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Gender differences in glycosylated hemoglobin levels in seasonal affective disorder patients and controls
Gender Differences in Glycosylated Hemoglobin Levels in Seasonal Affective Disorder Patients and Controls Isaac M. Neuhaus, Paul J. Schwartz, Erick H. Turner, Susana Feldman-Naim, Jeffery R. Matthews, Gregory Lam, and Norman E. Rosenthal Seasonal affective disorder (SAD) has been shown to manifest different symptoms in female and male patients. Specifically, women with SAD have been shown to have greater increases in overeating, weight gain, and increased sleep as compared with their male counterparts. Given these dietary changes, we predicted that female SAO patients would exhibit increased glycosylated hemoglobin (HbA1) levels, indicative of chronically elevated glucose levels. Twentyt w o p a t i e n t s (15 women and seven men) and matched controls were enrolled during the winter season and tested for HbA1 levels. A three-way analysis of variance (ANOVA; gender x group x season) was insignifi-
cant and the result was a negative study. After the initial hypothesis was rejected, we undertook a posthoc analysis of the data, from which emerged that in winter, women patients had higher HbA1 levels as compared with matched controls. As our original hypothesis was rejected, we cannot accept the results of the post-hoc study. However, numerous other studies have demonstrated that female and male SAD patients differ in their pathophysiology, and are suggestive that in future analyses ought to consider analyzing subjects separately across gender.
EASONAL AFFECTIVE DISORDER (SAD) is a mood disorder characterized by recurrent winter depressive episodes, with remission or hypomanic periods in the spring and summer. The depressions are associated with vegetative symptoms such as overeating, carbohydrate craving, weight gain, and increased sleep.l The prevalence of SAD is greater in premenopausal women compared with men. 2 In addition, the characteristic atypical symptoms of SAD have been shown to manifest gender differences. Women with SAD tend to report greater increases in overeating, weight gain, and sleep in comparison to men with SAD. 3 However, these differences are not exclusive to SAD, as non-seasonally 4-7 depressed women and women in general 8 have also reported increased appetite, weight gain, and carbohydrate craving as compared with their male counterparts. Dietary and weight changes such as those reported to occur in winter have been associated with a reduction in insulin sensitivity, resulting in a decrease of glucose uptake by the ceils and an increase of blood insulin levels. 9 Abnormalities in glucose and insulin functioning are characteristic of non-insulin-dependent diabetes mellitus
(NIDDM), in which insulin resistance results in elevated insulin and glucose levels. The response to a glucose tolerance test in untreated SAD patients 1° resembles the response found in NIDDM, namely, increased glucose and insulin levels following glucose intake, albeit to a less marked degree. In patients with NIDDM, glycosylated hemoglobin levels are routinely measured to monitor longterm blood glucose levels. The irreversible binding of glucose to hemoglobin varies in relation to the glucose concentration over the life span of the red blood cell. Thus, glycosylated hemoglobin concentrations reflect blood glucose levels over the preceding 8-week period, and are not affected by shortterm variations in factors such as food intake, stress, and other variables. 11Glycosylated hemoglobin levels have been shown to vary seasonally in diabetic patients, with a peak in the winter.12,]3 Given the reported SAD gender differences in weight gain and dietary intake, in addition to the documented differences in the response to a glucose tolerance test in SAD patients, we hypothesized that women with SAD would have chronically elevated blood glucose levels and increased insulin insensitivity during the winter. We further hypothesized that the differences in blood glucose levels and insulin insensitivity between female SAD patients and controls would show the most marked changes during the winter months, given that this is the time in which the greatest changes in carbohydrate craving and weight gain occur. To test these hypotheses, we measured glycosylated hemoglobin (HbAI) levels in female and male SAD
S
From the Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD. Address reprint requests to Norman E. Rosenthal, M.D., Clinical Psychobiology Branch, National Institute of Mental Health, Bldg 10, Room 4S-239, 10 Center Dr, Bethesda, MD 20892-1390. Copyright © 1999 by W.B. Saunders Company 0010-440X/99/4003-0003510.00/0
234
Copyright© 1999by W.B. Saunders Company
ComprehensivePsychiatry,Vol. 40, No. 3 (May/June), 1999: pp 234-237
GLYCOSYLATED HEMOGLOBIN A N D CONTROLS IN SAD
patients and matched controls in winter and again in summer. To our knowledge, this is the first report describing the m e a s u r e m e n t of HbA~ in depressed patients.
