Lighting Nonvisual effects

The rhythmic variations of several hormones in man have been shown to be regulated by changes in the environmental light-dark cycle. In experiments with environmental lightingconditions theseasonal varia tion and the latitude of the study may influence the results. The nonvisual effect of light has recently been used for treating affective disorders. The clinical improvement of some depressed patients from the use of evening bright-light therapy may be related to an effect of light on the melatonin-rhythm generat ing system.

The nonvisual cues of light exert s its effect on the human neuroendocrine function in a rhythmic, circadian-like fashion. One hormone which has a clear 24-h variation and which is tied to the biological clock is the hormone melatonin from the pineal gland. Akerstedt et al (1) showed already 10 years ago that melatonin urinary excretion , bod y temperature, and subjective arousal continued durin g 64 h of sleep deprivation when healthy persons were kept in dim light (lower than 25 cd/m') and unaware of the chronological time. The melatonin-rhythm generating system (see figure  1) thu s shows a biological rhythm which continues in low light for at least 2 d. Somewhat stronger light suppressed the nocturnal increase in melatonin in health y controls in Sweden (2) at a latitude of 59°north. Lewy et al (3) reported that they needed 2500 lx to suppress melatonin when the experiment was done at a latitude of 38°north. Bojko wski et al (4) from England found that most people responded to partial suppression of melatonin with 300 lx when the experiment was performed at a latitude of 51°north .
I mention these differences because they indicate that the results of the effects of light on hormonal concentration and rhythms are influenced by environmental light and that different luminance may exert different effects when studies are don e in different seasons and at different latitudes .

Neuroendocrine changes in affective disorders
Depression belong s to the a ffective disorde rs and is a state of mind with a distinct quality of depressed mood.
Several biological measures have been claimed to be potentially helpful as trait markers in depr ession, to indicate a constitutional (genetic) vulnerability to affective disorders, or as state markers related to the severity of the disease state. Two of the most used tests for state mark ers are the dexamethasone suppression test and the th yroid-stimulating hormone respon se to thyrotropin-releasing hormone .
Melatonin as a possible marker for a subgroup of depression New diagnostic trends emphasize the importa nce of early biological markers for the different subtypes of depression to enable one to choose the right dru g for the individual pat ient. The basis for the interest in melaton in in affective disorders was a report by Wetterberg et al (5) in which higher cortisol levels were seen during depre ssion than during recovery and the peak level of melatonin occurred earlier dur ing the disease stat e.
The potential use of melatonin as a marker in depression was obviou s. Not only is melatonin dependent on both noradrenergic and serotoninergic neuronal systems for its regulation , but melatonin also seems to be related to the hypothalamic-pituit ar y-adre nal axis, which has been shown to be affe cted in depressive states. In addition, melatonin is useful in indicating both the phase and the amplitude of the biological clock. Th e vari ation in melatonin concentr ation over a 24-h period allowed scientists to study the hypothesis of free-running rhythm failur e in subtypes of depr ession and to test the pha se advance theory of a ffective illness introduced in 1968 by Halberg (6). This theor y is based on the possibility of an internal and external desynchronization of physiological functions. Temporal external desynchronization , as in jet lag, occurs in some individuals during flights over time zones, and rapid time-zone changes may even precipitate affective illness in predisposed persons, as Jauhar & Weller (7) showed in London in a study at Heathrow Airport.

Melatonin and seasonal variations
Seasonal variations in the incidence of depression, suicide, and the use of antidepressive therapy are well documented (8,9). Circannual rhythms in pineal function in animals have been reported over the last two decades, and a seasonal variation in pineal gland weights in human autopsy material has been described «2). Seasonal variations in melatonin production, measured as 24-h serum levels, have also been shown, at least at some latitudes (10,11). Serum and plasma melatonin determinations may thus be of interest in relation to different disease states and diagnostic subgroups.
To follow-up early findings of a possible relationship between the pineal gland and adrenal glands, Wetterberg et al (12) reported that low melatonin was related to high cortisol and an abnormal dexamethasone suppression test. The current views of melatonin as a tool in the diagnosis of mental diseases in general was reviewed in 1988 by several authors in the monograph Melatonin, Clinical Perspectives (13). Specific findings relating serum melatonin to clinical variables in patients with depression have also been reported (14-16).

Factors other than light influencing melatonin concentration
It is clear that factors other than changes in the lightdark cycle are of importance for melatonin levels. It has been reported that age (17)(18)(19)(20)(21)(22), body weight (23,24), body height (14), the use of glasses (25), drugs (26), and genetic variation (27) are among factors which in different degrees and under different circumstances may influence melatonin levels in humans. Different types of medication and sampling conditions may also influence melatonin concentrations. In our studies the melatonin radioimmunoassay from KALAB (Danville, California, United States) was used for measuring the melatonin concentration of serum and urine.

Melatonin in depressed patients: effects of light exposure
In previous reports it has been shown that the exposure of healthy persons to a luminance of 350 cd/m' for 1 h between 2200 and 2300 causes a significant suppression of serum melatonin levels followed by a "rebound" to higher melatonin levels later in the night (28). The same experimental paradigm was applied to 12 psychiatric patients with a major depressive episode. In this group the light exposure caused a significant suppression of melatonin levelsat 2300; however, there was less rebound effect (29). Eight of these depressed patients were treated with bright light with a luminance of 350 cd/m' between 1800 and 2000 for 10 d. Some of the depressed patients were rated as improved, while the others did not respond to light therapy. In the responders the suppression of the serum melatonin level by the I-h exposure to light was significant both before and after the light therapy. The melatonin peak appeared to be shifted to later in the night, and the serum melatonin levels were diminished after the 1 h exposure to light following the light therapy.
In summary, bright light has shown, in several studies, to be effective in the treatment of some but not all patients with depression. One attractive theory is that light operates as a time cue to reestablish a normal circadian rhythm in depressed patients whose biological clock is out of phase (30,31). Another question which needs more attention is how healthy persons perform and feel under different naturallight-dark cycles and how manipulation of the environmental lighting in the workplace affects a person's life. New results have provided a theoretical model and a challenge which involves extensive international collaboration to study the effect of light on health and performance. Such studies are called for and have to be carried out at many latitudes. Some are already under way. For those interested in light therapy, an international society for light treatment and biological rhythms has been formed to help to solve some of the many remaining questions involved in the nonvisual effects of light.