www.elsevier.com/locate/jad

Journal of Affective Disorders 78 (2004) 153–156

Brief report

The effect of bright light exposure on pupillary fluctuations in

healthy subjects

Zoltan Szaboa,*, Zsolt Tokajib, Janos Kalmana, Laszlo Oroszib, Aniko Pestenaczb,Zoltan Jankaa

aDepartment of Psychiatry, Albert Szent-Gyorgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged,

Semmelweis u.6, Szeged H-6725, Hungaryb Institute of Biophysics, Biological Research Center, Szeged, Hungary

Received 6 March 2002; received in revised form 24 June 2002; accepted 5 July 2002

Abstract

Background: Light therapy is thought to be the first choice treatment of winter depression. However, its way of action is

poorly understood. In order to find a solid effect of bright artificial light, we studied its possible alerting action through the

spontaneous fluctuations of the pupil, considered to be an objective measurement of vigilance. Methods: Pupillary fluctuations

of 10 healthy subjects (mean age: 22F 1 S.D. years) were measured for 60 s before and 15 min after 0.5 h, 10 000-lux light

exposure. The cumulative change in pupil size, characterised by the pupillary unrest index (PUI) decreased at each subject, and

this decrease was in average 35F 4.4% S.E.M. The average pupillary diameters were unchanged (101F 2.2% S.E.M.). This

analysis revealed that the slow components of the pupillary fluctuations also decreased considerably. Limitations: There was no

dim light or other placebo control of the light treatment. Conclusions: Bright light exposure significantly influenced the

pupillary fluctuations. We suppose that bright light exposure increases the level of alertness, and this could be a possible way by

which bright artificial light exerts a beneficial effect also in affective disorders.

D 2004 Elsevier B.V. All rights reserved.

Keywords: Alertness; Pupillary oscillation; Pupillography; Seasonal affective disorder

1. Introduction

Light therapy is a simple and rapidly acting method

that is proved to be effective in winter depression and

in other affective disorders as augmentation therapy

(Terman et al., 1998; Lam and Levitt, 1998). The

0165-0327/$ - see front matter D 2004 Elsevier B.V. All rights reserved.

doi:10.1016/S0165-0327(02)00241-0

*Corresponding author. Tel.: +36-62-545-791; fax: +36-62-

545-973.E-mail address: szaboz@nepsy.szote.u-szeged.hu (Z. Szabo).

significant role of serotonin in the pathophysiology of

winter depression is well known (Szadoczky et al.,

1989; Neumeister et al., 1997), and tryptophan deple-

tion blocks the effect of light therapy. The influence

on the circadian phase is also important in the anti-

depressant effect of light. Light has an influence on

the suprachiasmatic nucleus (SCN), known as the

‘biological clock’, which sends an alerting signal to

the cortex (Daan et al., 1984; Edgar et al., 1993).

However, the SCN-dependent alerting effect was

found to be intact in seasonal affective disorder

Z. Szabo et al. / Journal of Affective Disorders 78 (2004) 153–156154

(SAD) patients (Cajochen et al., 1995). It is pertinent

to mention here that the recurrently emerging expla-

nation is that light therapy can be an elaborate placebo

(Wileman et al., 2001; Avery et al., 2001). This is the

reason why it would be important to find a biological

effect of light therapy.

The effect of light treatment on the level of

alertness has rarely been studied. However, there are

some evidences that light has an alerting effect, and

that this can be an important component of the

efficacy of light therapy (Partonen, 1994; Partonen

et al., 1996). Moreover, bright light exposure

improves vitality and alleviates distress in healthy

subjects (Partonen and Lonnqvist, 2000).

Hippus means the continuous changing of the

pupillary diameter in dark or constant intensity of

light. Changes in the size of the pupil probably

reflect the activity of the autonomous nervous

system (Calcagnini et al., 2000), the emotional state

and also cognitive functions (Grunberger et al.,

1996, 1999).

There are two basic observations about the extent

of the pupillary fluctuations. First, that it correlates

with the extent of alertness in healthy subjects (Wil-

helm et al., 1998), or in patients with sleeping prob-

lems (Newman and Broughton, 1991). The other is

that it increases parallel to cortical activation in

cognitive tasks, and drops in diseases with cortical

activity deficit (Grunberger et al., 1996, 1999).

Spontaneous changes in pupil size in the dark are

connected with alertness. After dark adaptation low

frequency and high amplitude waves, called ‘fatigue

waves’ can be observed. The power of fluctuations

also increases with sleepiness (Lowenstein et al.,

1963; Ludtke et al., 1998; Hunter et al., 2000). With

decreasing alertness, the amplitude of the fatigue

waves increases. Furthermore, pupillographic sleepi-

ness test has been found as a sensitive tool to measure

drug-induced changes in the level of arousal (Phillips

et al., 2000a,b). The simplest way to characterize the

extent of the pupillary oscillations is the measurement

of the cumulative changes in pupil size, which is

called pupillary unrest index (PUI) (Ludtke et al.,

1998).

