Psychiatry Research, 43:299-302 Elsevier

299

Letter

Pupillometry in Identical Twins

To the Editors:

Pupillary variables and their responses to pharmacological challenges have been used m psychiatric research by various investi- gators (for review. see Sitaram et al., 1983). There have been only a few studies that looked at the genetic aspects of these varia- bles. In a study of the effect of physostigmine and pilocarpine on the iris sphincter in normal subjects, Lowenstein and Loewenfeld (1953) included a pair of identical twins. The pupillary contraction and redilatation in response to 1% solution of pilocarpine were similar in the twin pair. Bertler and Smith (1971) studied the resting pupillary diameter in 10 pairs each of monozygotic and di- zygotic twins. Monozygotic twins showed significantly higher correlations for the resting diameter and marginal correlations for the phenylephrine response. Dizygotic twins did not show any correlation.

Here we report preliminary data from 11 identical twin pairs who underwent pupil- lometry in our laboratory. The twins were part of a larger group of subjects who participated in a battery of tests including polysomnographic, electroencephalographic, and evoked potential studies. All the twins (all women, mean age = 48.8, range = 28-72) were physically healthy as confirmed by history, laboratory tests (sequential multi- channel autoanalyzer-12, triiodothyronine, thyroxin, and urinalysis), and electrocardio- gram. There was no past or present history of any major psychiatric illness. The subjects were not taking any medications. Zygosity was confirmed by blood grouping in eight pairs and by DNA typing in three pairs.

To control for the circadian variation in pupillary diameter, the pupillometric examina- tion was uniformly scheduled for the morning after the subject’s arrival in the clinic. An infrared sensitive binocular tele- vision pupillograph that detects pupil size electronically with a resolution of about k 0.05 mm was used. The output from the pupil- lograph was plotted on graph paper that was running at a speed of 10 mm/ second with an amplitude scale of 1 mm/cm on a recorder (Gould TA 600). The subject was seated in front of the pupillograph with the head positioned comfortably on the chin rest. With the lights turned off, the subject was asked to look at a red fixation light at 2 meters in front and 15 degrees above the line of vision. For the recording of pupillary reflexes, the following procedure was used: The subject was allowed to blink at her natural rate except for the immediate period after hearing a beeping noise. Ten beeps were presented with an interval of 10 seconds between each one. One second after the beep, the eyes were exposed to a l-second light flash with an intensity of 15 foot-candles. A Sylvania glow modulator tube was used as the source of white light. For the recording of a darkness reflex, the 15 foot-candle stimulating light was turned on. After about 25 seconds of adaptation to this light, the pupils were stimulated to dilate by a series of “dark flashes.” Ten interruptions of light every 4th second (1 second lights off and 3 seconds lights on) served as dark flashes. The darkness reflex is a test of the integrity of the peripheral sympathetic tone of the iris dilator

0165-1781/92/$05.00 Q 1992 Elsevier Scientific Publishers Ireland Ltd.

300

muscle. After the recording of the pupillary and darkness reflexes as described above, the lights were turned on. The pupillary diameter was continuously measured for a period of 5 minutes during which time the subject was instructed to keep blinks to a minimum and to keep looking at the fixation light. This part of the experiment was conducted to look at the fluctuations of the pupillary diameter over a short period of time.

The following observations were made from the data collected:

1. The 10 tracings of the pupillary reflexes were visually examined and blink artifacts, if present, were rejected. The tracings were superimposed on each other to get the tracings shown in Fig. 1. The same procedure

Fig. 1. Pupillaty reflex in identical twins

was followed for the darkness reflexes (Fig. 2). Tracings from each twin pair are shown side by side. As can be appreciated visually, the morphological patterns of the pupillary reflexes and darkness reflexes are strikingly similar between twins.

2. The maximal change in pupillary diameter was measured for each trial of the pupillary reflex. These were averaged for the 10 trials to get an average for each subject. Table 1 shows the values for the 11 twin pairs. The intraclass correlation (McNemar, 1955) was 0.96 (p < 0.001).

3. The average change in pupillary diameter during the darkness reflex was also calculated for all twin pairs (see Table 1). The intraclass correlation was 0.80 (p < 0.001).

