Seasonal affective disorders: the effects of light on human behaviour

Seasonal affective disorders: the effects of light on human behaviour Leslie Hawkins

It has long been recognized that human moods are affected by seasonal changes: Hippocrates observed that ‘of constitutions some are well or ill adapted to summer, others are well or ill adapted to winter’. It is only comparatively recently, however, that seasonal affective disorders (SAD) have been the subject of serious research. This indicates that mental depression - severe in a small minority of cases - may be related to low exposure to light in the winter months. In many cases phototherapy - which may influence melatonin production - brings relief.

Living systems on this planet depend on light, either directly or indirectly, for their energy source. Green plants convert light energy into carbohydrates, which are then used by animals as a food energy source. The fact that photosynthesis is dependent on light is well known, but it is not so well appreciated that animals too have evolved a variety of mechanisms for directly utilising the sun’s light. Light is, of course, only a small band within the total electromagnetic radiation spectrum emitted by the sun. Radiation with a frequency of around lOI Hz - that is, a wavelength of between 420 and 700 nm - causes the retina of the human eye to be stimulated, and this in turn is translated by the brain into a visual picture of our surroundings. Other animals utilise a slightly wider range of wavelengths, extended particu- larly into the i&a-red region (wavelengths above 700 nm), which allows them to see when to us it appears dark. This rather narrow band of electromagnetic frequencies is therefore called visible light. It provides us with what, until recently, has been thought of as the main function of light, namely to provide us with the sense of vision.

The two main non-visual reactions to light that have been understood for a long while is the synthesis in the skin of Vitamin D - a vitamin essential for the proper metabolism of calcium - and skin tanning. Tanning, which results from the effect of light stimulating the production of a dark pigment, melanin, in the skin, is thought to be a protective mechanism

Leslie Hawkins, BSc., Ph.D., CBiol.. MIBiol., MIOSH.

Is Senior Lecturer in Applied Physiology and Head of the Robens Institute Occupational Health and Safety Service at the University of Surrey. His research interests concern the effects of indoor environments on health with special interest in indoor air quality, lighting and non-ionising electromagnetic radiation.

Endeavour, New Series, Volume 16, No. 3,1393. 0160-6327/62 6500 + 0.00. Pwgamon plag Lid. Ptinled in Gnat Britain.

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against the damaging effect of ultraviolet radiation (wavelengths between 290 and 380 nm) from the sun.

Within the last decade we have come to understand a further, perhaps far reaching, effect of light on physiological control mechanisms - that of control of circadian rhythmicity [I].

Circadian rhythms Virtually all physiological systems ex- hibit periodicity in their activity (figure 1). For example body temperature peaks at about 9 o’clock in the evening and reaches a low value at 4 o’clock in the morning. The difference between the high value and low value is about 1°F (0.6”C). Hormone levels in the blood show similar characteristic rhythms. The adrenal gland produces a peak output of the hormone cortisol at 9 a.m. and this falls progressively throughout the day to a low value at 1 a.m. Mental activity, measured by various performance tasks, shows a rising level of performance throughout the morning to reach a peak around noon. Studies of mental performance have revealed two personality types - larks and owls. Larks rise early in the morning, reach a peak of mental alertness early (before noon), and then decline more rapidly so that they normally go to bed early. Owls, by contrast, rise later, take longer to reach a peak level of performance, and remain more alert in the evening, usually going to bed late. Both types show a characteristic ‘post-lunch’ dip in performance, although this appears to be unrelated to eating at lunch-time [2, 31.

