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Abstracts of Selected Articles
The following are abstracts of selected articles written or co-authored by Dr. Rosenthal. For a full listing of Dr. Rosenthal's articles, see Publications.
Description of Seasonal Affective Disorder (SAD)
Rosenthal NE, Lewy AJ, Wehr TA, Kern HE, Goodwin FK. "Seasonal cycling in a bipolar patient." Psychiatry Research 8:25-31, 1983.
ABSTRACT: We describe a bipolar patient with seasonal cycles of depression and hypomania. A tally of his notebook pages provides us with an indirect record of his moods. We discuss mechanisms for seasonal mood cycles.
Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA. "Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy." Archives of General Psychiatry 41:72-80, 1984.
ABSTRACT: Seasonal affective disorder (SAD) is a syndrome characterized by recurrent depressions that occur annually at the same time each year. We describe 29 patients with SAD; most of them had a bipolar affective disorder, especially bipolar II, and their depressions were generally characterized by hypersomnia, overeating, and carbohydrate craving and seemed to respond to changes in climate and latitude. Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave (delta) sleep. Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect.
Rosenthal NE. "This Week's Citation Classic: A decade of SAD and light therapy." Current Contents, Number 10, March 8, 1993.
We described 29 patients with recurrent fall-winter depressions, and treated 11 patients with enhanced environmental lighting in a controlled crossover study. We called the syndrome seasonal affective disorder (SAD) and outlined future research directions. [The SSCI® and the SCI® indicate that this paper has been cited in more than 385 publications.]
Schwartz PJ, Brown C, Wehr TA, Rosenthal NE. "Winter SAD: A follow-up study of the first 59 patients of the NIMH seasonal studies program." American Journal of Psychiatry 153(8):1028-1036, 1996.
ABSTRACT: Objective: The purpose of this study was to characterize the long-term course of patients with seasonal affective disorder. Method: The first 59 patients with winter seasonal affective disorder who had entered winter protocols were retrospectively followed up after a mean interval of 8.8 years. Detailed life charts were constructed through use of a semistructured interview and collateral records. Results: The disorder of 25 patients (42%) remained purely seasonal, with regular recurrences of winter depression and no depression or treatment through any summer. The course of illness was complicated by varying degrees of nonseasonal depression in 26 patients (44%). The disorders of eight patients (14%) had fully remitted. Certain features of the group with complicated seasonal affective disorder suggested that they were more severely ill. Twenty-four patients (41%) continued to use light treatment regularly throughout the follow-up period. Light treatment was preferred to medication for winter recurrences, although antidepressants had been used in the winter by most (63%) of the patients who still used lights at follow-up. Conclusions: The pattern of winter depressions and summer remissions remained fairly persistent over time in this group of patients. The temporal distribution of depressive episodes both within and across individual patients was consistent with the results of several recent follow-up studies of seasonal affective disorder, providing support for the predictive and construct validity of the Rosenthal et al. diagnosis of winter seasonal affective disorder. Light treatment, while remaining a safe and satisfactory treatment for many, may be insufficient for more severely ill patients. The appearance of nonseasonal depressions in patients with winter seasonal affective disorder may be associated with greater severity of illness and less responsiveness to light treatment.
Antidepressant Effects of Light
Rosenthal NE, Sack DA, Carpenter CJ, Parry BL, Mendelson WB, Wehr TA. "Antidepressant effects of light in seasonal affective disorder." American Journal of Psychiatry 142:163-170, 1985.
ABSTRACT: The authors treated winter depression in 13 patients with typical seasonal affective disorder by extending the length of winter days with bright and dim light in the morning and evening in a balanced-order crossover study. Bright light had a marked antidepressant effect, whereas the dim light did not. This response could not be attributed to sleep deprivation. Subsequent pilot studies indicated that bright evening light alone is probably also effective. Several patients were able to maintain the antidepressant response throughout the winter months by continuing daily light treatments.
Wehr TA, Rosenthal NE, Sack DA, Gillin JC. "Antidepressant effects of sleep deprivation in bright and dim light." Acta Psychiatrica Scandinavica 72: 161-165, 1985.
ABSTRACT: In order to test whether exposure to bright artificial light at night is a necessary condition for the antidepressant response to sleep deprivation therapy, five patients were totally sleep-deprived on two separate nights, once in very bright light and once in nearly total darkness. During the day after the sleep-deprivation night patients were found to have responded equally well to sleep deprivation in both conditions. During the sleep-deprivation night, however, antidepressant responses may have been greater in the bright light condition. Thus, light at night is not necessary for the antidepressant response to sleep deprivation, but we cannot rule out the possibility that the effects of light exposure and sleep deprivation are additive or that exposure to light at some time after sleep deprivation begins (including the following day) is necessary for the response.
