Abortion Pill May Help Treat Severe Form of Depression
Erica Goode, New York Times- 10/23/2002

Mifepristone, once called RU-486, is best known as the abortion pill. But some scientists believe that the drug may eventually serve another, far less controversial, purpose: treating a particularly fierce and intractable form of depression. Two small studies, the latest appearing last month in the journal Biological Psychiatry, have found that mifepristone is effective in helping people whose severe depression is accompanied by delusional beliefs or hallucinations. Of the 30 patients in the recent study, those who took mifepristone for seven days at dosages higher than those used for abortions showed substantial and rapid improvement in their symptoms, the researchers found. The drug produced only mild side effects in the study.
   Encouraged by such findings, Corcept Therapeutics, the small California pharmaceutical company that financed the second study, has applied to the Food and Drug Administration for approval to market mifepristone for psychotic depression, and two large clinical trials of the drug are in progress. (Danco Laboratories of New York manufactures and distributes mifepristone, sold as Mifeprex, for ending pregnancy.) Dr. Joseph K Belanoff, a psychiatrist and Corcept's chief executive, said the drug could be available within five years "if everything went well" and mifepristone was found to be safe, as used in the study, and effective for the disorder. Dr. Belanoff was also the lead author of the study published in the journal in September.
   If mifepristone does reach the market, it will be the first medication specifically approved for psychotic depression, which psychiatrists say is the most difficult form of depression to treat. The illness accounts for 15 percent to 19 per-cent of the cases of severe depression diagnosed in the United States, according to a study by Dr. Maurice M. Ohayon and Dr. Alan Schatzberg of the, Stanford medical school to appear soon in The American Journal of Psychiatry. Dr. Schatzberg, Stanford's chairman of psychiatry, is a founder of Concept Therapeutics and a shareholder in the privately held company.
   Patients with psychotic depression often suffer from delusions, believing, for example, that they deserve punishment for imagined crimes or that they have terminal illnesses. Psychiatrists have traditionally treated psychotically depressed patients with some combination of antidepressants, antipsychotic drugs and electroshock therapy, an approach that has yielded only moderate success. But the investigators hope that mifepristone, which patients would take for a short period then return to the usual course of treatment, will relieve symptoms more quickly and effectively.
   A chemical compound used for abortions may seem an odd candidate for a depression drug. But mifepristone attracted the attention of researchers for good reason. Mifepristone induces abortion by blocking the action of progesterone, a hormone necessary for implanting a fertilized egg in the lin-ing of the uterus. But in higher doses, the drug also blocks another hormone, cortisol, which is secreted by the adrenal glands and plays a critical role in the body's response to stress. Patients with psychotic depression, studies have shown, often have elevated lev-els of cortisol.
   Dr. Anthony Rothschild, a professor of psychiatry at the University of Massachu-setts Medical School, who has studied psychotic depression, said he and Dr. Schatzberg had hoped to test RU-486 as a treatment in the late 1980's. "You just couldn't get it because of the political controversy," Dr. Rothschild said. Dr. Dennis Charney, the director of the mood and anxiety disorders research program at the National Institute of Mental Health, said scientists at first assumed that the elevated cortisol levels found in some severely depressed patients were only indirectly related to their illness. In the last few years, however, researchers have demonstrated that stress hormones can have a significant effect on brain areas involved in memory formation, emotion and other mental functions.
   The preliminary studies of mifepristone, said Dr. Charney, an author of a commentary accompanying the recent journal article, suggest that cortisol may be directly connected to the delusions and severe depression that patients experience. Such research, he said,. "suggests that cortisol may be mediating a lot of the symptoms associated with mood disorders." Prednisone, a drug closely related to cortisol, can sometimes produce mood changes and psychosis as side effects, Dr. Charney noted. Still, he said, more research is required before the effectiveness of mifepristone can be confirmed.
   The study published last month, for example, was not double-blinded, a protection that prevents the experimenters from knowing whether a patient is taking the drug being tested or a dummy pill. Dr. Belanoff said the results of the first large double-blinded clinical trial, of 200 patients at 25 medical centers around the country, would be available early next year. A second trial is in the early stages.
   Dr. Belanoff confirmed that one patient in the first clinical trial, a 49-year-old man, had died during the study. But he said an autopsy concluded that the man, who had been taking 11 other medications in addition to mifepristone, died from congestive heart failure, brought on by high blood pressure and heart disease, and that it was unlikely that the death was related to his participation in the clinical trial.
   Even if mifepristone wins approval as a treatment for psychotic depression, the drug's controversial history may make it difficult to dispense, perhaps restricting its use to hospital wards. When, in 2000, the F.D.A. finally approved Mifeprex for abortions, it placed tight restrictions on its use. And the continuing debate over chemical abortion will probably ensure that similar restrictions are applied to mifepristone in any form, even one intended to help the most severely depressed patients.

