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Spontaneous eye blink rate in winter seasonal affective disorder
P.~_vchiatr.v Research, 4717945 Elsevier
Spontaneous Disorder
79
Eye Blink Rate in Winter Seasonal Affective
Giuseppe Barbato, Douglas and Dan A. Oren
E. Moul, Paul Schwartz,
Norman
E. Rosenthal,
Received June 24, 1992; revised version received January 12, 1993; accepted January 26, 1993.
Abstract. We investigated spontaneous eye-blink rates in 19 drug-free patients with winter seasonal affective disorder (SAD) and 18 normal control subjects. At baseline, there were no significant differences between the two groups (mean + SD blink rate: lS/minute * 8 vs. IS/minute + 7). Light therapy (10,000 lux: I hour each morning for 1 week) produced no significant change in mean (4 SD) blink rates either in 10 SAD patients (13/minute + 8 vs. IO/minute f 7) or in 12 normal control subjects (15/minute f 6 vs. 14/minute + 6). A post hoc exploratory analysis of the effect of light therapy on premenopausal female subjects (5 patients and 9 control subjects) showed a significant decrease in mean (& SD) blink rate in the patients after treatment (17 + 6 vs. 12 f 8 compared with 15 5 7 vs. 16 + 5). These results do not support the idea that an elevated blink rate may be a general biological marker in SAD, but they suggest a possible link between light treatment and mechanisms that regulate blink rate in premenopausal SAD patients. Key Words.
Depression,
light
therapy,
circannual
rhythms,
treatment,
sex
differences.
Spontaneous
eye blinks
less than one-half stimuli (Karson,
are defined
second,
that
as bilateral
occur
brief eye closures,
continually
and
in the
which absence
usually
last
of external
1983). The frequency-normally IO-20 blinks/ minute-is not related to immediate physiological needs of the ocular system, since only two to four blinks every minute are necessary to prevent cornea1 drying (Norn, 1969; Doane, 1980). Several studies suggest that blink rate is associated with central dopaminergic function. Blink rate is decreased in Parkinson’s disease (Hall, 1945; Karson, 1983) a disorder of dopamine deficiency, while it is increased in schizophrenia (Stevens, 1978~; Karson et al., 19816; Mackert et al., 1990) a disorder in which increased dopaminergic function is hypothesized. Blink rate is also increased in levodopainduced dyskinesia and decreased by neuroleptic treatment (Karson, 1983; Kleinman et al., 1984; Bartko et al., 1990; Mackert et al., 1990).
Giuseppe Barbato,
M.D., is Visiting Fellow; Norman E. Rosenthal, Environmental Psychiatry; Douglas E. Maul, M.D., Paul Schwartz, M.D., Senior Clinical Investigators, Clinical Psychobiology Branch, National Bethesda, MD. (Reprint requests to Dr. D.A. Oren, Clinical Psychobiology Mental Health, Bldg. 10, Rm. 4S-239, Bethesda, MD 20892, USA.) 0165-1781/93/$06.00
@ 1993 Elsevier Scientific
Publishers
Ireland
Ltd
M.D., is Chief. Section on and Dan A. Oren, M.D., are Institute of Mental Health, Branch, National lnstitute of
80 Recently, Depue et al. (1988) reported an increased eye-blink rate in four premenopausal women with winter seasonal affective disorder (SAD) compared with four premenopausal control subjects. Light therapy normalized the elevated blink rate. These data suggest that an elevated blink rate may be a state marker in SAD. Depue et al. (1990) extended their sample to a total of 17 premenopausal patients and 11 premenopausal control subjects, and confirmed the increase of blink rate in SAD patients. Paradoxically, 11 patients who were also studied during summer remissions showed no significant difference in blink rate between winter and summer, thereby suggesting that blink rate is a trait marker in SAD. Depue et al. (1990) proposed that the elevated blink rate might result from a compensatory up-regulation of dopamine D, receptors involved in the eye-blink system secondary to reduced functional activity of dopamine. The clinical and biological features of winter SAD support the hypothesis that dopaminergic systems may be disturbed in the disorder. SAD symptoms include psychomotor retardation and loss of energy, both of which could be behavioral manifestations of dopaminergic deficiency (Beninger, 1983; Depue and Iacono, 1989). Depue et al. (1989) found lower prolactin levels in SAD, and Arbisi et al. (1989) reported diminished responses to thermoregulatory challenges in SAD-both of which may be expressions of dopaminergic alterations in winter SAD. The present study was designed to analyze the blink rate and the effect of light therapy in a larger and more varied sample of winter SAD patients and control subjects than has been studied previously, with the aim of better assessing to what extent this abnormality may be a general feature of the condition and a possible clue to disturbed dopaminergic functioning.