James SP, Wehr TA, Sack DA, Parry BL, Rosenthal NE. "Treatment of seasonal affective disorder with light in the evening." British Journal of Psychiatry 147: 424-428, 1985.
ABSTRACT: A cross-over comparison study of exposure, in the evenings only, to bright versus dim light was carried out on nine female patients with seasonal affective disorder. A significant antidepressant effect of the bright lights was shown. No consistent observable effects were produced by the dim lights. These results support earlier studies demonstrating the efficacy of bright light given morning and evening. The antidepressant effect of light is not mediated by sleep deprivation, and the early morning hours are not crucial for a response.
Wehr TA, Sack DA, Jacobsen F, Tamarkin L, Arendt J, Rosenthal NE. "Phototherapy of seasonal affective disorder: Time of day and suppression of melatonin are not critical for antidepressant effects." Archives of General Psychiatry 43:870-875, 1986.
ABSTRACT: Seasonal affective disorder is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). In winter, depressed patients with seasonal affective disorder respond to daily treatments with five to six hours of bright artificial light in two to three days. They relapse two to three days after light is with-drawn. In this study, carefully controlled experimental conditions were used to determine whether phototherapy acts via a photoperiodic mechanism in which the timing of light is critical for its therapeutic effect. Photoperiodism is a common regulatory mechanism in animal seasonal rhythms and depends for its effect on light-induced changes in the pattern of nocturnal melatonin secretion. The results reported herein of "skeleton photoperiod" experiments indicate that the efficacy of phototherapy may not depend on its timing or its effect on melatonin secretion.
Wehr TA, Skwerer RG, Jacobsen FM, Sack DA, Rosenthal NE. "Eye- versus skin-phototherapy of seasonal affective disorder." American Journal of Psychiatry 144:753-757, 1987.
ABSTRACT: In winter, depressed patients with seasonal affective disorder respond to treatment with bright artificial light (phototherapy). The authors found that the antidepressant effects of phototherapy were much greater for ten patients when light was applied to the eyes than when it was applied to the skin, suggesting that its effects may be mediated by the eyes. The identification of a probable anatomical route of entry is clinically relevant and an important clue for further investigations of the mechanism of phototherapy. However, patients' expectations nearly always predicted the outcome, leaving open the possibility that the expectations were responsible for their responses.
Kasper S, Rogers SLB, Yancey A, Schulz PM, Skwerer RG, Rosenthal NE. "Phototherapy in individuals with and without subsyndromal seasonal affective disorder." Archives of General Psychiatry 46(9): 837-844, 1989.
ABSTRACT: Antidepressant and energizing effects of bright light exposure (phototherapy) have been widely reported to occur in patients with seasonal affective disorder. We have attempted to evaluate whether other segments of the population might benefit from phototherapy, most notably individuals with subsyndromal seasonal affective disorder, as well as healthy individuals with no winter difficulties (controls). We have studied 20 subjects in each of these two categories and have found that bright artificial light did not alter mood and behavior in controls. In contrast, individuals with subsyndromal seasonal affective disorder responded favorably to treatment with bright environmental light. A dose of 5 hours of bright light exposure, divided between morning and evening, was more effective than 2 hours of exposure. This finding may have practical implications for establishing optimal environmental lighting conditions for those individuals whose winter difficulties do not meet criteria for seasonal affective disorder.
Oren D, Brainard GC, Johnston S, Joseph-Vanderpool JR, Sorek E, Rosenthal NE. "Phototherapy of seasonal affective disorder with green versus red light." American Journal of Psychiatry 148(4): 509-511, 1991.
ABSTRACT: Objective: This study sought to determine whether an equal photon density of green light is superior to red light in treating seasonal affective disorder. Method: After recruitment through the media, 20 outpatients with seasonal affective disorder participated in a balanced-order crossover trial of 1 week of green light therapy compared with 1 week of red light therapy. Each treatment consisted of 2 hours of daily light treatment at home in the early morning. Ultraviolet light was excluded from both treatment conditions. The photon densities of the two treatments (2.3 X 10 [to the 15th power superscript] phototons/sec per cm [squared, superscript]) were similar to those used in previous studies of therapy with 2500-lux white light. Fourteen patients completed the study. At least 1 week separated each treatment period to allow time for relapse. Effectiveness of treatment was assessed by analysis of variance of changes in ratings on the Hamilton Rating Scale for Depression. Results: Although patients' expectations of the two treatments were similar, green light induced greater antidepressant effects than red lights. A sequence by Color interaction was also demonstrated. Conclusions: Green light provides a treatment effect superior to that of red light and similar to that seen in previous studies with white light. These results are consistent with the hypothesis that retinal photoreceptors mediate the antidepressant response in seasonal affective disorder. Identifying optimal wavelengths for light treatment is important in optimizing phototherapy efficacy.