METHOD
235
Table 2. HbA1 Levels (%) by Season (mean _+ SD) Group
Winter
Summer
SAD
5.8 + .8
5.9 ± .6
Control
5.3 -+ .8
5.8 ± .5
Women
Men
Subjects Twenty-two patients (15 women and seven men) met the following inclusion criteria: (1) the diagnostic criteria for SAD of Rosenthal et all; (2) a score of at least 15 on the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version14 (SIGH-SAD); (3) absence of any additional current axis I disorders; (4) good physical health as determined by physical examination and routine blood tests; and (5) no use of light therapy for the current winter depression. All subjects provided informed consent for participation in the study. Twenty-two healthy controls were matched with the patients on the basis of age, gender, and body mass index ([BMI] kg/m2), and menstrual and contraceptive status for the women. Controls were required to have no personal or family history of an axis I psychiatric disorder and to be physically healthy. Both female and male SAD patients showed no significant differences compared with the controls for age and BMI (Table l). Care was taken to ensure that the patients and controls did not differ in terms of BMI and age, as both of these factors could contribute to differences in HbAI levels.
Study Design Both patients and controls participated in the study during the same winter season. Nineteen patients (13 women and six men)
and 19 controls (12 women and seven men) participated again in the summer. Subjects provided a morning blood sample at the Clinical Center of the National Institutes of Health, which analyzed the HbA] levels at the Clinical Center Laboratory using gel electrophoresis. Participants also received a mood rating on the day before the blood sample was obtained.
Statistics We compared HbA] levels in patients and controls by analysis of variance (ANOVA) with two grouping measures (gender and diagnostic group) and one repeated measure (season).
SAD
6.4 ÷ 1,8
5.9 -+ .6
Control
6.0 ± .6
6.2 ± .8
A N O V A (gender X group X season). A m a i n effect for gender was observed (F = 3.18, P < .03), with m e n having higher H b A 1 levels than w o m e n . The B M I correlated with the HbA1 level (r = .51, P < .05). W i t h i n the patient group for both w o m e n and men, there was no significant correlation b e t w e e n HbA] and the degree of depression at the time of blood sampling, as m e a s u r e d by typical or atypical symptoms. Additionally, there was no relationship b e t w e e n the reported degree of carbohydrate craving or weight gain and the S I G H - S A D and HbA~. M e n and w o m e n showed no differences in the self-report of carbohydrate craving, weight gain, and increased appetite. Because we had an a priori prediction that w o m e n with S A D might exhibit higher HbA] levels in winter, we also performed a post hoc two-way A N O V A on w o m e n across the seasons and a group t test on w o m e n in winter. There was no significant group by season effect w h e n w o m e n alone were considered. However, on the group t test, w o m e n with S A D were found to have increased HbA~ c o m p a r e d with c o n t r o l s ( 5 . 2 5 % _+ 0.75% v 5.83% ___ 0.74%, t = 2.14, df = 28, P < .05).