Methods The study was conducted between November II, 1990, and March 13, 1991. Nineteen winter SAD patients (5 men, 14 women; mean age = 38 years, SD = 7) and IS normal control subjects (4 men, 14 women; mean age = 37 years, SD = 6) were recruited through advertisements and referrals. The patients had a winter depression history of 15 (SD = IO) years. Eighteen out of 19 patients had individually age- and sex-matched controls. All subjects were evaluated with the Structured Clinical Interview for DSM-III-R(SCID-R; Spitzer and Williams, 1986). Diagnosis of winter SAD was established on the basis of the criteria of Rosenthal et al. (1984). Of the 19 patients in our study, I I had no history of any previous psychotropic drug treatment and only two had received an antidepressant medication in the 7 months before the study. All subjects had been drug-free for at least 2 weeks before entering the study and remained drug-free for the duration of the study. No subject had received fluoxetine in the 6 weeks before the study. Patients had no concurrent Axis 1 psychiatric illness. Control subjects had no history of Axis 1 psychiatric illness. All subjects had normal physical examinations and routine laboratory screening before testing and had no significant medical, neurological, or ophthalmological illness. Subjects who were wearing contact lenses or who were suffering at the time of testing from a cold, flu, headache, or any condition interfering with visual sensitivity to light were excluded. All subjects gave informed consent. The two groups were studied before and after I week of 10,000 lux light treatment administered by having the subject sit I foot from a light source (Sunbox@) for I hour each morning. On the days of eye-blink testing, the Structured Interview Guide for the HamiltonSeasonal Affective Disorder version (SIGH-SAD; Terman et al., 1991) was used in the assessment of the severity of depressive symptoms by a rater who had no knowledge of
81 treatment condition. The SIGH-SAD incorporates the Hamilton Rating Scale for Depression (HRSD) and the supplementary atypical symptoms characteristic of SAD (Rosenthal and Heffernan, 1986). At the time of study entry, the patients had been clinically depressed for a mean of 6 (SD = 2) weeks. Vertical and horizontal electro-oculograms (EOGs) were recorded on a Grass 78-D polygraph. Gold skin electrodes were placed 3.0 cm above and 2.0 cm below the left eye as measured from the center of the pupil to the center of the electrode (vertical EOG), and at the outer canthi (horizontal EOG). An eye blink was defined as a sharp high amplitude wave > 100 PV and < 400 msec in duration (Depue et al., 1988, 1990). Polygraphic records were obtained between 2 p.m. and 5 p.m. in an air-conditioned room with indoor light of 150 lux at the level of the subject’s eyes. Each subject had 10 minutes to become adjusted to the recording room and light environment. During the recording, each subject sat silently in front of a blank, neutral wall. The subject was asked to remain awake, so that we could study basal ocular activity. No subject fell asleep during the recording session. Eye-blink rate was taken as the mean number of blinks that occurred during the first 2 consecutive minutes after a 5-minute accommodation period. Subjects were unaware of the accommodation period. Comparisons before treatment were made with unpaired f tests. Analysis of variance (ANOVA) with patients vs. subjects as a grouping factor and before vs. after light therapy as a repeated measure was used to study blink rates of those who completed the course of phototherapy. Correlations between blink rate and degree of clinical symptomatology were determined using the Pearson coefficient correlation (r). To focus on a group similar to that studied by Depue et al. (1988) a post hoc analysis of data was performed on premenopausal women (12 patients and 13 controls). Results are presented as mean + SD.
