Several years ago, a research group from the United Kingdom announced in the prestigious scientific journal Nature that a gene for schizophrenia had been located. This was greeted with widespread applause. Even the editors of Nature believed that a major piece of the puzzle for schizophrenia had at last been found.

Sadly, the bubble soon burst. Despite many attempts, no one was able to replicate the initial finding, and it is now widely felt to have been a mistake. This is no longer surprising. Use of the restriction fragment length polymorphism approach to finding genes for complex disorders like schizophrenia has been notably unsuccessful. Currently, journal editors are alerted to the receipt of claims that a gene for some disorder has been found, only to be burnt by the next dozen failures to replicate the finding. The schizophrenia “finding” was a great disappointment.

The end of 2001 is unlike any year's end in most of our memories. On September 10, my most serious worry was the chances for my beloved New York Yankees to win their fourth consecutive pennant. The next day, and ever since, that has hardly been a blip on the radar screen of concern. For those of us interested in studying the nervous system, we must remember that the most enduring fallout of the September 11 tragedy is emotional—our population is now a frightened one. Never before has the study of the neuro-science of emotion seemed more important. In subsequent issues, we will have much more to say on this topic.

For physicians and neuroscientists alike, we must also focus on the clinical and research issues that existed before September 11 and will continue to be our responsibility. This issue of CNS Spectrums offers articles on a diversity of topics: epilepsy, genetics, and the treatment of schizophrenia.

Given the wide variety of available antidepressant therapies, an important question is how effective are we in treating depression? In clinical research trials of antidepressants, a treatment response is defined as a 50% or greater improvement in depressive symptoms, whereas remission is defined as having minimal or absent symptoms at the end of treatment. Approximately 50% of patients treated with antidepressants have a treatment response, but only about 25% have a complete remission. Many treatment responders therefore have residual symptoms despite adequate treatment. This is critically important because depressed patients with residual symptoms, even though mild in severity, still have significant functional impairment, have a high risk of relapsing into a more severe episode, and may have a more chronic course of illness. Such patients also do not show a full functional recovery from their depression. Recent comparative studies have found that remission rates are significantly higher with venlafaxine (Effexor) compared to serotonin reuptake inhibitors, which might be due to their different effects on neurotransmitter systems. The use of medication combinations, having additive and/or synergistic antidepressant effects, or adding psychotherapy following a course of pharmacotherapy also can be used to treat residual symptoms and lead to a more complete remission.

There is an old joke that applies to the past–and only the past–of psychopharmacology: One dark night, a police officer notices a man furiously searching for something beneath a street lamp. “What are you looking for?“ he asks. The man replies, “My car keys. If I don't find them, I'll never get home.” “Well,” asks the police officer, “did you lose them here?” “No,” the man replies. “But this is the only place on the block that has any light.”

For example, once it was discovered that tricyclic antide pressants antagonize the presynaptic neuronal reuptake of norepinephrine (NE), the idea was put forth that the problem in depression is some abnormality in noradrenergic function. Some of the tricyclics, like desipramine and nortriptyline, are actually selective NE reuptake inhibitors. However, once it became apparent that selective serotonin (5-HT) reuptake inhibitors (SSRIs) are also effective in treating depression, consideration of the noradrenergic system suddenly disappeared from the literature, replaced by a new hypothesis that depression is caused by deficient serotonergic neurotransmission.

For neurologists and psychiatrists, this month's edition of CNS Spectrums contains both original research articles and review papers surrounding a central theme of enormous importance: how the environment can harm brain function and how the brain can repair itself. We are extremely fortunate to have Jeremy Coplan as our guest editor. Dr. Coplan, with whom I have enjoyed years of collaboration on many projects of mutual interest, is professor of psychiatry at the State University of New York (SUNY) Downstate Medical Center in Brooklyn and senior scientist in the Department of Clinical Psychobiology at the New York State Psychiatric Institute in New York City. Let me now summarize why I believe the area covered this month is so vital.

I am extremely indebted to my Columbia University colleague, Dr. Martha Morrell, for her stewardship of this month's issue of CNS Spectrums. Four of the five articles this month deal with epilepsy, its causes, modern treatments, and potential adverse outcomes of treatment. When I became editor of CNS Spectrums last year, one of my goals was to involve more neurologists in shaping the journal's content. A distinguishing aspect of this goal is to present cutting-edge information of value to both psychiatrists and neurologists. We are, after all, the clinicians and scientists most involved with diseases of the central nervous system, and we even share the same specialty board association. More importantly, however, there have recently been calls for better coordination of training and information between psychiatry and neurology. Dr. Eric Kandel, the recent Nobel Prize winner in physiology, has stated that in some ways the separation of psychiatry and neurology is artificial and impedes both fields. While I do not personally favor a complete merger of the two specialties, I do hope that CNS Spectrums will be one forum for bringing them closer together.

Freud writes in his startlingly innovative book, Wit and Its Relation to the Unconscious, that “…our philosophical inquiries have not awarded to wit the important role that it plays in our mental life.” He pointed out the difficulties of studying the phenomenon scientifically, and went on to analyze the meanings of jokes and why we laugh. He emphasized the “pleasure in economy” that the central nervous system derives from the pithy nature of the witty synthesis. Since then, several authors have brought forward their own theories, Arthur Koestler among them. However, neuroscientists have shown little interest in the subject.

This needs urgent attention. It is therefore welcome that at least one group of scientists is taking jokes seriously. They set up a “Laugh Lab” Web site to investigate humor, and respondents from all over the world were asked to vote for the “best” of several jokes displayed on the site. Their responses will be analyzed and hypotheses tested.