Oren DA, Shannon NJ, Carpenter CJ, Rosenthal NE. "Usage patterns of phototherapy in seasonal affective disorder." Comprehensive Psychiatry 32(2): 147-152, 1991.
ABSTRACT: We mailed a questionnaire to patients affected with seasonal affective disorder (SAD) to determine patterns of self-selected light use and efficacy of treatment. Data obtained from 127 patients who responded indicate that despite, inconvenience and other use-limiting factors, many patients with SAD derive sustained benefit from phototherapy over months. No consistent pattern or duration of effective treatment emerged. Development of a less cumbersome means of delivering phototherapy and reimbursement by insurance companies remain concerns to patients.
Postolache TT, Hardin TA, Myers FS, Turner EH, Yi LY, Barnett RL, Matthews JR, Rosenthal NE. "Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder." American Journal of Psychiatry 155(11):1614-1616, 1998.
ABSTRACT: Objective: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. Method: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. Results: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. Conclusions: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.
Oren DA and Rosenthal NE. "Light Therapy." In Glen O. Gabbard, M.D. (Editor-in-Chief), Treatments of Psychiatric Disorders, Third Edition. Volume 2, Chapter 44, pp. 1295-1306. Washington, DC. American Psychiatric Publishing, Inc. 2001.
A comprehensive description of light therapy theory and practice, this chapter contains information on the following subjects:
- Diagnostic indications and contraindications to light therapy;
- Evidence for efficacy, including: acute-phase treatment and maintenance/continuation therapy;
- Formal aspects of light therapy;
- Novel treatment devices;
- Practical aspects of light therapy.
Conclusions: Light therapy is widely regarded as useful for patients with SAD. Furthermore, there is evidence that it may prove to be a versatile form of treatment, useful also in persons with other types of mood disorders and persons with sleep and eating disorders. Light therapy may be used either alone or in conjunction with medications. It can be titrated like a medication, both with regard to dosage (duration and intensity) and timing of administration. Our understanding of light therapy and of the techniques and technologies involved in administering such therapy has advanced significantly over the past 20 years. There is every reason to expect that such progress will continue.
Many resources exist to keep interested clinicians and researchers up to date. These include a professional society, the Society for Light Treatment and Biological Rhythms (http://www.sltbr.org), and commercial companies that distribute light therapy devices and information about them. For further information the reader is referred elsewhere (Rosenthal 1998; Rosenthal and Blehar 1989; Zulman and Oren 1999).
How common is SAD?
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." Archives of General Psychiatry 46(9): 823-833, 1989.
ABSTRACT: Patterns of seasonal changes in mood and behavior in Montgomery County, Maryland were evaluated in randomly selected household samples by lay interviewers using a telephone version of the Seasonal Pattern Assessment Questionnaire. The method for selecting the same unit was random-digit dialing. We found that 92 percent of the survey subjects noticed seasonal changes of mood and behavior to varying degrees. For 27 percent of the sample, seasonal changes were a problem and 4.3 percent to 10 percent of subjects, depending on the case-finding definition, rated a degree of seasonal impairment equivalent to that of patients with seasonal affective disorder. The seasonal pattern of "feeling worst" exhibited a bimodal distribution with a greater winter and a substantially lower summer peak (ratio 4.5:1). Younger women who have a problem with seasonal changes and who feel worse on short days tended to exhibit the highest seasonality scores. It is apparent from our study that seasonal affective disorder represents the extreme end of the spectrum of seasonality that affects a large percentage of the general population. The influence of environmental factors on mood disorders and mood changes in the general population might provide valuable insight into pathogenesis, treatment, and prevention of affective illness.
Rosen LN, Targum, SD, Terman M, Bryant, MJ, Hoffman H, Kasper SF, Hamovit JR, Docherty JP, Welch B, Rosenthal NE. "Prevalence of seasonal affective disorder at four latitudes." Psychiatry Research 31:131-144, 1990.
ABSTRACT: The Seasonal Pattern Assessment Questionnaire (SPAQ) was mailed to a sample population balanced for sex and randomly selected from local telephone directories in four areas: Nashua, NH, New York, NY, Montgomery County, MD and Sarasota, FL. On the basis of responses to this questionnaire, prevalence rates of winter seasonal affective disorder (winter SAD), summer seasonal affective disorder (summer SAD), and subsyndromal winter SAD were estimated for the four areas. Rates of winter SAD and subsyndromal SAD were found to be significantly higher at the more northern latitudes, while no correlation was found between latitude and summer SAD. The positive correlation between latitude and prevalence of winter SAD applied predominantly to the age groups over 35.
Hardin TA, Wehr TA, Brewerton T, Kasper S, Berretini W, Rabkin J, Rosenthal NE. "Evaluation of seasonality in six clinical populations and two normal populations." Journal of Psychiatric Research 25:75-87, 1991.