Results Before light treatment, the mean eye-blink rates for the winter SAD patients (n = 19) and control subjects (n = 18) were (Table 1) 15/minute f 8 and IS/minute + 7 (t = 0.23, df = 35, p > 0.9) respectively. SAD patients showed no significant correlations between eye-blink rates and the severity of depression, either when the 21-item HRSD score (r = 0.22, p > 0.4) or the atypical symptom score (r = 0.15, p > 0.5) was considered. Eye-blink rate was not significantly correlated with psychic anxiety (r = 0.01, p > 0.9), somatic anxiety (r = -0.38, p > O.l), or psychomotor retardation (r= -0.38,~ > 0. I), as measured in the HRSD. The mean blink rates for the premenopausal subgroup of 12 patients and 13 control subjects were 16/minute f 7 and 16/minute + 8 (t = 0.001, df= 24, p > 0.9), respectively. Ten SAD patients and 12 normal control subjects were studied after light therapy. The blink rates of two patients and two normal volunteers were not evaluated
Table 1. Demographic
n
and clinical characteristics
SAD patients
Control subjects
19
18
14
14
Age (yr)
38 k 7
37 + 6
HRSD
14f4
Gender
(females)
Atypical
11 f6
Blink/minute
15+8
151 1+1 15i7
of subjects
NS t = 12.2
t=
7.6
p < 0.0001 p < 0.0001 NS
Note. Values are given as mean i- SD. SAD = seasonal affective disorder. HRSD = Hamllton Rating Scale for Depressnon. Atypical = supplementary atypical symptoms charactensic of SAD.
82 after light therapy because of conditions interfering with eye-blink measurement. Logistical difficulties prevented the assessment of posttreatment blink rate in the remaining seven patients and four control subjects. SAD patients showed a significant decrease in their depression scores after light therapy: HRSD (14 + 5 vs. 7 + 8, t = 2.85, df= 9,p < 0.01) atypical symptom score (11 f 6 vs. 6 f 4, t = 2.48, df = 9, p < 0.02). No significant difference in eye-blink rate was found after light therapy for either SAD patients (13/minute + 8 vs. IO/minute f 7) or normal control subjects (15/minute * 6 vs. 14/minute f 6) (group: F = 1.32; df = I, 20; p >0.2; condition: F= 1.9; dJ’= I, 20;~ >O.l; group X condition: F= 1.8; &= I, 20; p > 0.19). Changes in blink rate were not correlated with changes in the HRSD (r = 0.17,~ > 0.6). When we analyzed the effects of light treatment on blink rates in premenopausal women (nine control subjects and five patients), we found a significant group X condition interaction (F = 7.13; df = 1, 12; Greenhouse-Geisser p < 0.03). The before- versus after-light comparison in the patient group was statistically significant (17 + 6 vs. 12 f 8, Wilcoxon’s two-sample rank test, p < 0.05).
Discussion This study demonstrated that blink rate did not differentiate SAD patients from control subjects. Because previous findings of elevated blink rate were obtained in studies of young premenopausal women (Depue et al., 1988, 1990), we also analyzed this subpopulation in an exploratory way. In this group also, blink rate did not differentiate patients from control subjects. We did not control for phase of the menstrual cycle, which might have been a confounding variable in the analysis of this subpopulation. As far as we know, however, there is no report in the literature on the variation of blink rate across the menstrual cycle, and the suggested role of estrogen in reducing dopamine activity (Joice et al., 1984) does not clearly apply to blink studies (Mackert et al., 1990). A comparison of our data on premenopausal subjects with those published by Depue et al. raises the possibility that the different conclusions in the two studies can be attributed largely to the blink rate of normal control subjects. The mean value for normal control subjects was 10 + 5 (n = 9) in the Depue et al. study versus 16 f 8 (n = 13) in our study, while the mean values for patients were, respectively, 20 + 10 (n = 17) versus 16 f 7 (n = 12). All of these mean values fall within the normal range of 7 to 24 blinks/minute described in the literature (Tecce et al., 1976; Gille et al., 1977; Karson et al., 1981a, 1990; Mackintosh et al., 1983; Stern et al., 1984). The power of our study to detect a difference in the premenopausal subjects as large as that measured by Depue et al. at the a = 0.05 level was > 0.90. It is likely, therefore, that we had an adequate sample size to detect such a difference. Consistent with the earlier finding of Depue et al. (1988), the exploratory analysis of the effect of 1 week of light therapy in the premenopausal subjects showed a decrease in blink rate following light therapy in the patients. Since our result was obtained in a small group of subjects, these data must be interpreted cautiously. A posttreatment decrease in blink rate could be attributed to habituation.