Fig. 2. Darkness reflex in identical twins

301

4. The peak velocity of the pupillary con- striction during the light reflex was measured manually from the graph and was averaged from all the tracings of each subject (see Table 1). The intraclass correlation of the averaged peak velocity between twins was 0.76 @ < 0.01).

5. From the continuous tracing of the pupillary diameter, the values at every second were extracted with a digitizer. These values were used to get an average pupillary diameter for the 5-minute period. Table 1 shows the values for 10 of the 11 twin pairs. The pupillary diameter showed a high intraclass correlation (0.96, p < 0.001) between twins. Data from one pair were lost due to technical reasons.

A more robust nonparametric correlation measure (Spearman rank order correlation) was also used. Table 1 presents the results.

The preliminary data are suggestive of genetic determination of the dynamic components of some pupil variables. A larger study including monozygotic and dizygotic twins would be needed to assess the degree of genetic versus environmental contributions.

Acknowledgments. The authors thank Dr. Irene Loewenfeld for the supervision of the pupillographic measurements and the data analyses. The research reported was partially supported by grants PSO AA-0761 1 and MH-42230.

Table 1. Pupiilary variables in twins

Change in Change in pupiiiary pupiiiary Peak diameter diameter speed of (in mm), (in mm), pupiiiaty Average

Twin pupiiiaty darkness contractions PUPii

pair reflex reflex (cm/set) diameter

no. Twin A Twin B Twin A Twin B Twin A Twin B Twin A Twin B

1 1.96 2.37 0.47 0.38 4.16 4.89 6.74 2 1.87 1.89 0.60 0.42 3.78 3.90 5.77

3 1.01 1.27 0.03 0.05 2.27 2.50 6.92

4 0.94 1.46 0.05 0.17 2.45 2.81 4.32

5 0.84 0.88 0.07 0.06 2.50 2.57 5.90 6 1.10 1.38 0.35 0.06 3.75 4.71 5.59 7 0.36 0.75 0.06 0.05 1.81 1.93 6.23 8 0.92 0.57 0.07 0.05 3.38 2.05 5.70 9 1.21 0.55 0.47 0.55 2.66 1.61 3.97

10 3.03 2.69 0.67 0.45 1.78 3.68 5.00 11 1.58 1.60 0.07 0.05 3.91 4.07

Mean 1.35 1.40 0.26 0.21 2.95 3.16 5.61 SD 0.73 0.71 0.25 0.20 0.87 1.14 0.95

6.50

6.49

6.23

4.90

5.45

6.01

5.40

5.40

4.84

5.61

5.68

0.60

F

lntraclass

correlation

p (2-tailed)

Spearmanrank order correlation

p (Btailed)

48 9 7.30 54

0.96 0.80 0.76 0.96

<O.Ol <O.Ol <O.l <O.OOl

0.76 0.76 0.60 0.64

<0.007 <0.007 <0.05 <0.04

302

References

Bertler, A., and Smith, S.E. Genetic in- fluences in drug responses of the eye and heart. Clinical Science, 40:403-410, 1971.

Lowenstein, O., and Loewenfeld, I. Effect of physostigmine and pilocarpine on iris sphincter of normal man. Archives of Ophthalmology, 50~31 l-318, 1953.

McNemar, 0. Psychological Statistics. 2nd ed. New York: John Wiley & Sons, 1955. pp. 249-39 1.

Sitaram, N.; Jones, D.; Kelwala, S.; Bell, J.; Stevenson, J.; and Gershon, S. Pharmacolo- gy of the human iris: Development and use of reliable challenge strategies in the study of depression and antidepressant response. Progress in Neuropsychopharmaeology and Biological Psychiatry, 7:273-286, 1983.

K.C. Joseph, M.D.’ Department of Psychiatry Wayne State University School of Medicine Detroit, MI.

Reba Baker, R.N. Joe C. Christian, M.D., Ph.D. John I. Nurnberger, Jr., M.D., Ph.D. Department of Psychiatry Indiana LJniversity School of Medicine Indianapolis, IN

Natraj Sitaram, M.D. Department of Psychiatry Wayne State University School of Medicine Detroit, MI.

1. Reprint requests to Dr. K.C. Joseph, Detroit Psychiatric Institute, 115 1 Taylor, Detroit, MI 48202, USA.