Genes linked to depression differ between men and women, according research by George Zubenko of the University of Pittsburgh. His work suggests that there are important differences in the molecular basis of clinical depression in men and women that determine their resistance to stressful events.

?We hope that the tools of reverse genetics will eventually lead to the identification of products of these genes and how they contribute to depression and mood regulation more generally in humans,? Zubenko says.

Zubenko hopes that genetic analysis can be used to help doctors select the best anti-depressant drugs for their patients. ?In current practice, the choice of a particular antidepressant for a patient is largely a hit and miss proposition that often leads to multiple medication trials before the depression lifts. Side effects are common and can be debilitating,? he says.

Zubenko?s team compared genetic markers from 50 men and 50 women with recurrent, early-onset major depressive disorder (RE-MDD) and 50 men and 50 women with no history of the disorder. RE-MDD has a strong hereditary component and affects about three per cent of the general population.

Zubenko thinks work on RE-MDD should also throw light on the causes of MDD. They identified 19 chromosomal regions that were linked to RE-MDD. But only three of these were significantly linked in both men and women. The other 16 were only linked to one sex.

?We suspected there were at least a few different genes involved in making men and women more subject to depression,? Zubenko says. ?The results of this study suggest that sex-specific genes for major recurrent depression may actually be the rule rather than the exception.?

Zubenko hopes the research will help reveal why depression is twice as common in women, but male sufferers are more likely to commit suicide. He says, ?At least one of the regions we found resides on the X chromosome?that might have an obvious impact on the sex ratio.?

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Anxiety disorders may start in infancy, according to Cornelius Gross of Columbia University and his colleagues. They have found that mice that are missing serotonin receptors in the first days of their lives are unusually anxious in adulthood, even if the receptors are later restored.

The neurotransmitter serotonin has long been associated with moods. Mice lacking receptors for serotonin are abnormally anxious, though no one was sure which receptors were responsible.

Gross bred a line of mice that had receptors for the neurotransmitter serotonin only in certain parts of the brain?the hippocampus, the cortex and the amygdala. His group found that even with only these serotonin receptors functioning, the mice behaved normally.

By using genetic engineering, the researchers were able to turn these receptors on and off by administering antibiotics. If they gave the mice doxycycline, the receptors were deactivated. But when they turned them off in adulthood, the animals continued to behave normally.

Then the researchers fed doxycycline to female mice while they were pregnant, so that their babies? receptors were inactive during the embryonic and early postnatal stage. By adulthood the offspring?s receptors were working again.

When tested as adults, these mice showed extreme signs of anxiety and spent much more time hovering around the corners of their cages and huddling inside enclosed spaces, and were too nervous to eat.

?This suggests that in a mouse there?s a time when neurons are actively finding their connections or pruning themselves,? says Gross. Serotonin might have an important role in establishing those connections. During this critical period, the receptors have to be stimulated and a group of events must be set in motion if the animal is to behave normally.

Solomon Snyder, of Johns Hopkins University School of Medicine, thinks this finding might help explain the impact of maternal neglect. He says, ?Perhaps variations in serotonin-sensitive neurons and serotonin receptors in early life account for the importance of maternal nurturing in preventing emotional disturbance in adults.?

To find out how one psychiatrist learned that the government might be creating multiple personalities in people, read ?Bluebird? by Dr. Colin Ross,click here.

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