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One of the biggest risk factors is drugs. People with a genetic predisposition to bipolar disorders live on an unstable emotional fault line. Jar things too much with a lot of recreational chemistry, and the whole foundation can break away, especially when the drugs of choice are cocaine, amphetamines or other stimulants. "We do think that use of stimulating drugs is playing a part in lowering the age of onset," says Hirschfeld.
Stress too can light the bipolar fuse. Many latent emotional disorders, from depression to alcoholism to anxiety conditions, are precipitated by life events such as divorce or death or even a happy rite of passage like starting college. And bipolar disorder can also be set off this way. "Most of us do not think environmental stress causes the disorder," says Dr. Michael Gitlin, head of the mood-disorders clinic at UCLA. "But it can trigger it in people who are already vulnerable."
A decidedly more complicated explanation may be gene penetrance; not every generation of a family susceptible to an illness develops it in the same way. Often, later generations suffer worse than earlier ones because of a genetic mechanism known as trinucleotide repeat expansion. Defective sequences of genes may grow longer each time they are inherited, making it likelier that descendants will come down with the illness. This phenomenon plays a role in Huntington's disease and could be involved in bipolar. "There's a stepwise genetic dose that can increase the risk," theorizes Ketter.
The first part of determining how those genes work is figuring out where they are hiding, and the National Institute of Mental Health is looking hard. Investigators at eight research centers around the country, working under an NIMH grant, are studying the genomes of 500 families with a bipolar history to see what genetic quirks they share. So far, at least 10 of the 46 human chromosomes have shown irregularities that may be linked with the condition. The most interesting is chromosome 22, which has been implicated not only in bipolar disorder but also in schizophrenia and a little-known condition called velo-cardio-facial syndrome, which has schizophrenia links as well. The seeming relatedness of disorders that so prominently feature delusions has not been lost on researchers, though with so much still unknown about chromosome 22--to say nothing of the other nine tentatively linked with bipolar--no one is ready to draw any conclusions. "There are probably genetic variants that cut across multiple systems in the brain," says Dr. John Kelsoe, psychiatric geneticist at the University of California, San Diego.
While this wealth of chromosomal clues makes fascinating work for geneticists, it promises little for bipolar sufferers, at least for the moment. What they want is relief--and fast. Thanks to rapid advances in pharmacology, they are finally getting it. In fact, children on a properly balanced drug regimen supplemented with the right kind of therapy can probably go on to lead normal lives.