These are given as examples to illus- trate circadian rhythmicity; there are as many rhythms as there are physiological or psychological functions. The interest- ing thing is that each rhythm has a characteristic time to peak and dip, but different body functions peak and dip at different times of the day (figure 2). The closely co-ordinated set of individual rhythms is referred to as ‘internal synchronisation’. The mechanisms that produce periodicity in physiological and

mental function and control their synchronisation have puzzled biologists for a long time. It is known from early experiments that the light-dark period of a normal day and night is an environmen- tal cue which somehow phases the body’s rhythms with the 24 hour period of the Earth’s rotation. M. C. Lobban found that Indians and Eskimos from polar regions, where the alternation of light and dark is reduced, had lower amplitude rhythms (i.e. flatter rhythms) and had evidence of internal desynchronisation [4]. D. T. Krieger and F. Rizzo found similar evidence in partially sighted and blind people [5]. Other experiments concerning people kept in isolation from the natural day-night period have shown that rhythms ‘free- run’ - that is, they are no longer phased to a 24 hour period. Under such conditions most people free-run to a period greater than 24 hours - up to 27 hours in some cases. Additionally, each rhythm free-runs at a slightly different rate, which results in desynchronisation [61.

Such experiments have led to a number of important conclusions about circadian rhythm control.

(1) Each physiological function has its own ‘internal clock’. These so called ‘endogenous’ rhythms can free-run if the body is removed from external cues to the period of the Earth’s rotation.

(2) The most important environment cue is the periodicity of light and dark - this is termed an exogenous rhythm. There are, however, probably other cues which we have learned to use to entrain body rhythms. These include simply a knowledge of time of day, social factors, and regularity of feeding.

(3) The alternation of light and dark produces an enhanced amplitude of rhythms and acts as an external cue to synchronise the individual rhythm. This synchronisation is lost if all external cues are missing, and is greatly dimin- ished if the light-dark cue is removed

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Figure 1 Some examples of circadian rhythms. (a) Rhythm of mental performance comparing larks and owls. (b) The body temperature rhythms. (c) The rhythm of blood cortisol (dotted lines are normal range).

but other cues, such as social factors, remain.

Rhythms of the type we are describing, that occur with a periodicity of about one day are termed circadian. There are, however, others which are also important to many animal species. The monthly menstrual cycle in the human female is an obvious example of a biological rhythm, but we can also recognise circa- annual rhythms (seasonal rhythms) which control breeding patterns and hi- bernation. Although we tend to think that man is unaffected by seasonal changes, as we learn more we may find that we, too, are influenced by the changing seasons. One such possibility, in relation to depressive illness, will be discussed later. The control of circa- annual rhythms is more complex because not only does the period of light and dark vary (according to latitude) but the seasonal variation in climate, particu- larly temperature, also has a strong influence [3].

The pineal gland and melatonin In fish, amphibians, and reptiles, the pineal gland is situated near the skull and contains photoreceptors that respond directly to light entering through the skull bone. In these animals the pineal is sometimes referred to as the ‘third eye’. In man, however, the pineal is situated deep in the brain and contains no active photoreceptors (figure 3). The human pineal receives information on light and dark from the rods and cones in the retina of the eye. It does so through a tortuous nervous pathway that originates in nerve fibres leaving the optic tracts near the optic chiasma. These fibres enter the hypothalamus to constitute what are often called ‘retinohypotbala- mic’ pathways. It is suspected that some control of body rhythms is exerted directly through the influence of the retinohypotlmlamic pathways on hypothalamic functions, because the hypothalamus directly controls a number of physiological functions and indirectly, via the pituitary gland, influences virtually the whole of the endocrine system.

However, this aside, the fibres entering the hypothalamus end up on a group of cells within it called the suprachiasmatic nucleus, and from there relay on to the reticular formation in the mid- brain. Reticula-spinal fibres pass from here down the spinal cord to terminate on a ganglion in the neck, the superior cervical ganglion. This ganglion produces a post-ganglionic (sympathetic) nerve that runs back up the neck to re- enter the cranium and to terminate even- tually on the pineal gland. The nerves synapse via beta adrenergic receptors in the pineal gland, which then influence the activity of N-ace@ transferase, an enzyme regulating the synthesis of melatonin (figure 4). For a detailed descrip-

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Sleep Wakefulness

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Figure 2 Different body rhythms peak at different times of the day. These are normally closely synchronised by phasing them to external cues, in particular the light-dark cycle. If the light-dark period changes the rhythms re-adjust at different rates producing a state of ‘internal desynchronisation’ (jet lag for example).

tion of the biochemistry of indole metabolism in the pineal, the reader is referred to D. C. Klein et al. [7].

