(New Scientist) -- Lung cancer, hypertension, heart disease, birth defects - we're all too familiar with the perils of smoking. But add to that list a frightening new concern. Mental illness. According to some controversial new findings, if smoking doesn't kill you, it may, quite literally, drive you to despair.

The tobacco industry openly pushes its product as something to lift your mood and soothe anxiety. But the short-term feel-good factor may mask the truth: that smoking may worsen or even trigger anxiety disorders, panic attacks and depression, perhaps even schizophrenia.

Cigarettes and mental illness have always tended to go together. An estimated 1.25 billion people smoke worldwide - including roughly a quarter of Britons and Americans. Yet people who are depressed or anxious are twice as likely to smoke, and up to 88 percent of those with psychotic disorders such as schizophrenia are smokers. A recent American survey concluded that around half of all cigarettes burn in the fingers of those with mental illness.

But the big question is why? The usual story is that the illness comes first. Mentally ill people take up smoking, or smoke more, to alleviate some of their distress. Even when smoking seems to start before the illness, most doctors believe that early but invisible symptoms of the disorder spark the desire to light up. But perhaps something more sinister is going on.

A growing band of researchers claim that smoking is the cause, not the consequence of clinical depression and several forms of anxiety.

"We know a lot about the effects of smoking on physical health, and now we are also starting to see the adverse effects in new research on mental illness," says epidemiologist Naomi Breslau, director of research at the Henry Ford Health Care System in Detroit.

Breslau was one of the first to consider this heretical possibility. The hint came from studies, published in 1998, which followed a group of just over 1,000 young adults for a five year period. The 13 percent who began the study with major depression were around three times more likely to progress from being light smokers to daily smokers during the course of the study, though there was no evidence that depression increased the tendency to take up smoking. But a history of daily smoking before the study commenced roughly doubled the risk of developing major depression during that five-year period. Smoking, it seems, could predate illness.

At first Breslau concluded that whatever prompts people to smoke might also make them depressed. But as the results of other much larger studies began to back the statistical link, she became more convinced than ever that what she was seeing were signs that smoking, perhaps the nicotine itself, could somehow affect the brain and cause depression.

One of these larger studies was led by Elizabeth Goodman, a pediatrician at the Children's Hospital Medical Center in Cincinnati. She followed the health of two groups of teen-agers for a year. The first group of 8,704 adolescents were not depressed, and might or might not have been smokers, while the second group of 6,947 were highly depressed and had not been smokers in the past month.

After a year her team found that although depressed teen-agers were more likely to have become heavy smokers, previous experimentation with smoking was the strongest predictor of such behavior, not the depression itself. Crucially though, teen-agers who started out mentally fit but smoked at least one packet per week during the study were four times more likely to develop depression than their nonsmoking peers. Goodman says depression doesn't seem to start before cigarette use among teens.

"Current cigarette use is, however, a powerful determinant of developing high depressive symptoms."

True, it's a disturbing statistical correlation. But just because smoking starts before depression, does that make it the cause? Couldn't the traditional interpretation, that people use cigarettes to self-medicate, still hold true?

Indeed, lots of anecdotal evidence suggests smoking comes before the illness in most people with schizophrenia. But equally, plenty of data shows that smoking damps down the side effects of schizophrenia drugs and even eases some of the symptoms. Since they started noticing the trend for smoking to predate depression and to some extent schizophrenia, other researchers have taken a hard look at epidemiological data on other mental health conditions.

Karen Lasser of the Cambridge Hospital and Harvard Medical School in Boston published a large-scale study a little over a year ago detailing the smoking habits and mental health of almost 4,500 people between the ages of 15 and 54. She says her findings confirm the idea that mental illness encourages smoking. But she also found that smokers had a higher risk of subsequently developing depression, panic attacks and longer-term anxiety disorders such as agoraphobia. She shares Goodman's feeling that we can't ignore the obvious implication, that smoking is a cause rather than a consequence of these problems.

Breslau, too, finds that smokers are as much as four times more likely to have an isolated panic attack and three times more likely to develop longer-term panic disorder than nonsmokers. It's a hard message to get across, because many smokers say they become anxious when they quit, not when they smoke. But Breslau says this is a short-lived effect of withdrawal which masks the reality that, in general, smokers have higher anxiety levels than nonsmokers or ex-smokers. Not only that, but anxious people, she found, were no more likely to take up smoking after their symptoms developed than people without their problems. That's enough to convince Breslau that cigarettes may be triggering the problem.

Inevitably it will take more than suspicion and statistics to prove the link. But a more detailed look at anxiety disorders has only fanned the flames. Both Breslau and Jeffrey Johnson of New York State Psychiatric Institute at Columbia University find that certain mental conditions are linked with breathing difficulties that might be triggered or at least exacerbated by smoking.

Johnson and his team found that people in good mental health who smoked a packet or more of cigarettes a day at age 16 were 16 times more likely to develop panic disorder, 7 times more likely to become agoraphobic and 5 times more likely to develop generalized anxiety disorder (GAD) than people who stuck to less than one pack a day. And because anxious adolescents weren't any more likely than non-anxious teen-agers to become adult smokers, it's more likely that smoking is a cause, not a consequence, says Johnson.

Smoking, says Johnson, seems to be associated with exactly the group of anxiety conditions that have recently been found to be linked to respiratory disorders. And conditions that are not linked with smoking - such as obsessive compulsive disorder or social anxiety disorder - are probably not affected by breathing problems either. This, he believes, is the key to why smoking can affect the mind.

Smoking can mess up breathing to such an extent that it triggers a condition called "false suffocation," says Donald Klein, one of Breslau's colleagues. It's the high levels of carbon monoxide in cigarette smoke that are responsible. And this feeling leads to panic. Breslau points out that serious lung disease may also trigger feelings of suffocation and raise the risk of panic attacks.

Johnson believes that panic attacks caused by breathing difficulties that are triggered or heightened by smoking could play a role in longer-term anxiety disorders too. But breathing difficulties aren't the only problem with smoking. He also believes the stimulant effects of nicotine itself could play a part. The state of high arousal, rapid breathing and heart rate and raised blood pressure, especially in people who chain-smoke, may be indistinguishable from anxiety.

And we do have other reasons to believe that nicotine can influence the brain directly. David Balfour, professor of behavioral pharmacology at Dundee University and an expert on nicotine's action on the brain, says that large amounts of nicotine make rats more anxious. Balfour is not convinced, however, that epidemiological studies go far enough to show that smoking is a cause rather than a consequence of mental illness.

"People with schizophrenia may use chronic exposure to nicotine to normalize the mechanisms which underlie the disease."

Copyright 2002 New Scientist. All rights reserved.