ABSTRACT: The Seasonal Pattern Assessment Questionnaire (SPAQ) was used to evaluate retrospectively self-reported seasonal changes in mood and behavior (seasonality) of two normal and six clinical populations; patients with winter-seasonal affective disorder (SAD), summer-SAD, eating disorders, bipolar affective disorder, major depressive disorder and subsyndromal winter-SAD. The SPAQ successfully discriminated between groups expected to have high seasonality scores, such as winter-SAD, summer-SAD and subsyndromal winter-SAD, and normal controls. Bipolars and major depressives had normal seasonality scores. Patients with eating disorders had unexpectedly high scores. There was a general tendency for all groups to eat and sleep more and to gain weight in the winter. The implications of these findings are discussed.
Ozaki N, Ono Y, Ito A, Rosenthal NE. "The prevalence of seasonal difficulties among Japanese civil servants." American Journal of Psychiatry 152:1225-1227, 1995.
Ozaki N, Ono Y, Ito A, Rosenthal NE. "The prevalence of seasonal difficulties among Japanese civil servants." American Journal of Psychiatry 152:1225-1227, 1995.
ABSTRACT: Objective: Most prevalence studies of seasonal changes in mood and behavior have come from Western countries. The authors' goal was to determine the prevalence of seasonal changes in mood and behavior in a randomly selected group of Japanese workers. Method: They administered a Japanese translation of the Seasonal Pattern Assessment Questionnaire to 1,276 civil servants in Nagoya, Japan. Results: The estimated prevalence of winter seasonal affective disorder was 0.86%, the estimated prevalence of winter subsyndromal seasonal affective disorder was 0.86%, the estimated prevalence of summer seasonal affective disorder was 0.95%, and the estimated prevalence of summer subsyndromal seasonal affective disorder was 2.12%. Conclusions: The authors conclude that seasonal changes in mood and behavior occur in Japan, but at a lower frequency and with a different profile than in the United States or Europe.
Han L, Wang K, Du Z, Cheng Y, Simons JS, Rosenthal NE. "Seasonal variations in mood and behavior among Chinese medical students." American Journal of Psychiatry 157(1):133-135, January 2000.
ABSTRACT: Objective: The goal of this study was to estimate the frequency of seasonal variations in mood and behavior among Chinese medical students. METHOD: A total of 1,358 medical students were surveyed with Chinese versions of the Seasonal Pattern Assessment Questionnaire and the Beck Depression Inventory in Jining, China. RESULTS: The mean global seasonality score was 8.3 (SD=3.6) out of a possible 24; 81.7% (N=1,110) of the subjects reported some trouble adapting to changing seasons. Summer difficulties were more common than winter difficulties by a ratio of 3:2; estimated rates of summer seasonal affective disorder and subsyndromal seasonal affective disorder were 4.4% and 8.0%, respectively, compared with corresponding winter rates of 2.4% and 5.7%. CONCLUSIONS: These results suggest that seasonal variations in mood and behavior are common in China. The predominance of summer difficulties stands in contrast to that in most Western studies and is consistent with the only other published study performed in Asia.
Han L, Wang K, Cheng Y, Du Z, Rosenthal NE, Primeau F. "Summer and winter patterns of seasonality in Chinese college students: a replication." Compr. Psychiatry 41(1):57-62, Jan-Feb 2000.
ABSTRACT: The goal of this study is to replicate an earlier epidemiological finding of seasonal changes in mood and behavior among Chinese medical students using an independent study population. Three hundred nineteen college students were surveyed with a Chinese version of the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI) in Jining, China, during March of 1996. The frequency of seasonal patterns and prevalence rates of seasonal affective disorder (SAD) were estimated and compared with data from the medical student survey conducted in the same city. The mean Global Seasonality Score (GSS) of this college student sample was 9.9 +/- 4.9; 84% of the subjects reported some problems with the changing seasons. Summer difficulties were more prevalent than winter difficulties by a ratio of 1.9 to 1 (38.9% v 20.1%). The estimated rates of summer SAD and subsyndromal-SAD (s-SAD) were 7.5% and 11.9%, respectively, as compared with the corresponding winter figures of 5.6% and 6.3%. In addition, the prevalence estimates of winter pattern or winter SADs were higher in males than in females, but the corresponding summer figures showed no gender difference. Compared with the data from the medical student survey, this college student sample had a higher GSS (P < .01) but comparable summer to winter and female to male ratios for the prevalence of SADs (P > .05). These results replicate our previous findings that seasonal problems are common in China, but the predominant problems are summer difficulties rather than winter difficulties, and there is no female preponderance in the prevalence estimates of such problems. Both findings stand in contrast to most Western studies but are consistent with the only other published study performed in the Orient.