DISCUSSION RESULTS HbA1 levels (mean _+ SD) are reported in Table 2. N o interaction was found in a three-way
Table 1. Subject Characteristics (mean _+ SD) Group
SIGH-SAD Score
Age (yr)
BMI (kg/m 2)
25.3 + 5.3
39.7 ± 9.7
27.2 ± 9.5
38.3 + 9.5
25.4 ± 5.3
Women SAD Control Men SAD Control
24.6 ± 6.4
39.7 _+ 9.0
29.2 ± 4.6
44.6 + 8.8
28.4 ± 4.9
G i v e n that the three-way A N O V A (gender x group X season) was negative, we are u n a b l e to support our predicted hypothesis that female S A D patients have elevated HbA~ levels and therefore a b n o r m a l glucose regulation during the winter. Nevertheless, we r e c o g n i z e that the n e g a t i v e A N O V A m a y be a function of insufficient statistical power. A power analysis demonstrated that a sample size of greater than 300 patients would be needed to show a significant effect. Additionally, one must question whether such a difference, while statistically significant, would be biologically relevant. Even if, on replication, w o m e n are found to
236
NEUHAUS ET AL
have higher HbA~ levels than men, the weak effect size suggests that any disturbances in carbohydrate metabolism in SAD are probably not of major clinical significance. As such, we are forced to reject our hypothesis. However, when examined in one specific way, namely a group t test that examined women alone in winter, female SAD patients did appear to have elevated HbA1 levels compared with a group of matched controls. Nevertheless, such a statistical approach is relatively weak, and the finding would need to be replicated before it could be confidently accepted. One possible shortcoming of this study is the fact that we did not specifically measure the variable fraction, HbAlc. Since HbAlc constitutes 60% to 80% of HbA1, any variation in HbA~c is reflected in HbAI levels. As a result, HbA~ is used extensively for the clinical purpose of monitoring diabetic control. However, it is possible that the nonvariable fraction of HbA1 obscured any variation in glycosylated hemoglobin levels. As such, it would be of interest to measure HbAlc in future studies, since a
variation in this component accounts for most of the variation in HbA1 as a whole. For inclusion in the study, it was required that patients meet criteria for winter depression at the time of participation, but not for the full 8 weeks prior. As HbA1 levels are reflective of glucose control for the previous 1 to 3 months, if patients were not depressed for much of this period, it may have contributed to the negative results. While the predicted hypothesis was rejected in the present study, other studies have found gender differences in SAD patients. Intrinsic melatonin secretion in response to the lengthening winter night differed between SAD women and men. 15 In SAD patients, plasma prolactin levels, ~6-~8electroretinographic b-wave amplitudes, 19 and changes in the eye blink rate in response to light therapy2° also showed gender differences. These findings support the concept that SAD manifests different pathophysiological changes in women and men. It would thus appear that in future studies of SAD patients, separate analyses according to gender are warranted.
REFERENCES 1. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Wehr TA. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 1984;41:72-80. 2. Kasper S, Wehr TA, Bartko JJ, Gaist PA, Rosenthal NE. Epidemiological findings of seasonal changes in mood and behavior: a telephone survey of Montgomery County, Maryland. Arch Gen Psychiatry 1989;46:823-833. 3. Leibenhift E, Hardin TA, Rosenthal NE. Gender differences in seasonal affective disorder. Depression 1995;3:13-19. 4. Ernst C, Angst J. The Zurich Study XII. Sex differences in depression: evidence from longitudinal epidemiological data. Eur Arch Psychiatry Clin Neurosci 1992;241:222-230. 5. Young MA, Scheftner WA, Fawcett J, Klermann GL. Gender differences in the clinical features of unipolar major depressive disorder. J Nerv Ment Dis 1990;178:200-203. 6. Frank E, Carpenter LL, Kupfer DJ. Sex differences in recurrent depression: are there any that are significant? Am J Psychiatry 1988;145:41-45. 7. Angst J, Dobler-Mikola A. Do the diagnostic criteria determine the sex ratio of depression? J Affect Disord 1984;7: 189-198. 8. Rosen LN, Rosenthal NE. Seasonal variations in mood and behavior in the general population: a factor analytic approach. Psychiatry Res 1991;38:271-283. 9. Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med 1993;119:655-660.