83 Such a test effect was not apparent, however, in the control group or in the patients who were not premenopausal. Previous drug treatment could also be invoked to explain changes in blink rate. The eye-blink rate-thought to be connected to the dopamine system-is reduced by neuroleptics (Karson, 1983) while antidepressants have been reported either to increase (Karson, 1979) or decrease (Mackintosh et al., 1983) blink rate. Chronic use of neuroleptics could also produce profound changes in the dopamine system, leading to variations in blink rate secondary to the long-term effects of the drug (Stevens, 1978a, 19783). From this perspective, our results are unlikely to be a confounding effect of previous drug treatment. Most winter SAD patients are drugfree during the months preceding the winter onset of depression, and they are rarely treated with neuroleptics. The particular effects of light therapy on blink rate in the premenopausal subgroup are noteworthy in light of a trend found in a therapeutic trial of levodopa for winter SAD. In that study, we have identified a favorable trend toward clinical response only in premenopausal women (Oren et al., 1991). The effect of light therapy on blink rate and the results of the levodopa treatment study suggest that premenopausal SAD may distinctly reflect involvement of dopamine systems. In view of the exploratory nature of the data obtained in this study, a complex attempt to explain how light may influence the systems involved in the regulation of blink rate does not appear warranted. A possible working hypothesis is that light therapy in premenopausal winter SAD patients interacts with the blink alpha neurocircuit (BANC) theorized by Karson et al. (1990). According to this model, light therapy might stimulate the activity of structures (e.g., reticular formation, occipital cortex) that inhibit the blink rate. In conclusion, the present study does not support the idea that an elevated blink rate is a general biological marker in SAD. The decreased blink rate observed after light therapy in premenopausal patients suggests that biological systems regulating blink rate may be involved in the mechanisms of action of light in this subgroup of patients. Further examination of the biological and neurophysiological aspects of premenopausal winter SAD patients may clarify whether this group could be characterized as a biologically distinct subtype of the condition. References Arbisi, P.A.; Depue, R.A.; Spoont, M.R.; Leon, A.; and Ainsworth, B. Thermoregulatory response to thermal challenge in seasonal affective disorder: A preliminary report. Psychiatry Research, 28:323-334, 1989. Bartko, G.; Herczeg, I.; and Zador, G. Blink rate response to haloperidol as a possible predictor of therapeutic outcome. Biological Psychiatry. 27:113-l 15, 1990. Beninger, R.J. The role of dopamine in locomotor activity and learning. Brain Research Review, 6:173-196, 1983. Depue, R.A.; Arbisi, P.; Krauss, S.; Iacono, W.C.; Leon, A.; Muir, R.; and Allen, J. Seasonal independence of low prolactin concentration and high spontaneous eye blink rates in unipolar and bipolar II seasonal affective disorder. Archives of General Psychiatry, 47:356364, 1990.
84
Depue, R.A.; Arbisi, P.; Spoont, M.R.; Krauss. S.; Leon, A.; and Ainsworth, B. Seasonal and mood independence of low basal prolactin secretion in premenopausal women with seasonal affective disorder. American Journal of Psychiatry, 146:989-995, 1989. Depue, R.A., and lacono, W.G. Neurobehavioral aspects of affective disorders. Annual Review
qf Psychology,
40~457-492,
1989.
Depue, R.A.; Iacono, W.G.; Muir, R.; and Arbisi. P. Effect spontaneous eye blink rate in subjects with seasonal affective disorder. Ps.vchiatry,
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Doane. M.G. Interaction of eyelids and tears in cornea1 wetting and dynamics of the normal human eye blink. American Journal of’Ophthalmology, 89:507-516, 1980. Gille, H.G. von; Otto, 0.; and Ullsperger, P. Aktivierungs-Abhangigkeit, Anforderunsspecifitat und Zeitverhalten Physiologischer und Psychologische Variablen bei gestuften Leistungsanforderungen im Rhamen des Konzentrationleistung-Tests. Zeitschrift ./;ir Psychologie,
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Hall, A. The origin and purposes 461,