The effect of light stimulating the retina is, therefore, to bring about suppression of a number of critical steps in the conversion of serotonin to melatonin. Plasma melatonin levels therefore fall rapidly on exposure of the eyes to light and increase again almost immediately the subject is in the dark. This phenome-

non was fist reported by A. J. Lewy in 1980, who also showed that normal indoor artificial light levels (500 lux) had a relatively insignificant effect, whilst 2500 lux was necessary to produce a characteristic suppression (figure 5) [8].

Seasonal affective disorder (SAD) Affective disorders are broadly defined as states of abnormal mood. Normally the term is limited to the major syn-

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Superior cervlcol ganglion

Preganglionic sympathetic nerve. HP’

cord

Figure 3 The anatomy of the non-visual pathways and the pineal gland.

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dromes of depression and mania although some psychiatrists include anxi- ety states in so far as they are related to depression [9].

During the past decade there has been increasing interest in affective disorders that show a seasonal variation. Perhaps as many as 60 per cent of the population show seasonal changes in sleep or mood but only about 5 per cent have severe seasonal depression that might require treatment. While the majority of those with a seasonal affective disorder have a winter depression, a small number have a smmner depression; a few have depressive episodes in both the summer and winter [9]. The observation that there are seasonal patterns to illness, including depressive illness, has a long historical record. Hippocrates (ca 430 B.C.) taught that the seasons of the year were important in determining disease. ‘It is chiefly the changes in the seasons which produce diseases, and in the seasons the great changes from cold or heat’ [lo]. Hippocrates also observed that ‘of constitutions some are well or ill adapted to summer, others are well or ill adapted to winter’ [lo]. As well as rec- ognizing a general relationship between seasons and disease. Hippocrates and a later Greek physician Aretaeus (ca 15&200) specifically noted a relationship between depression and the onset of autumn and winter [ 111.

The modem interest in seasonal depressive illness probably started with the work of P. Pine1 [12]. He wrote that ‘Maniacal paroxysms . . generally begin immediately after the summer sol- stice’ .

Most of the early physicians including Pinel, and later his student J. E. D Esquirol, considered that temperature was the cause of the depression. Esquirol wrote that ‘heat like cold, acts upon the insane with this difference, that the con- tinuance of warmth augments the excite- ment, whilst cold prolongs the depression’ [13] [14].

However, the idea that light and dark may influence mood was certainly noted by the ancient physicians who, indeed, likened depression to a kind of internal darkness. Amazingly, light therapy to treat depression may have been used in the second century. Aretaeus wrote that ‘lethargies are to be laid in the light and exposed to the rays of the sun (for the disease is gloom)’ [15]. The first modem scientific description of phototherapy was by H. Marx. He reported successful treatment by exposure to artificial light, of soldiers in Northern Scandinavia who suffered recurrent winter depression. He also speculated (in part correctly, as we now know) that the therapeutic effects were mediated by retino-hypophyseal (via retina-hypothalamic) pathways [16]. (These are tracts to the pituitary gland running via the hypothalamus.)

The more recent upsurge in interest in

Tryptophan

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Hydroxy indole ortho methyl tronsferase

I 5-Methoxy Indole UJrlnary SecretIon) 5 - Methoxy Acetic acid Acetic acid

Figure 4 The formation of melatonin and associated indoles from tryptophan in the human pineal. b indicates the steps that are suppressed by light stimulation of the retinohypothalamic pathways which in turn stimulates adrenergic receptors in the pineal.