10. Krauchi K, Keller U, Leonhardt G, Haug HJ, Brunner DP, Hetsch C, et al. Depressed SAD patients exhibit impaired insulin-glucose homeostasis and altered palatability of sucrose in winter. Abstract presented at the Sixth Annual Meeting of the Society for Light Treatment and Biological Rhythms; June 23-24, 1994; Bethesda, MD. 11. Nathan DM, Singer DE, Hurzthal K, Goodson JD. The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 1984;310:341-346. 12. Hinde FR, Standen PJ, Mann NP, Johnston DI. Seasonal variation of hemoglobin A1 in children with insulin-dependent diabetes mellitus. Eur J Pediatr 1989;148:597-599. 13. Ferrie CD, Sharpe TC, Price DA, Surtees RA. Seasonal variation of glycosylated hemoglobin. Arch Dis Child 1987;62: 959-960. 14. Williams JBW, Link MJ, Rosenthal NE, Amira L, Terman M. Structured Interview Guide for the Hamilton Depression Rating Scale: Seasonal Affective Disorder Version. New York, NY: New York State Psychiatric Institute, 1992. 15. Wehr TA. Melatonin and seasonal rhythms. J Biol Rythms 1997;12:517-526. 16. Oren DA, Levendosky AA, Kasper S, Duncan CC, Rosenthal NE. Circadian profiles of cortisol, prolactin and thyrotropin in seasonal affective disorder. Biol Psychiatry 1996;39:157-170. 17. Depue RA, Arbisi P, Krauss S, Iacono WG, Leon A, Muir R, et al. Seasonal independence of low prolactin concentration and high spontaneous eye blink rates in unipolar and bipolar II
GLYCOSYLATED HEMOGLOBIN AND CONTROLS IN SAD
seasonal affective disorder. Arch Gen Psychiatry 1990;47:356364. 18. Arbisi PA, Depue RA, Spoont MR, Leon A, Ainswith B. Thermoregulatory response to thermal challenge in seasonal affective disorder: a preliminary report. Psychiatry Res 1993;28: 323-334.
237
19. Lam RW, Beattie CW, Buchanan A, Mador JA. Electroretinography in seasonal affective disorder. Psychiatry Res 1992;43:55-63. 20. Barbato G, Moul DE, Schwartz PJ, Rosenthal NE, Oren DA. Spontaneous eye-blink rate in winter seasonal affective disorder. Psychiatry Res 1993;47:79-85.
cant and the result was a negative study. After the initial hypothesis was rejected, we undertook a posthoc analysis of the data, from which emerged that in winter, women patients had higher HbA1 levels as compared with matched controls. As our original hypothesis was rejected, we cannot accept the results of the post-hoc study. However, numerous other studies have demonstrated that female and male SAD patients differ in their pathophysiology, and are suggestive that in future analyses ought to consider analyzing subjects separately across gender.