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Karson, C.N.; Freed. W.J.; Kleinman, J.E.; Bigelow. L.B.; and Wyatt, R.J. Neuroleptics decrease blinking in schizophrenic subjects. Biological Ps,vchiatr_v. 16:679-682, 198lh. Kleinman. J.E.; Karson, C.N.; Weinberger, D.R.; Freed, W.J.; Berman, K.F.; and Wyatt, R.J. Eye-blinking and cerebral ventricular size in chronic schizophrenic patients. American Journal
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Mackert, A.; Woyth, C.; Malte-Flechtner, K.; and Volz, H.P. Increased blink rate in drug-naive acute schizophrenic patients. Biological Psychiatry, 21: I 197-i 202, 1990. Mackintosh, J.H.; Kumar, R.; and Kitamura, T. Blink rate in psychiatric illness. British Journal
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Rosenthal, N.E., and Heffernan, M.M. Bulimia, carbohydrate craving, and depression: A central connection. In: Wurtman, R.J., and Wurtman, J.J., eds. Nutrition andrhe Bruin. New York: Raven Press, 1986. pp. 139-166. Rosenthal, N.E.; Sack, D.A.; Gillin, J.C.; Lewy, A.J.; Goodwin, F.K.; Davenport, Y.; Mueller, P.S.; Newsome. D.A.; and Wehr, T.A. Seasonal affective disorder: A description of the syndrome and preliminary findings with light therapy. Archives qf General Ps~vchiatr.t,, 4 I :72-80, 1984. Spitzer, R.L., and Williams, J.B.W. Structured ClinicalIntervie~+~for DSM-III-R--Patient Version. (SCID-P, S/ 1186) New York: New York State Psychiatric Institute, 1986. Stern, J.A.; Walrath, L.C.; and Goldstein, R. The endogenous eyeblink. Ps~v~hoph?,sio/og_,, 21:22-33, 1984. Stevens, J.R. Disturbances of ocular movements and blinking in schizophrenia. Journal of Neurolog_v, Neurosurgerv, and Psychiatry, 4 I : i 024- 1030, I978a. Stevens, J.R. Eye blink and schizophrenia: Psychosis or tardive dyskinesia? American Journal qf Psychiatry, 135:223-226, 19786. Tecce, J.J.; Savignano-Bowman, J.; and Meinbresse, D. Contingent negative variation and the distraction-arousal hypothesis. Electroencephalographl: and Clinical Neurophysiology, 41:277-286, 1976. Terman, M.; Williams, J.M.; and Terman, J.S. Light therapy for winter depression: A clinician’s guide. In: Keller P.A., ed. Innovations in Clinical Practice: A Source Book. Sarasota, FL: Professional Resource Exchange, 199 I. pp. 179-22 I.
Spontaneous Disorder
79
Eye Blink Rate in Winter Seasonal Affective
Giuseppe Barbato, Douglas and Dan A. Oren
E. Moul, Paul Schwartz,
Norman
E. Rosenthal,
Received June 24, 1992; revised version received January 12, 1993; accepted January 26, 1993.
Abstract. We investigated spontaneous eye-blink rates in 19 drug-free patients with winter seasonal affective disorder (SAD) and 18 normal control subjects. At baseline, there were no significant differences between the two groups (mean + SD blink rate: lS/minute * 8 vs. IS/minute + 7). Light therapy (10,000 lux: I hour each morning for 1 week) produced no significant change in mean (4 SD) blink rates either in 10 SAD patients (13/minute + 8 vs. IO/minute f 7) or in 12 normal control subjects (15/minute f 6 vs. 14/minute + 6). A post hoc exploratory analysis of the effect of light therapy on premenopausal female subjects (5 patients and 9 control subjects) showed a significant decrease in mean (& SD) blink rate in the patients after treatment (17 + 6 vs. 12 f 8 compared with 15 5 7 vs. 16 + 5). These results do not support the idea that an elevated blink rate may be a general biological marker in SAD, but they suggest a possible link between light treatment and mechanisms that regulate blink rate in premenopausal SAD patients. Key Words.
Depression,
light
therapy,
circannual
rhythms,
treatment,
sex
differences.
Spontaneous
eye blinks
less than one-half stimuli (Karson,
are defined
second,
that
as bilateral
occur
brief eye closures,
continually
and
in the
which absence
usually
last
of external
1983). The frequency-normally IO-20 blinks/ minute-is not related to immediate physiological needs of the ocular system, since only two to four blinks every minute are necessary to prevent cornea1 drying (Norn, 1969; Doane, 1980). Several studies suggest that blink rate is associated with central dopaminergic function. Blink rate is decreased in Parkinson’s disease (Hall, 1945; Karson, 1983) a disorder of dopamine deficiency, while it is increased in schizophrenia (Stevens, 1978~; Karson et al., 19816; Mackert et al., 1990) a disorder in which increased dopaminergic function is hypothesized. Blink rate is also increased in levodopainduced dyskinesia and decreased by neuroleptic treatment (Karson, 1983; Kleinman et al., 1984; Bartko et al., 1990; Mackert et al., 1990).