SAD began in 1982 when Lewy and his co-workers reported a case of winter depression which remitted when they used strong artificial light to lengthen the hours of daylight [17]. These same authors had recently shown that artificial light could suppress melatonin synthesis and they therefore concluded that the anti-depressive effect of phototherapy was due to an increased period of daytime melatonin suppression, similar to that normally experienced in the spring or summer. Since then, a large number of scientific papers have described individual cases or the results of controlled clinical trials, and concluded overwhelm- ingly that bright light is a rapid and effective treatment of winter depression. The literature up to 1988 has been re- viewed by N. E. Rosenthal [18] and by E. Garfield [19]. What are the treatment criteria and how does phototherapy work? A number of treatment variables could influence the effectiveness of phototherapy and these have been inves- tigated in the past few years in some detail. The variables are intensity of light, spectral quality of the light; the duration of exposure; and time of day of exposure.

Consistent with the observations that melatonin suppression requires at least 2000 lux of light intensity, Rosenthal found that light of this intensity was sig- nificantly better at alleviating symptoms than light of 300 lux (which approxi-

mates to normal indoor artificial light levels) [20]. A number of subsequent studies have replicated this finding [e.g. 21, 221.

M. Terman has reported that 10 000 lux is more effective than 2500 lux even if used for only 30 minutes per day [23]. It is quite clear, therefore, that treatment is effective only if bright light is used, and it would seem that above 2500 lux higher intensities can be traded against length of exposure. At 2000 lux most authors have reported that 4 hours exposure is superior to 2 hours or less [e.g. 24, 251. The spectral quality of the light has received rather less attention. R. Wurtman found that in rats the most effective frequency for melatonin suppression was at 520 nm, in the green part of the visible spectrum [l]. Other workers have found that (in the hamster) blue light is most effective [26]. This finding led to an interest in developing and ap- plying full-spectrum lighting in phototherapy. Full spectrum lighting uses fluorescent tubes that emit light that is much closer to the spectral quality of natural sunlight than to the normal fluorescent or tungsten lighting. Full spectrum tubes emit light with more ultraviolet, blue, and green light, and less yellow, orange and red. Although most phototherapy treatments employ full-spectrum lighting there is no experi- mental evidence that this has any greater anti-depressive effect than nor-

mal fluorescent lighting. Time of day of exposure would theoretically be an important consideration. If the effect of phototherapy is to suppress melatonin levels then early morning treatment should be more effective in ensuring a switch over from night-time secretion to day-time suppression.

Indeed, many authors have concluded that morning treatment is most effective [e.g. 27, 281, although some have shown that evening treatment is best [e.g. 29, 301, or that time of day makes no difference [e.g. 311.

In summary, therefore, bright light exposure during the daytime has been found to be an effective treatment for SAD. At least 2500 lux for 4 hours is re- quired, although a higher intensity for lesser periods seems to be as effective and is more practical to administer. Morning exposure is most effective for the majority of sufferers, although time of day seems not to be very critical. There is no evidence that full-spectrum lighting is any more effective than ordinary fluorescent lighting, although this has not been adequately studied.

The mechanisms by which bright light treatment may be effective remain spec- ulative, but are worthy of some discus- sion. There are a number of possibili- ties, which can be summarised as: (1) the melatonin hypothesis; (2) the circadian rhythm phase shift hypothesis; and (3) the circadian rhythm amplitude hypothesis.

Time of day

Figure 5 The suppression of melatonin production by light. Light intensity of 2500 Iux (x) produces a marked suppression whilst light at ordinary indoor levels (o = 500 lux) is almost ineffective. (From: Lewy 1980, Ref. [8].)

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The.melatonin hypothesis The melatonin hypothesis, which in- spired the modem interest in SAD, is not in fact supported very strongly by the current evidence. This hypothesis pro- posed that the shortening day length (photoperiod) during the autumn triggers winter depression by extending the period of night-time melatonin secretion. During the winter months there is a delay in the morning drop in melatonin levels, caused presumably by the low levels of morning light [32]. This length- ening of the nocturnal peak of melatonin will occur in the Northern and Southern hemispheres, but should not occur nearer the equator. There is some evidence that winter depression increases in prevalence and severity with increasing latitude, which would support this hypothesis. There are however a number of pieces of evidence that argue against the melatonin hypothesis. C. Thompson and co- workers have recently found that patients with SAD show an abnormal seasonal variation in sensitivity to light [33]. They appear to be supersensitive in the winter, showing a suppression of melatonin at lower light levels (as had previ- ously been found in patients with manic depression [34]), and subsensitive to light during the summer. This should allow patients with SAD to switch off melatonin secretion more easily in the low light levels of a winter morning, although this appears not to occur.