EASONAL AFFECTIVE DISORDER (SAD) is a mood disorder characterized by recurrent winter depressive episodes, with remission or hypomanic periods in the spring and summer. The depressions are associated with vegetative symptoms such as overeating, carbohydrate craving, weight gain, and increased sleep.l The prevalence of SAD is greater in premenopausal women compared with men. 2 In addition, the characteristic atypical symptoms of SAD have been shown to manifest gender differences. Women with SAD tend to report greater increases in overeating, weight gain, and sleep in comparison to men with SAD. 3 However, these differences are not exclusive to SAD, as non-seasonally 4-7 depressed women and women in general 8 have also reported increased appetite, weight gain, and carbohydrate craving as compared with their male counterparts. Dietary and weight changes such as those reported to occur in winter have been associated with a reduction in insulin sensitivity, resulting in a decrease of glucose uptake by the ceils and an increase of blood insulin levels. 9 Abnormalities in glucose and insulin functioning are characteristic of non-insulin-dependent diabetes mellitus
(NIDDM), in which insulin resistance results in elevated insulin and glucose levels. The response to a glucose tolerance test in untreated SAD patients 1° resembles the response found in NIDDM, namely, increased glucose and insulin levels following glucose intake, albeit to a less marked degree. In patients with NIDDM, glycosylated hemoglobin levels are routinely measured to monitor longterm blood glucose levels. The irreversible binding of glucose to hemoglobin varies in relation to the glucose concentration over the life span of the red blood cell. Thus, glycosylated hemoglobin concentrations reflect blood glucose levels over the preceding 8-week period, and are not affected by shortterm variations in factors such as food intake, stress, and other variables. 11Glycosylated hemoglobin levels have been shown to vary seasonally in diabetic patients, with a peak in the winter.12,]3 Given the reported SAD gender differences in weight gain and dietary intake, in addition to the documented differences in the response to a glucose tolerance test in SAD patients, we hypothesized that women with SAD would have chronically elevated blood glucose levels and increased insulin insensitivity during the winter. We further hypothesized that the differences in blood glucose levels and insulin insensitivity between female SAD patients and controls would show the most marked changes during the winter months, given that this is the time in which the greatest changes in carbohydrate craving and weight gain occur. To test these hypotheses, we measured glycosylated hemoglobin (HbAI) levels in female and male SAD
S
From the Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD. Address reprint requests to Norman E. Rosenthal, M.D., Clinical Psychobiology Branch, National Institute of Mental Health, Bldg 10, Room 4S-239, 10 Center Dr, Bethesda, MD 20892-1390. Copyright © 1999 by W.B. Saunders Company 0010-440X/99/4003-0003510.00/0
234
Copyright© 1999by W.B. Saunders Company
ComprehensivePsychiatry,Vol. 40, No. 3 (May/June), 1999: pp 234-237
GLYCOSYLATED HEMOGLOBIN A N D CONTROLS IN SAD
patients and matched controls in winter and again in summer. To our knowledge, this is the first report describing the m e a s u r e m e n t of HbA~ in depressed patients.
METHOD
235
Table 2. HbA1 Levels (%) by Season (mean _+ SD) Group
Winter
Summer
SAD
5.8 + .8
5.9 ± .6
Control
5.3 -+ .8
5.8 ± .5
Women
Men
Subjects Twenty-two patients (15 women and seven men) met the following inclusion criteria: (1) the diagnostic criteria for SAD of Rosenthal et all; (2) a score of at least 15 on the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version14 (SIGH-SAD); (3) absence of any additional current axis I disorders; (4) good physical health as determined by physical examination and routine blood tests; and (5) no use of light therapy for the current winter depression. All subjects provided informed consent for participation in the study. Twenty-two healthy controls were matched with the patients on the basis of age, gender, and body mass index ([BMI] kg/m2), and menstrual and contraceptive status for the women. Controls were required to have no personal or family history of an axis I psychiatric disorder and to be physically healthy. Both female and male SAD patients showed no significant differences compared with the controls for age and BMI (Table l). Care was taken to ensure that the patients and controls did not differ in terms of BMI and age, as both of these factors could contribute to differences in HbAI levels.
Study Design Both patients and controls participated in the study during the same winter season. Nineteen patients (13 women and six men)
and 19 controls (12 women and seven men) participated again in the summer. Subjects provided a morning blood sample at the Clinical Center of the National Institutes of Health, which analyzed the HbA] levels at the Clinical Center Laboratory using gel electrophoresis. Participants also received a mood rating on the day before the blood sample was obtained.
Statistics We compared HbA] levels in patients and controls by analysis of variance (ANOVA) with two grouping measures (gender and diagnostic group) and one repeated measure (season).