Palinkas LA, Houseal M, Rosenthal NE. "Subsyndromal seasonal affective disorder in Antarctica." Journal of Nervous Mental Disease 184(9):530-534, 1996.
ABSTRACT: The seasonality of depressed mood was examined in 70 men and women who spent the 1991 austral winter at three American research stations in Antarctica. Seasonal Pattern Assessment Questionnaire global seasonality scores increased significantly from late summer (February/March) to midwinter (July/August; p < .001). Only one case of seasonal affective disorder (SAD) was found during midwinter, but the prevalence of subsyndromal SAD increased significantly, from 10.5 to 28.4 per 100, during this period. Station latitude was significantly associated with SAD-specific symptoms and global Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version scores in midwinter and in early spring (October). The results suggest that even clinically normal individuals are likely to experience symptoms of subsyndromal SAD in high latitude environments, that these variations become more pronounced with increasing latitude, and that they can be detected through repeated administrations of instruments such as the Seasonal Pattern Assessment Questionnaire and Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective DisordersVersion.
SAD and Light Therapy in Children and Adolescents
Rosenthal NE, Carpenter CJ, James SP, Parry BL, Rogers SLB, Wehr TA. "Seasonal affective disorder in children and adolescents." American Journal of Psychiatry 143: 356-358, 1986.
ABSTRACT: The authors studied seven children with symptoms of seasonal affective disorder. During the winter months the children regularly experienced irritability, fatigue, school difficulties, sadness, and sleep changes as well as other symptoms of seasonal affective disorder found in adults. An open trial of bright environmental light reversed many of these symptoms and improved mood and psycho-social functioning in the winter months. School counselors and therapists should consider seasonal affective disorder in the differential diagnosis of children with school difficulties that are most prominent in the fall-winter semester.
Swedo SE, Pleeter JD, Richter DM, Hoffman CL, Allen AJ, Hamburger SD, Turner E, Yamada EM, Rosenthal NE. "The rates of seasonal affective disorder in children and adolescents." American Journal of Psychiatry 152(7):1016-1019, 1995.
ABSTRACT: Objective: The authors estimated the frequency of seasonal affective disorder in children and adolescents and examined the relationship of this rate to age and pubertal status. Method: A modified version of the Seasonal Pattern Assessment Questionnaire was distributed to 2,267 students at a middle school and a high school in a suburb of Washington, DC. A case diagnosis was made if the respondent scored over 18 and also indicated that the change of seasons was at least a "pretty bad" problem. Results: A total of 1,871 questionnaires (82.5%) were returned. Sixty probable cases of seasonal affective disorder (3.3%) were identified among the 1,835 surveys analyzed. Age was directly correlated with the frequency of seasonal affective disorder, and the rate was higher in postpubertal girls. Differences between the subjects with and without identified cases of seasonal affective disorder were seen in the symptom endorsement patterns, particularly for "feel worst," "least energy," "most irritable," and "socialize least." Conclusions: These pilot data suggest that between 1.7 percent and 5.5 percent of nine- to nineteen-year old children may have seasonal affective disorder. Further research is warranted, particularly that which examines the relationship between seasonal affective disorder and puberty.
Swedo SE, Allen AJ, Glod CA, Rosenthal NE, Teicher M, Richter D, Hoffman C, Brown C, Clark CH. "A controlled trial of light therapy for the treatment of pediatric seasonal affective disorder." Journal of the American Academy of Child and Adolescent Psychiatry 36(6):816-821, 1997.
ABSTRACT: Objective: To evaluate the efficacy of light therapy for the treatment of pediatric seasonal affective disorder (SAD). Method: 28 children (aged 7 to 17 years) at two geographically distinct sites were enrolled in a double-blind, placebo-controlled, crossover trial of bright-light treatment. Subjects initially entered a week-long baseline period during which they wore dark glasses for an hour a day. They were then randomly assigned to receive either active treatment (1 hour of bright-light therapy plus 2 hours of dawn simulation) or placebo (1 hour of clear goggles plus 5 minutes of low-intensity dawn simulation) for 1 week. The treatment phase was followed by a second dark-glasses phase lasting 1 to 2 weeks. After this phase, the children received the alternate treatment. Response was measured using the parent and child versions of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version (SIGH-SAD). Results: Data were analyzed as change from baseline SIGH-SAD-P total depression scores were significantly decreased from baseline during light therapy compared with placebo (one-way analysis of variance, p = .009), and no differences were found between the placebo and control phases. Subscores of atypical and typical depression were also significantly decreased during the active treatment (p = .004 and .028, respectively). A similar trend was noted with the SIGN-SAD-C, but this did not reach significance. At the end of the study, 78% of the parents questioned and 80% of the children questioned rated light therapy as the phase during which the child "felt best." Conclusion: Light therapy appears to be an effective treatment for pediatric SAD.