In the present study we examined the effect of

bright light on pupillary fluctuations of healthy sub-

jects in order to obtain data about the putative influ-

ence of light exposure on alertness.

2. Subjects and methods

2.1. Subjects

We made measurements on 10 healthy (according

to Mini International Neuropsychiatric Interview,

Lecrubier et al., 1997) non-smoker and drug-free

subjects. The average age was 21F1 S.D. years.

The male–female ratio was 4:6.

2.2. Method

2.2.1. Light exposure

A standard 10 000-lux light box (Alaska Northern)

was used. The duration of the light treatment was 30

min between the period of 08:00 to 10:00 h. The

subjects were told to look into the lamp at least five

occasions per minute but not continuously.

2.2.2. Measurement of pupillary oscillations

The subjects with head fixed by a chin and

forehead-rest were fixating at 1-m distance to a red

light emitting diode. The measurements were per-

formed at a constant level of light conditions of 80

lux.

After adaptation, the pupillary fluctuations (left

eye) of the subjects were recorded for 60 s from 25

cm distance by a Sony CCD TR427 video camera

recorder equipped with a lens of 30 cm focus. The

pupillary recordings were digitalized off-line at 10

frames/s repetition rate by a capture card (PCTV

Rave, Pinnacle System) of a Pentium II computer.

The resolution was set to 384� 288 points.

The frames were processed by automatic software

(Pupillator 4.0) developed in our laboratory.

We determined the pupillary unrest index (PUI) as

the cumulative change in pupil size during 60 s. We

recalculated each data point of the pupillary kinetics

as the average of four subsequent data points. Fol-

lowing this analysis, we determined how the cumula-

tive changes in pupil size depend on the interval of

averaging. This serves as an alternative of the Fourier-

transformation. On the other hand, this does not

require the hypothesis that the pupillary fluctuations

might be periodic in time, and as described in the text,

it serves some useful, and easily comprehensible

information about the faster and slower components

of the pupillary fluctuations.

Z. Szabo et al. / Journal of Affective Disorders 78 (2004) 153–156 155

The significance levels of our findings were defined

according to Dunn and Everitt (1995) by determining

the confidence intervals using the table of t-distribution.

Fig. 1. The cumulative change in pupil size as the function of the

length of the averaging interval used for smoothing expressed (a) as

amplitudes, and (b) as post-treatment decrease in percent. The solid

and dashed lines in (a) show the average curve for the subjects

before and after light exposure, respectively. The solid line in (b)

represents the average of the 10 subjects. The dashed lines show the

averages of 5–5 subjects separated by chance.

3. Results

We analysed the change of the pupillary unrest

index before and after single light treatment. The

changes were highly significant (t = 4.48, P < 0.001).

In each subject, we found decrease in PUI (in

average 35F 4.4% S.E.M.), in eight cases the de-

crease was above 30%. The average pupillary di-

ameter remained almost unchanged (100.8F 2.2%

S.E.M.). The frequency components of the pupillary

fluctuations were studied by smoothing the pupil-

lary diameter kinetics by averaging the data points

in interval selected from 0.4 to 10 s range. Fig. 1a

shows the cumulative change in the pupil size

before and after light exposure versus the duration

of the interval of averaging. At all frequencies a

decrease after light exposure can be detected. We

can see larger decrease at high frequencies but also

at low ones it remains above 20%. Fig. 1b shows

the decrease of the cumulative change in pupil size

in time spectrum analyses. We divided the subjects

randomly into two groups and repeated the analyses

with the same results. By this method we found a

curve characterized by three peaks at specific

frequencies.

4. Conclusions

Our data showed that light exposure causes a

significant decrease of pupillary oscillations. Consid-

ering the connection between the change of the

pupillary fluctuations and the alertness, the results

suggest that single bright light used standardly in

medical treatment strongly and promptly influences

alertness. We found this significant effect in healthy

subjects but we can suppose the importance of this

alerting effect also in winter depression, explaining

the efficacy and rapid remission rate seen in connec-

tion with light therapy, which may support the SCN-

dependent alerting effect of the light.

The decrease of the PUI showed a specific frequen-

cy response curve. This indicates that the decrease in

the pupillary fluctuations is also characteristic of the

slow components. This frequency analysis contains

specific fine structures of unknown origin. Since we

observed similarly unique and reproducible curves for

some nootropic drugs (unpublished data), our idea is

Z. Szabo et al. / Journal of Affective Disorders 78 (2004) 153–156156

that the frequency curves calculated this way could

preliminarily be suggested as fingerprints.

Acknowledgements

This work was supported by ETT T04/59/2000

grant.

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