Patterns Seen in Murderers' Brains
Ned Potter, ABC News- 10/24/2002

Joel Rifkin strangled 17 prostitutes in four years, at random and without remorse. But years after New York police caught him in 1994, he still said he had no idea why he killed. "It was just something that happened and, you know, I had no plans to repeat it," Rifkin said in an interview from prison, where he is serving a life sentence. "Am I just evil? Am I brain-damaged? I mean, these are questions I want answered." So do a lot of scientists. Using imaging techniques that allow them to map the brain with growing precision, they have found subtle but similar patterns in the brain activity of people who commit violent crimes.

The Frontal Lobe
In the 1990s a research team -- led by Adrian Raine of the University of Southern California and Monte Buchsbaum, now at Mount Sinai School of Medicine in New York - did brain scans of 25 convicted murderers. They found that many of the killers had abnormalities in the front sections of the brain -- the so-called frontal lobes. "In the normal person the frontal lobe is one of the most highly active areas of the brain," says Buchsbaum, calling up an image on his computer. He points at a brightly colored cross-section of a man's brain on the screen. "In this individual, who carried out a murder, we can see that the frontal lobe is quite inactive."
   Why does that matter? Because scientists have found that parts of the frontal lobes seem to be involved in planning and organizing, and - perhaps most important to the understanding of violent crime - impulse control. "The frontal lobes are the part of the brain that put a brake on impulses and drives," says Dr. Jonathan Pincus, a psychiatrist at Georgetown University in Washington. "It's the part of the brain that allows us to say, 'Don't do that! Don't say that! It's not appropriate! There are going to be consequences!'" Pincus has examined brain scans of more than 100 killers, including some of Rifkin. He says Rifkin matches many other offenders he's seen: "His frontal lobes were very, very seriously damaged."

Understanding Criminal Urges
That brain deficiency alone is not enough to make a person violent. Researchers say people with poor impulse control may simply seem poorly organized, or socially inept. Researchers cite a myriad of other factors - ranging from schizophrenia to severe abuse in childhood - that may play roles. If a person was badly abused, says Pincus, there may be anger waiting to be released. If the person also has frontal lobe deficiency, he says, "then you have a very dangerous combination of impulses and drives that cannot be easily controlled by the damaged frontal lobes."
   Buchsbaum warns against reading too much into this. Research has moved gradually, partly because doctors do not want to create a false impression that they are looking for ways to excuse violence. Researchers also agree it is far too early to say anything about the serial sniper slayings in Maryland, Virginia and Washington, D.C. "We can't specifically say, 'This person will be a sniper and at age 30 will carry out such-and-such a crime.' That is fundamentally impossible," Buchsbaum says. "What we can do is understand the underlying dimensions of impulse control - how the brain stops behavior - and perhaps we can learn to strengthen this, with educational strategies, or with drugs." Meanwhile, Joel Rifkin concedes that if he were ever set free, he is not sure he could prevent himself from killing again.

Forum on Child Abuse Eyes Role of Age
Patricia Wen, Boston Globe- 10/25/2002

WALTHAM - The tale of Sam Stone and the preschoolers captivated more than 150 Massachusetts judges, lawyers, and therapists at a conference yesterday on the abuse of children. In an experiment described at the conference, 170 preschool children between the ages of 3 and 6 were told about a man named Sam Stone who was clumsy and broke things. Sam Stone soon visited the classroom, walked around barely touching anything, and left. Weeks later, teachers asked the children leading questions about Sam Stone, ''reminding'' them that he had ripped books and damaged teddy bears in the classroom. More than 70 percent of the children between the ages of 3 and 4 agreed that Sam Stone had damaged those things -- some even describing the events in great detail -- while 65 percent of the preschoolers ages 5 and 6 said Sam Stone did nothing of the sort. ''This shows you can create false stories in children,'' said Thomas Lyon, a professor at the University of Southern California Law School.
   The role of age in the validity of a child's testimony, particularly in tense custody disputes that include charges of sexual abuse, was one of the topics at the conference. The two-day meeting, aimed at helping the courts better protect children who are physically or sexually abused, was held at the Massachusetts Medical Society headquarters. Given how traumatic it can be for children to recount these events, speakers emphasized the need to minimize the times children are forced to relive experiences for the benefit of the court.
   One in four to five girls and one in seven to 10 boys is abused before turning 18, according to the Massachusetts Citizens for Children, which sponsored the event that ends today. In 90 percent of the cases, the child knows and trusts the person who commits the abuse.
   Speakers also addressed the need for the court system to better understand the psychological state of mothers upon hearing that their husband has been accused of sexually abusing their child. Rebecca Bolen, a professor at the Boston University School of Social Work, said such charges set up a cascade of events - separation from the husband, loss of income, loss of family structure - that compound the crisis. Too often, she said, these women are perceived as ''hysterical'' when they need more mental health support. Judges talked about the agonizing choices they make each day in sex abuse cases. Juvenile Court Judge Stephen Limon said in the early 1980s, the court system used to believe that ''kids don't lie,'' then in the 1990s, ''people started questioning all kids' testimony.'' ''Now, it's coming back to the middle,'' he said.