Giedd JN, Swedo SE, Clark CH, Rosenthal NE. "Pediatric seasonal affective disorder: A follow-up report." Journal of American Academy of Child and Adolescent Psychiatry 37:2, 1998.
ABSTRACT: Six subjects who as children had received a diagnosis of seasonal affective disorder consented to participate in a seven-year follow-up study. Structured and semistructured interviews were conducted to assess the course of illness, response to treatment, and current clinical state. Seasonal patterns of symptoms and response to light therapy remained relatively stable over a seven-year period. Two subjects were using adjunctive fluoxetine. Seasonal affective disorder can occur in children and adolescents, responds to light therapy, and should be considered in the differential diagnosis of pediatric affective symptoms or cyclic school performance.
Summer Depression (or Summer SAD)
Wehr TA, Sack DA, Rosenthal NE: "Seasonal affective disorder with summer depression and winter hypomania." American Journal of Psychiatry 144: 1602-1603, 1987.
ABSTRACT: The authors describe 12 patients who regularly became depressed in summer. This pattern is opposite to one the authors previously described, in which patients became depressed in winter and responded to treatment with light. Temperature may influence some summer depressions.
SAD and Melatonin
Wehr TA, Duncan WC, Sher L, Aeschbach D, Schwartz PJ, Turner EH, Postolache TT, Rosenthal NE. "A circadian signal of change of season in patients with seasonal affective disorder." Archives of General Psychiatry 58:1108-1116, December 2001.
ABSTRACT: Background: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. Methods: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each session. Results: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in summer (9.0+1.3 vs 8.4+1.3 hours. P=.001) but in healthy volunteers there was no change (9.0+1.6 vs 8.9+1.2 hours; P=.5). Conclusions: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder.
SAD and Brain Serotonin
Garcia-Borreguero D, Jacobsen FM, Murphy DL, Joseph-Vanderpool JR, Chiara A, and Rosenthal NE. "Hormonal responses to the administration of m-chlorophenyl-piperazine in patients with seasonal affective disorder and controls." Biological Psychiatry 37(10):740-749. 1995.
ABSTRACT: We report on the plasma cortisol and prolactin responses to the serotonergic agonist m-CPP (0.1 mg/kg) in 10 patients with winter seasonal affective disorder (SAD) and 10 controls during the winter, in both untreated and bright light-treated conditions; and on 8 other SAD patients and 8 other controls during the summer. Following m-CPP infusion, untreated patients had exaggerated prolactin (p < .05) and cortisol (p < .05) responses compared to controls. Light treatment significantly reduced responses of both hormones to m-CPP (prolactin: p < .01; cortisol: p < .01). When untreated winter subjects and summer subjects were compared, cortisol, but not prolactin responses to m-CPP were found to be higher in patients than in controls during the winter, and lower in patients than in controls during the summer (diagnosis by season: p < .05). These results are consistent with those of our previous report on the behavioral responses to m-CPP in the same patients and suggest an abnormality in serotonergic function in untreated SAD patients in winter, which is normalized following treatment with light therapy and naturally during the summer.
Schwartz PJ, Murphy DL, Garcia-Borreguero D, Oren DA, Moul DE, Ozaki N, Snelbaker AJ, Wehr TA, Rosenthal NE. "Effects of Meta-chlorophenylpiperazine infusions in patients with Seasonal Affective Disorder and healthy control subjects: diurnal responses and nocturnal regulatory mechanisms." Archives of General Psychiatry 54(4):375-385. 1997.
ABSTRACT: Background: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. Methods: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. Results: Meta-chlorophenyl-piperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. Conclusions: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnor-malities. The improve-ments in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.
Neumeister A, Turner EH, Matthews JR, Postolache TT, Barnett RL, Rauh M, Vetticad RG, Kasper S, Rosenthal NE. "Effects of Trypophan depletion versus catecholamine depletion in patients with seasonal affective disorder remitted on light therapy." Archives of General Psychiatry 55:524-530, 1998.
ABSTRACT: BACKGROUND: Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms, the potential role, if any, of catecholaminergic pathways has not been fully explored. METHODS: Sixteen patients with seasonal affective disorder who had responded to a standard regimen of daily 10000-lux light therapy were enrolled in a double-blind, placebo-controlled, randomized crossover study. We compared the effects of trypto-phan depletion with catecholamine depletion and sham depletion. Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan. Administration of the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine was used to deplete catecholamines. Diphenhydramine hydrochloride was used as an active placebo during sham depletion. The effects of these interventions were evaluated with measures of depression, plasma tryptophan levels, and plasma catecholamine metabolites. RESULTS: Tryptophan depletion significantly decreased plasma total and free tryptophan levels. Catecholamine depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Both tryptophan depletion and catecholamine depletion, compared with sham depletion, induced a robust increase (P<.001, repeated-measures analysis of variance) in depressive symptoms as measured with the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version. CONCLUSIONS: The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan depletion and catecholamine depletion. These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain catecholaminergic systems may also be involved.
