that attributed a key role to neurotransmitters: chemical messengers such as serotonin, norepinephrine, and dopamine. The discovery of antidepressant medications-molecules that could effectively calm the symptoms of depression-lent support to these hypotheses, because these molecules acted specifically on these neurotransmitters.

It should be remembered, however, that the primary purpose of neurotransmitters is to let neurons communicate with one another. Thus these diseases must be regarded as the result of disturbances in the communications between neurons.Such disturbances can occur at any of the steps in the transmission of neurotransmitters across synapses and are also the source of the effects that drugs have on the brain. Some of the street drugs that people take to get high—such as ecstasy—exert their effects through mechanisms similar to those of antidepressants.