One argument that would support the hypothesis is that bright light phototherapy administered in the early morning is usually a more effective treatment. The benefit could therefore derive from the switching off of melatonin synthesis at the appropriate time of day and hence shortening of nocturnal peak. However, while light therapy given in the morning and the evening will extend the daytime photoperiod, there is ample evidence that the same dose of light given during the middle of the day, which does not extend the photoperiod, is also effective in many patients [35].

Other arguments against the melatonin hypothesis are that administering melatonin to patients who have had their melatonin lowered by phototherapy does not reverse the benefit of light exposure [36]. Atenolol, a P-adrenergic antagonist, blocks the p receptors in the pineal and causes, like bright light, melatonin suppression. If the melatonin hypothesis is correct therefore, atenolol should be as effective as light in reversing winter depression, although this has been shown not to be the case [37].

While much attention has been paid to melatonin, it must be remembered that it is closely related to serotonin metabolism (figure 4) and serotonin is a power- ful neurotransmitter known to be implicated in depression. The role of serotonin in SAD has barely been inves- tigated [ 3 81. 126

Circadian rhythm phasing An alternative hypothesis that is now gaining more credibility is one which proposes that the shorter winter photoperiod shifts the circadian rhythm phasing. According to this hypothesis, depression occurs when the body’s rhythms are phase-delayed relative to sleep because of the delay in the appear- ance of morning light. If this is the case, then the timing of the melatonin rhythm and other body rhythms, becomes more important than their amplitude. Phase delayed melatonin rhythms occur in normal subjects in dark winter conditions; the suggestion is that patients with SAD are more readily phase delayed that others [39]. The benefits of morning phototherapy are to advance the onset of night- time melatonin production and to correct the phase delay. This explains the effectiveness of morning therapy, but the ap- parent benefit of exposure to light at other times of the day, especially the evening which would further delay the rhythm, argues against the hypothesis. Thompson has suggested that when the melatonin rhythm ,begins to delay, the suprachiasmatic nucleus increases the individual’s light sensitivity in order to compensate. This increased light sensitivity in SAD patients was commented on earlier [34]. Depression, it is suggested, occurs when the increased sensitivity still fails to restore the appropriate phase relationship [ 331.

Circadian rhythm amplitude Finally, the circadian rhythm amplitude hypothesis suggests that the low levels of winter light flatten circadian rhythms (reduce their amplitude). Consistent with this hypothesis is the observation that in depression (of all types) there are abnor- mally low circadian rhythm amplitudes [ 133, and in winter depression they are especially so [31]. Phototherapy has the effect not only of phase shifting the rhythms (dependent on the timing of the exposure) but also of increasing the amplitude. The amplitude hypothesis is a relatively simple explanation, but has not yet been tested experimentally.

Whatever the explanation, there is no doubt that humans are affected by a circa-annual rhythm of mood. For most of us this is no more than a reduction in mood during the dark days of winter, but for about 5 per cent of the population this can manifest as a disabling and deep depression lasting for three or four months of the year. The explanation for this will be somewhere in our understanding of chronobiology. The relation- ships of the retina, the hypothalamus, the suprachiasmatic nucleus, the pineal gland and its hormones, especially melatonin, are clearly involved in an intrigu- ingly complex fashion. Fortunately, we know that phototherapy treatment for most sufferers is a relatively simple and effective means of remission. The expe-

riences of phototherapy, however, especially the relative unimportance of the time of day it is given, has confounded rather than helped our understanding of the aetiology of the disease.

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Seasonal affective disorders: the effects of light on human behaviour

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