Serotonin and Judgement

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Depression can hit at any age. More than the blues, the overall feeling of doom can trigger some people to kill themselves. Researchers now are looking at this behavior from a new angle. Studies show that low levels of the brain chemical serotonin can in part lead to an overall insensitivity to future consequences, setting off impulsive and aggressive behaviors and perhaps culminating in suicide. By selectively restoring the chemicals' activity researchers hope to prevent destructive behavior as well as head off suicide -- the eighth leading cause of death in the U.S.

Grades are posted. Alex . . . 98 percent. Pam ... 85 percent. Nick...91 percent. Your grade? 20 percent. You're upset so you talk to your teacher to find out where you went wrong. But what if your feelings went out of control? You rip up the posted mid-term grades and glare at your teacher as you exit the classroom. In the days that follow you experience overwhelming feelings of sadness and thoughts of ending your life. Why would a person behave one way rather than another? For years, scientists have agreed that some behavior flaws can arise from environmental influences including how your parents raised you or from a traumatic life crisis such as the death of a loved one. Now a growing body of evidence suggests that a chemical dubbed serotonin (ser-oh-TOE-nin) also may play a part. Some scientists believe that low activity of the chemical in the brain can lead to an underlying inability to handle powerful feelings, which can result in impulsive acts, aggressive behaviors and suicidal tendencies.

This new line of research may lead to:

• The use of brain imaging techniques for identifying those who may be impulsively aggressive or suicidal.
• A method to monitor the serotonin medications given to suicidal depressed patients.
• New insights on the mechanisms of serotonin.

Serotonin is one of a group of chemical messengers known as neurotransmitters that carry out communication in the brain and body. The message molecules flow from a nerve cell or neuron onto other neurons that act as receivers. There, they attach to a distinctly shaped area on the neuron called a receptor site. This union, which is like a key fitting into a lock, triggers signals that either allow the message to be passed on to other cells or prevent the message from being forwarded. Since the discovery of serotonin in the 1950s, researchers are finding evidence that one of its roles is to mediate emotions and judgment. For example, in animal studies, scientists discovered that low serotonin levels may be associated with impulsive or risky behavior. Researchers observed monkeys and found that the ones who took more dangerous leaps traveling from tree to tree had lower serotonin levels and more injuries from falling. Other scientists examined rats and found the ones with low serotonin levels chose a small immediate reward instead of waiting for a bigger prize. Scientists also have compiled studies that show serotonin is implicated in aggressive acts. One example involves mice who lack one type of receptor that responds to serotonin. These defective mice attack intruders faster and more intensely. Other researchers examined the spinal fluid of murderers in Finland. Their results indicate that these individuals have abnormally low levels of serotonin. Some researchers now believe that suicide may be the ultimate act of inwardly directed impulsive aggression. In one new area of research, scientists are examining humans with brain imaging techniques and believe defects in serotonin processing are partially responsible for suicidal behavior. Preliminary results show that depressed people who have attempted suicide exhibit lower serotonin activity (see brain images) in response to a drug that boosts the amount of the chemical in the brain. In addition, the depressed had a history of comitting impulsive acts including overeating and aggressive behaviors such as lighting fires or fighting. Scientists plan to uncover the brain areas where serotonin's inactivity causes the most havoc and identify all the components that play a role in the defective processing. Researchers view the brain in action with a special imaging technique called positron emission tomography (pet). These pet scans compare the brain activity of a severely depressed patient (left) to a healthy volunteer (right). Both people received a drug called fenfluramine that is known to increase the availability of serotonin in the brain. The scans demonstrate that only the healthy patient has an increase in serotonin activity, which is represented by the orange and yellow shading. This suggests that the severely depressed have a very blunted response to the neurotransmitter or very low serotonin levels. Researchers plan to use the technology to devise imaging guidelines that would identify patients with this deficiency.

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J. John Mann, Columbia Presbyterian Medical Center