SAD
6.4 ÷ 1,8
5.9 -+ .6
Control
6.0 ± .6
6.2 ± .8
A N O V A (gender X group X season). A m a i n effect for gender was observed (F = 3.18, P < .03), with m e n having higher H b A 1 levels than w o m e n . The B M I correlated with the HbA1 level (r = .51, P < .05). W i t h i n the patient group for both w o m e n and men, there was no significant correlation b e t w e e n HbA] and the degree of depression at the time of blood sampling, as m e a s u r e d by typical or atypical symptoms. Additionally, there was no relationship b e t w e e n the reported degree of carbohydrate craving or weight gain and the S I G H - S A D and HbA~. M e n and w o m e n showed no differences in the self-report of carbohydrate craving, weight gain, and increased appetite. Because we had an a priori prediction that w o m e n with S A D might exhibit higher HbA] levels in winter, we also performed a post hoc two-way A N O V A on w o m e n across the seasons and a group t test on w o m e n in winter. There was no significant group by season effect w h e n w o m e n alone were considered. However, on the group t test, w o m e n with S A D were found to have increased HbA~ c o m p a r e d with c o n t r o l s ( 5 . 2 5 % _+ 0.75% v 5.83% ___ 0.74%, t = 2.14, df = 28, P < .05).
DISCUSSION RESULTS HbA1 levels (mean _+ SD) are reported in Table 2. N o interaction was found in a three-way
Table 1. Subject Characteristics (mean _+ SD) Group
SIGH-SAD Score
Age (yr)
BMI (kg/m 2)
25.3 + 5.3
39.7 ± 9.7
27.2 ± 9.5
38.3 + 9.5
25.4 ± 5.3
Women SAD Control Men SAD Control
24.6 ± 6.4
39.7 _+ 9.0
29.2 ± 4.6
44.6 + 8.8
28.4 ± 4.9
G i v e n that the three-way A N O V A (gender x group X season) was negative, we are u n a b l e to support our predicted hypothesis that female S A D patients have elevated HbA~ levels and therefore a b n o r m a l glucose regulation during the winter. Nevertheless, we r e c o g n i z e that the n e g a t i v e A N O V A m a y be a function of insufficient statistical power. A power analysis demonstrated that a sample size of greater than 300 patients would be needed to show a significant effect. Additionally, one must question whether such a difference, while statistically significant, would be biologically relevant. Even if, on replication, w o m e n are found to
236
NEUHAUS ET AL
have higher HbA~ levels than men, the weak effect size suggests that any disturbances in carbohydrate metabolism in SAD are probably not of major clinical significance. As such, we are forced to reject our hypothesis. However, when examined in one specific way, namely a group t test that examined women alone in winter, female SAD patients did appear to have elevated HbA1 levels compared with a group of matched controls. Nevertheless, such a statistical approach is relatively weak, and the finding would need to be replicated before it could be confidently accepted. One possible shortcoming of this study is the fact that we did not specifically measure the variable fraction, HbAlc. Since HbAlc constitutes 60% to 80% of HbA1, any variation in HbA~c is reflected in HbAI levels. As a result, HbA~ is used extensively for the clinical purpose of monitoring diabetic control. However, it is possible that the nonvariable fraction of HbA1 obscured any variation in glycosylated hemoglobin levels. As such, it would be of interest to measure HbAlc in future studies, since a
variation in this component accounts for most of the variation in HbA1 as a whole. For inclusion in the study, it was required that patients meet criteria for winter depression at the time of participation, but not for the full 8 weeks prior. As HbA1 levels are reflective of glucose control for the previous 1 to 3 months, if patients were not depressed for much of this period, it may have contributed to the negative results. While the predicted hypothesis was rejected in the present study, other studies have found gender differences in SAD patients. Intrinsic melatonin secretion in response to the lengthening winter night differed between SAD women and men. 15 In SAD patients, plasma prolactin levels, ~6-~8electroretinographic b-wave amplitudes, 19 and changes in the eye blink rate in response to light therapy2° also showed gender differences. These findings support the concept that SAD manifests different pathophysiological changes in women and men. It would thus appear that in future studies of SAD patients, separate analyses according to gender are warranted.