Schwartz PJ, Turner EH, Garcia-Borreguero D, Sedway J, Murphy DL, Rosenthal NE. "Serotonin hypothesis of winter-depression: Behavioral and neuroendocrine effects of the 5HT (1A) receptor partial agonist ipsapirone in patients with seasonal affective disorder and controls." Psychiatry Research 86(1):9-28, 1999.
ABSTRACT: Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta-chlorophenylpiperazine (m-CPP). Several studies are also consistent with abnormal serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis in SAD. Here, we investigated the effects of the 5-HT1A receptor partial agonist ipsapirone, which produces behavioral effects and HPA-axis activation, to further characterize the 5-HT receptor subtype-specificity of these disturbances in SAD. Eighteen SAD patients and 18 control subjects completed two drug challenges (ipsapirone 0.3 mg/kg and placebo) separated by 3-5 days in randomized order. We measured behavioral responses with the NIMH self-rating scale, and plasma ACTH, cortisol, and prolactin concentrations. Compared with placebo, ipsapirone was associated with significant increases in self-rated 'functional deficit' and 'altered self-reality', and in each of the hormones. There were no differences between groups on any measures. The level of depression in SAD patients was inversely correlated with their ipsapirone-induced cortisol responses. There were significant drug x order effects on baseline 'anxiety' scores, ACTH and cortisol concentrations, such that subjects were significantly more stressed (higher 'anxiety', ACTH and cortisol) prior to their first challenge compared with their second. In conclusion, post-synaptic 5-HT1A receptors appear to function normally in SAD. The previously observed m-CPP-induced behavioral abnormality may be mediated by either 5-HT2C or 5-HT7 receptors.
SAD and Visual Impairment
Rosenthal NE, DellaBella P, Hahn L, Skwerer RG. "Seasonal affective disorder and visual impairment: Two case studies." Journal of Clinical Psychiatry 50(12): 469-472, 1989.
ABSTRACT: Winter depressive episodes in patients with seasonal affective disorder are induced by light deficiency and are successfully treated by enhancing environ-mental light. The authors investigated the role of abnormal visual information processing in the genesis of seasonal affective disorder symptoms by examining two patients with impaired vision and recurrent winter depressions. The first patient developed winter depressions after developing a traumatic cataract in one eye, and was helped by light therapy. The second patient, fully blind since she was 1 year old, nonetheless suffered as an adult from winter depressions, which responded to bright -- but not to dim -- light treatment. The authors discuss the implications of these findings.
Rapid-cycling mood disorders
Wehr TA, Sack DA, Rosenthal NE, Cowdry RW. "Rapid cycling affective disorder: Contributing factors and treatment responses in 51 cases." American Journal of Psychiatry, 145: 179-184, 1988.
ABSTRACT: For 51 patients with rapid cycling affective disorder, clinical and family history data indicated that the illness was phenotypically and genetically related to more typical forms of affective disorder, was characterized by a bipolar course (100%), and was more common in women (92%). Manic-depressive cycles were separate from menstrual cycles. At the time of onset of rapid cycling, 73% of the patients were taking antidepressant drugs; the continuation of rapid cycling was associated with antidepressant drug therapy in 51% of the patients. Although most patients had been referred to a research ward because they were considered to be refractory to treatment, 37% attained essentially complete remissions, usually during treatment with lithium and/or monoamine oxidase inhibitors.
Delayed sleep phase syndrome
Rosenthal NE, Joseph-Vanderpool JR, Levendosky AA, Johnston SH, Allen R, Kelly KA, Souetre E, Schulz PM, Starz BK. "Phase-shifting effects of bright morning light treatment in patients with delayed sleep phase syndrome." Sleep 13(4): 354-361, 1990.
ABSTRACT: bright light has recently been shown to have phase-shifting effects on human circadian rhythms. In this study we applied this effect to 20 patients with delayed sleep phase syndrome (DSPS) who were unable to fall asleep at conventional clock times and had a problem staying alert in the morning. In a controlled treatment study, we found that 2 h of bright light exposure in the morning together with light restriction in the evening successfully phase advanced circadian rhythms of core body temperature and multiple sleep patencies in these patients. This finding corroborates the importance of light for entraining human circadian rhythms.
Rosenthal NE. "Syndrome triad in children and adolescents." American Journal of Psychiatry 152(9):1402, 1995. Letter to Editor.
SAD and Response to Stress
Joseph-Vanderpool JR, Rosenthal NE, Chrousos G, Wehr TA, Kasper S, Gold PW. "Abnormal pituitary-adrenal responses to CRH in patients with seasonal affective disorder: Clinical and pathophysiological implications." Journal of Clinical Endocrinology and Metabolism 72(6): 1382-1387, 1991.