Giuseppe Barbato,
M.D., is Visiting Fellow; Norman E. Rosenthal, Environmental Psychiatry; Douglas E. Maul, M.D., Paul Schwartz, M.D., Senior Clinical Investigators, Clinical Psychobiology Branch, National Bethesda, MD. (Reprint requests to Dr. D.A. Oren, Clinical Psychobiology Mental Health, Bldg. 10, Rm. 4S-239, Bethesda, MD 20892, USA.) 0165-1781/93/$06.00
@ 1993 Elsevier Scientific
Publishers
Ireland
Ltd
M.D., is Chief. Section on and Dan A. Oren, M.D., are Institute of Mental Health, Branch, National lnstitute of
80 Recently, Depue et al. (1988) reported an increased eye-blink rate in four premenopausal women with winter seasonal affective disorder (SAD) compared with four premenopausal control subjects. Light therapy normalized the elevated blink rate. These data suggest that an elevated blink rate may be a state marker in SAD. Depue et al. (1990) extended their sample to a total of 17 premenopausal patients and 11 premenopausal control subjects, and confirmed the increase of blink rate in SAD patients. Paradoxically, 11 patients who were also studied during summer remissions showed no significant difference in blink rate between winter and summer, thereby suggesting that blink rate is a trait marker in SAD. Depue et al. (1990) proposed that the elevated blink rate might result from a compensatory up-regulation of dopamine D, receptors involved in the eye-blink system secondary to reduced functional activity of dopamine. The clinical and biological features of winter SAD support the hypothesis that dopaminergic systems may be disturbed in the disorder. SAD symptoms include psychomotor retardation and loss of energy, both of which could be behavioral manifestations of dopaminergic deficiency (Beninger, 1983; Depue and Iacono, 1989). Depue et al. (1989) found lower prolactin levels in SAD, and Arbisi et al. (1989) reported diminished responses to thermoregulatory challenges in SAD-both of which may be expressions of dopaminergic alterations in winter SAD. The present study was designed to analyze the blink rate and the effect of light therapy in a larger and more varied sample of winter SAD patients and control subjects than has been studied previously, with the aim of better assessing to what extent this abnormality may be a general feature of the condition and a possible clue to disturbed dopaminergic functioning.
Methods The study was conducted between November II, 1990, and March 13, 1991. Nineteen winter SAD patients (5 men, 14 women; mean age = 38 years, SD = 7) and IS normal control subjects (4 men, 14 women; mean age = 37 years, SD = 6) were recruited through advertisements and referrals. The patients had a winter depression history of 15 (SD = IO) years. Eighteen out of 19 patients had individually age- and sex-matched controls. All subjects were evaluated with the Structured Clinical Interview for DSM-III-R(SCID-R; Spitzer and Williams, 1986). Diagnosis of winter SAD was established on the basis of the criteria of Rosenthal et al. (1984). Of the 19 patients in our study, I I had no history of any previous psychotropic drug treatment and only two had received an antidepressant medication in the 7 months before the study. All subjects had been drug-free for at least 2 weeks before entering the study and remained drug-free for the duration of the study. No subject had received fluoxetine in the 6 weeks before the study. Patients had no concurrent Axis 1 psychiatric illness. Control subjects had no history of Axis 1 psychiatric illness. All subjects had normal physical examinations and routine laboratory screening before testing and had no significant medical, neurological, or ophthalmological illness. Subjects who were wearing contact lenses or who were suffering at the time of testing from a cold, flu, headache, or any condition interfering with visual sensitivity to light were excluded. All subjects gave informed consent. The two groups were studied before and after I week of 10,000 lux light treatment administered by having the subject sit I foot from a light source (Sunbox@) for I hour each morning. On the days of eye-blink testing, the Structured Interview Guide for the HamiltonSeasonal Affective Disorder version (SIGH-SAD; Terman et al., 1991) was used in the assessment of the severity of depressive symptoms by a rater who had no knowledge of
81 treatment condition. The SIGH-SAD incorporates the Hamilton Rating Scale for Depression (HRSD) and the supplementary atypical symptoms characteristic of SAD (Rosenthal and Heffernan, 1986). At the time of study entry, the patients had been clinically depressed for a mean of 6 (SD = 2) weeks. Vertical and horizontal electro-oculograms (EOGs) were recorded on a Grass 78-D polygraph. Gold skin electrodes were placed 3.0 cm above and 2.0 cm below the left eye as measured from the center of the pupil to the center of the electrode (vertical EOG), and at the outer canthi (horizontal EOG). An eye blink was defined as a sharp high amplitude wave > 100 PV and < 400 msec in duration (Depue et al., 1988, 1990). Polygraphic records were obtained between 2 p.m. and 5 p.m. in an air-conditioned room with indoor light of 150 lux at the level of the subject’s eyes. Each subject had 10 minutes to become adjusted to the recording room and light environment. During the recording, each subject sat silently in front of a blank, neutral wall. The subject was asked to remain awake, so that we could study basal ocular activity. No subject fell asleep during the recording session. Eye-blink rate was taken as the mean number of blinks that occurred during the first 2 consecutive minutes after a 5-minute accommodation period. Subjects were unaware of the accommodation period. Comparisons before treatment were made with unpaired f tests. Analysis of variance (ANOVA) with patients vs. subjects as a grouping factor and before vs. after light therapy as a repeated measure was used to study blink rates of those who completed the course of phototherapy. Correlations between blink rate and degree of clinical symptomatology were determined using the Pearson coefficient correlation (r). To focus on a group similar to that studied by Depue et al. (1988) a post hoc analysis of data was performed on premenopausal women (12 patients and 13 controls). Results are presented as mean + SD.