REFERENCES 1. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Wehr TA. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 1984;41:72-80. 2. Kasper S, Wehr TA, Bartko JJ, Gaist PA, Rosenthal NE. Epidemiological findings of seasonal changes in mood and behavior: a telephone survey of Montgomery County, Maryland. Arch Gen Psychiatry 1989;46:823-833. 3. Leibenhift E, Hardin TA, Rosenthal NE. Gender differences in seasonal affective disorder. Depression 1995;3:13-19. 4. Ernst C, Angst J. The Zurich Study XII. Sex differences in depression: evidence from longitudinal epidemiological data. Eur Arch Psychiatry Clin Neurosci 1992;241:222-230. 5. Young MA, Scheftner WA, Fawcett J, Klermann GL. Gender differences in the clinical features of unipolar major depressive disorder. J Nerv Ment Dis 1990;178:200-203. 6. Frank E, Carpenter LL, Kupfer DJ. Sex differences in recurrent depression: are there any that are significant? Am J Psychiatry 1988;145:41-45. 7. Angst J, Dobler-Mikola A. Do the diagnostic criteria determine the sex ratio of depression? J Affect Disord 1984;7: 189-198. 8. Rosen LN, Rosenthal NE. Seasonal variations in mood and behavior in the general population: a factor analytic approach. Psychiatry Res 1991;38:271-283. 9. Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med 1993;119:655-660.
10. Krauchi K, Keller U, Leonhardt G, Haug HJ, Brunner DP, Hetsch C, et al. Depressed SAD patients exhibit impaired insulin-glucose homeostasis and altered palatability of sucrose in winter. Abstract presented at the Sixth Annual Meeting of the Society for Light Treatment and Biological Rhythms; June 23-24, 1994; Bethesda, MD. 11. Nathan DM, Singer DE, Hurzthal K, Goodson JD. The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 1984;310:341-346. 12. Hinde FR, Standen PJ, Mann NP, Johnston DI. Seasonal variation of hemoglobin A1 in children with insulin-dependent diabetes mellitus. Eur J Pediatr 1989;148:597-599. 13. Ferrie CD, Sharpe TC, Price DA, Surtees RA. Seasonal variation of glycosylated hemoglobin. Arch Dis Child 1987;62: 959-960. 14. Williams JBW, Link MJ, Rosenthal NE, Amira L, Terman M. Structured Interview Guide for the Hamilton Depression Rating Scale: Seasonal Affective Disorder Version. New York, NY: New York State Psychiatric Institute, 1992. 15. Wehr TA. Melatonin and seasonal rhythms. J Biol Rythms 1997;12:517-526. 16. Oren DA, Levendosky AA, Kasper S, Duncan CC, Rosenthal NE. Circadian profiles of cortisol, prolactin and thyrotropin in seasonal affective disorder. Biol Psychiatry 1996;39:157-170. 17. Depue RA, Arbisi P, Krauss S, Iacono WG, Leon A, Muir R, et al. Seasonal independence of low prolactin concentration and high spontaneous eye blink rates in unipolar and bipolar II
GLYCOSYLATED HEMOGLOBIN AND CONTROLS IN SAD
seasonal affective disorder. Arch Gen Psychiatry 1990;47:356364. 18. Arbisi PA, Depue RA, Spoont MR, Leon A, Ainswith B. Thermoregulatory response to thermal challenge in seasonal affective disorder: a preliminary report. Psychiatry Res 1993;28: 323-334.
237
19. Lam RW, Beattie CW, Buchanan A, Mador JA. Electroretinography in seasonal affective disorder. Psychiatry Res 1992;43:55-63. 20. Barbato G, Moul DE, Schwartz PJ, Rosenthal NE, Oren DA. Spontaneous eye-blink rate in winter seasonal affective disorder. Psychiatry Res 1993;47:79-85.