UNDER THE MICROSCOPE; Helping the Sad to lighten up in winter

With the encroachment of the season of mists and mellow fruitfulness, another m-word also seems increasingly appropriate: melancholia. People get depressed all year round, but there is something about the end to the easy living of summer that twists the knife in the wound of Monday morning. For some the prevailing mood does indeed match the blackness of the outside: hence the appropriateness of the acronym Sad, "seasonal affective disorder". An "affect" is merely a technical word for a feeling. Why, one might ask, is it a "disorder" to have a perfectly understandable feeling of depression when everything around you is dying and when life is so much less physically comfortable? It is a question of degree. While most of us would like to pull the duvet up instead of going to work, we are not reduced to uncontrollable tears.

Sad sufferers, however, can be helped by an extraordinarily simple procedure."Phototherapy" entails looking at special fluorescent lighting in which the material lining the tubes has been treated to emit all the colours of the spectrum in approximately the same proportions as natural light. A recent survey suggests that, typically, two hours of light exposure in the early morning every day for a week will be effective.

Although the precise conditions for optimising the treatment of Sad are still a matter for debate, it is clear that phototherapy works. Moreover, if chemical sledge-hammering drugs can be substituted for a painless approach, with only very occasional side effects, then the case for phototherapy is very persuasive. How incredible that sitting someone in front of the kind of light that usually comes out of the sky, can alleviate a rainbow of subtle and idiosyncratic problems within the inner world of an individual mind. But aside from the obvious benefits in the clinic, can the success of phototherapy tell us scientists anything about the actual nature, if not the cause, of such debilitating feelings?

A deceptively simple explanation is that it is "all in the mind", that phototherapy works merely because the depressed individual believes that it will: the so called "placebo effect". But this innocent idea is in fact impossible to test scientifically.

If the purported "vital factor" were a chemical, and not light, then it would be a different matter. The procedure would be to give Sad victims an allegedly cure-all pill: however only half the sufferers would actually be receiving the vital factor. If the individuals showing improvement were limited to those who were actually, albeit unwittingly, giving their brain chemicals a kick start with the active agent, then a direct action of the chemical would be suspected. But when the candidate vital factor is daylight, you either see it or you don't: what could possibly be the sneaky equivalent of the sugar pill?

In any case, data so far suggests that there is no single, light-sensitive chemical which throws the happiness switch. The substance that at one time attracted attention is illegal over the counter in Britain, though much hailed in the US as a panacea for a variety of problems ranging from jet-lag to old age: melatonin. This hormone is secreted within the brain in large amounts during the hours of darkness. Herein lies a rationale for combating jet-lag - the melatonin is fooling the brain into thinking that it is night when all the other faithful but conservative body clocks are protesting that it is, after all, day-time. If Sad sufferers had abnormally high levels of melatonin, then the light treatment could be regarded as a restoration of summer and hence as a brake on melatonin production: ergo high melatonin would be the villain. But it turns out that melatonin is not actually to blame for Sad; drugs which prevent the secretion of melatonin do not alleviate the condition.

Even if some other chemical could be implicated, it is a general problem in neuropharmacology to understand the causal link between a chemical and a particular state of mind. In the case of Sad, either light itself triggers a cascade of mood-changing chemicals, or light may activate personal associations of, say, happy summer outings such that it is the activation of memories that set in train a restorative chemical re-balance. The relations between brain chemicals and moods are those of the chicken and egg, the sides of a coin we do not understand. But how reassuring that human idiosyncrasy can trump seemingly even the most obvious of reactions to sunshine. There are a group of people who must be starting to cheer up just about now: "reverse" Sad sufferers, who become depressed at the onset of summer.

! Susan Greenfield is a neuroscientist at the University of Oxford, and Gresham Professor of Physic, London