Results Before light treatment, the mean eye-blink rates for the winter SAD patients (n = 19) and control subjects (n = 18) were (Table 1) 15/minute f 8 and IS/minute + 7 (t = 0.23, df = 35, p > 0.9) respectively. SAD patients showed no significant correlations between eye-blink rates and the severity of depression, either when the 21-item HRSD score (r = 0.22, p > 0.4) or the atypical symptom score (r = 0.15, p > 0.5) was considered. Eye-blink rate was not significantly correlated with psychic anxiety (r = 0.01, p > 0.9), somatic anxiety (r = -0.38, p > O.l), or psychomotor retardation (r= -0.38,~ > 0. I), as measured in the HRSD. The mean blink rates for the premenopausal subgroup of 12 patients and 13 control subjects were 16/minute f 7 and 16/minute + 8 (t = 0.001, df= 24, p > 0.9), respectively. Ten SAD patients and 12 normal control subjects were studied after light therapy. The blink rates of two patients and two normal volunteers were not evaluated
Table 1. Demographic
n
and clinical characteristics
SAD patients
Control subjects
19
18
14
14
Age (yr)
38 k 7
37 + 6
HRSD
14f4
Gender
(females)
Atypical
11 f6
Blink/minute
15+8
151 1+1 15i7
of subjects
NS t = 12.2
t=
7.6
p < 0.0001 p < 0.0001 NS
Note. Values are given as mean i- SD. SAD = seasonal affective disorder. HRSD = Hamllton Rating Scale for Depressnon. Atypical = supplementary atypical symptoms charactensic of SAD.
82 after light therapy because of conditions interfering with eye-blink measurement. Logistical difficulties prevented the assessment of posttreatment blink rate in the remaining seven patients and four control subjects. SAD patients showed a significant decrease in their depression scores after light therapy: HRSD (14 + 5 vs. 7 + 8, t = 2.85, df= 9,p < 0.01) atypical symptom score (11 f 6 vs. 6 f 4, t = 2.48, df = 9, p < 0.02). No significant difference in eye-blink rate was found after light therapy for either SAD patients (13/minute + 8 vs. IO/minute f 7) or normal control subjects (15/minute * 6 vs. 14/minute f 6) (group: F = 1.32; df = I, 20; p >0.2; condition: F= 1.9; dJ’= I, 20;~ >O.l; group X condition: F= 1.8; &= I, 20; p > 0.19). Changes in blink rate were not correlated with changes in the HRSD (r = 0.17,~ > 0.6). When we analyzed the effects of light treatment on blink rates in premenopausal women (nine control subjects and five patients), we found a significant group X condition interaction (F = 7.13; df = 1, 12; Greenhouse-Geisser p < 0.03). The before- versus after-light comparison in the patient group was statistically significant (17 + 6 vs. 12 f 8, Wilcoxon’s two-sample rank test, p < 0.05).
