(4 of 6)
Freud, of course, was right. Modern research indicates that the tendency to develop schizophrenia is hereditary. While the average child has a 1% chance of being stricken, the child of a schizophrenic parent faces 10 times those odds, and if both parents are affected, the likelihood jumps to 40%. But genes do not tell the whole story. Children of parents with schizophrenia raised by adoptive parents who don't have the illness have a somewhat reduced risk. In addition, if one identical twin has the disorder, the odds are just 50% that the other will. Clearly, environmental factors -- stress and possibly even a viral infection during infancy or gestation -- also may play a role in triggering the disease.
The first useful treatment for schizophrenia was discovered by accident. A French surgeon serving in Vietnam in the 1950s noticed that Thorazine, then administered as a sedative, quieted ravings and hallucinations among soldiers awaiting surgery. That prompted a Paris psychiatrist to try the drug on schizophrenics. Thorazine calmed patients and reduced their symptoms. It was quickly proclaimed a miracle drug. Thorazine and related drugs such as haloperidol, fluphenazine and thiothixene soon eclipsed the brutal treatments previously in vogue: lobotomy, primitive electroshock and artificially induced insulin shock. Over the next two decades, nearly half a million patients were discharged from state hospitals in the U.S. and hundreds of thousands more from hospitals in Europe.
But the drawbacks soon became apparent. In addition to producing severe side effects, the drugs leave patients listless and indifferent. In short, while they alleviate the so-called positive symptoms of schizophrenia -- the voices and the delusions -- they do not touch the negative symptoms of apathy and social withdrawal. Furthermore, they provide this limited sort of recovery for just 40% of patients; 30% have flare-ups of madness and must be periodically hospitalized, while the remaining 30% are considered to be "treatment resistant" and are largely confined to mental institutions.
Thorazine works primarily by blocking dopamine, one of the many biochemical messengers used by the brain. This discovery, made by Dr. Arvid Carlsson of Sweden in 1967, led doctors to believe schizophrenia is caused by an excess of dopamine. That explanation has now been dismissed by many researchers as too simplistic.
Clozapine was developed by the Swiss pharmaceutical giant Sandoz as an alternative that avoids most of Thorazine's side effects. As a major bonus, it at least partly reduces the passivity of schizophrenics as well as their more blatant symptoms. In contrast to the Thorazine family of drugs, clozapine primarily blocks the neurotransmitter serotonin, though it also inhibits dopamine transmission to some degree. The fact that it influences both neurotransmitters may help explain its greater effectiveness. Still, "nobody completely understands why clozapine is a superior drug," says Dr. Luis Ramirez, chief of psychiatry at Cleveland's VA hospitals.