Discussion This study demonstrated that blink rate did not differentiate SAD patients from control subjects. Because previous findings of elevated blink rate were obtained in studies of young premenopausal women (Depue et al., 1988, 1990), we also analyzed this subpopulation in an exploratory way. In this group also, blink rate did not differentiate patients from control subjects. We did not control for phase of the menstrual cycle, which might have been a confounding variable in the analysis of this subpopulation. As far as we know, however, there is no report in the literature on the variation of blink rate across the menstrual cycle, and the suggested role of estrogen in reducing dopamine activity (Joice et al., 1984) does not clearly apply to blink studies (Mackert et al., 1990). A comparison of our data on premenopausal subjects with those published by Depue et al. raises the possibility that the different conclusions in the two studies can be attributed largely to the blink rate of normal control subjects. The mean value for normal control subjects was 10 + 5 (n = 9) in the Depue et al. study versus 16 f 8 (n = 13) in our study, while the mean values for patients were, respectively, 20 + 10 (n = 17) versus 16 f 7 (n = 12). All of these mean values fall within the normal range of 7 to 24 blinks/minute described in the literature (Tecce et al., 1976; Gille et al., 1977; Karson et al., 1981a, 1990; Mackintosh et al., 1983; Stern et al., 1984). The power of our study to detect a difference in the premenopausal subjects as large as that measured by Depue et al. at the a = 0.05 level was > 0.90. It is likely, therefore, that we had an adequate sample size to detect such a difference. Consistent with the earlier finding of Depue et al. (1988), the exploratory analysis of the effect of 1 week of light therapy in the premenopausal subjects showed a decrease in blink rate following light therapy in the patients. Since our result was obtained in a small group of subjects, these data must be interpreted cautiously. A posttreatment decrease in blink rate could be attributed to habituation.
83 Such a test effect was not apparent, however, in the control group or in the patients who were not premenopausal. Previous drug treatment could also be invoked to explain changes in blink rate. The eye-blink rate-thought to be connected to the dopamine system-is reduced by neuroleptics (Karson, 1983) while antidepressants have been reported either to increase (Karson, 1979) or decrease (Mackintosh et al., 1983) blink rate. Chronic use of neuroleptics could also produce profound changes in the dopamine system, leading to variations in blink rate secondary to the long-term effects of the drug (Stevens, 1978a, 19783). From this perspective, our results are unlikely to be a confounding effect of previous drug treatment. Most winter SAD patients are drugfree during the months preceding the winter onset of depression, and they are rarely treated with neuroleptics. The particular effects of light therapy on blink rate in the premenopausal subgroup are noteworthy in light of a trend found in a therapeutic trial of levodopa for winter SAD. In that study, we have identified a favorable trend toward clinical response only in premenopausal women (Oren et al., 1991). The effect of light therapy on blink rate and the results of the levodopa treatment study suggest that premenopausal SAD may distinctly reflect involvement of dopamine systems. In view of the exploratory nature of the data obtained in this study, a complex attempt to explain how light may influence the systems involved in the regulation of blink rate does not appear warranted. A possible working hypothesis is that light therapy in premenopausal winter SAD patients interacts with the blink alpha neurocircuit (BANC) theorized by Karson et al. (1990). According to this model, light therapy might stimulate the activity of structures (e.g., reticular formation, occipital cortex) that inhibit the blink rate. In conclusion, the present study does not support the idea that an elevated blink rate is a general biological marker in SAD. The decreased blink rate observed after light therapy in premenopausal patients suggests that biological systems regulating blink rate may be involved in the mechanisms of action of light in this subgroup of patients. Further examination of the biological and neurophysiological aspects of premenopausal winter SAD patients may clarify whether this group could be characterized as a biologically distinct subtype of the condition. References Arbisi, P.A.; Depue, R.A.; Spoont, M.R.; Leon, A.; and Ainsworth, B. Thermoregulatory response to thermal challenge in seasonal affective disorder: A preliminary report. Psychiatry Research, 28:323-334, 1989. Bartko, G.; Herczeg, I.; and Zador, G. Blink rate response to haloperidol as a possible predictor of therapeutic outcome. Biological Psychiatry. 27:113-l 15, 1990. Beninger, R.J. The role of dopamine in locomotor activity and learning. Brain Research Review, 6:173-196, 1983. Depue, R.A.; Arbisi, P.; Krauss, S.; Iacono, W.C.; Leon, A.; Muir, R.; and Allen, J. Seasonal independence of low prolactin concentration and high spontaneous eye blink rates in unipolar and bipolar II seasonal affective disorder. Archives of General Psychiatry, 47:356364, 1990.
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