ABSTRACT: CRH has been shown to produce increased locomotion, arousal, and anorexia in experimental animals. A deficiency of CRH in patients with seasonal affective disorder could contribute to the characteristic lethargy, hypersomnia, and hyperphagia characteristic of this illness. To test this hypothesis, we studied basal plasma ACTH and cortisol levels and their responses to ovine CRH in controls and depressed patients with seasonal affective disorder before and after light treatment. Untreated seasonal affective disorder patients showed normal basal plasma cortisol and ACTH levels, but their responses to CRH tended to be delayed and were significantly reduced. When patients were studied after 9 days of light treatment, a significant increase in plasma ACTH and cortisol responses to CRH was observed. Our findings in untreated patients with seasonal affective disorder are similar to those in patients with Cushing's disease 2 weeks after transsphenoidal hypophysectomy, who uniformly show sustained suppression of their CRH neuron because of long-standing hypercortisolism.
These findings suggest that the CRH neuron of patients with seasonal affective disorder is hypofunctional. We postulate that the clinical symptomatology in patients with seasonal affective disorder could reflect deficient activity of this important arousal-producing system.
SAD and smell (Olfactory function)
Oren DA, Schwartz PJ, Turner EH, Rosenthal NE. "Olfactory function in winter seasonal affective disorder." American Journal of Psychiatry 152(10):1531-1532, 1995. Letter to Editor.
Genetics and SAD
Ozaki N, Rosenthal NE, Ullamari P, Lappalainen J, Feldman-Naim S, Schwartz PJ, Turner E, Goldman D. "Identification of two naturally occurring amino-acid substitutions of the 5-HT2A [2A are a subscript] receptor: similar prevalence in patients with seasonal affective disorder and controls." Biological Psychiatry 40:1267-1272, 1996.
ABSTRACT: We screened the 5-HT2A receptor gene coding region in 50 patients with seasonal affective disorder (SAD) using a single strand conformational polymorphism analysis and estimated the frequencies of two synonymous and two non-synonymous substitutions we detected in 70 Centre d'Etude du Polymorphism Humain (CEPH) population controls and 62 normal controls. Both of the amino acid substitutions: Ala447-Val447 and His452-Tyr452, were located within the cytoplasmic. C-terminal tail of the receptor. Rarer allele frequencies in CEPH were 0.7% and 9.3% for Val447 and Tyr452, respectively. Allele frequencies of all four polymorphisms, including the two amino acid substitutions, were not significantly different in SAD patients as compared to CEPH and normal controls. Lack of association of Val447 and Tyr452 to SAD is consistent with observations showing normal 5-HT2A receptor Ca2+ response in platelets with this disorder, however, the two 5-HT2A amino acid substitutions may lead to differences in behavioral phenotypes.
Madden PA, Heath AC, Rosenthal NE, Martin NG. "Seasonal changes in mood and behavior: The role of genetic factors." Archives of General Psychiatry 53:47-55, 1996.
ABSTRACT: BACKGROUND: Seasonal rhythms in mood and behavior (seasonality) have been reported to occur in the general population. Seasonal affective disorder, a clinically diagnosed syndrome, is believed to represent the morbid extreme of a spectrum of seasonality. Two types of seasonality have been clinically described: one characterized by a winter pattern and a second by a summer pattern of depressive mood disturbance. METHODS: By using methods of univariate and multivariate genetic analysis, we examined the relative contribution of genetic and environmental factors to the risk of seasonality symptoms that were assessed by a mailed questionnaire of 4639 adult twins from a volunteer-based registry in Australia. RESULTS: Seasonality was associated with a winter rather than a summer pattern of mood and behavioral change. In each behavioral domain (i.e., mood, energy, social activity, sleep, appetite, and weight), a significant genetic influence on the reporting of seasonal changes was found. Consistent with the hypothesis of a seasonal syndrome, genetic effects were found to exert a global influence across all behavioral changes, accounting for at least 29% of the variance in seasonality in men and women. CONCLUSIONS: There is a tendency for seasonal changes in mood and behavior to run in families, especially seasonality of the winter type, and this is largely due to a biological predisposition. These findings support continuing efforts to understand the role of seasonality in the development of mood disorders.
Rosenthal NE, Mazzanti CM, Barnett RL, Turner EH, Lam GK, Goldman D. "Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder." Journal of Molecular Psychiatry 3:175-177, 1998. xxx
ABSTRACT: Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT). the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression. We hypothesized that this short allele would also be associated with SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non-seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR and compared statistically. Patients with SAD were less likely to have the l/l genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8% vs 32.4%; P < 0.02) as compared to controls. The three 5-HTTLPR genotypes were also differentially distributed in patients and controls (P < 0.03). The SAD patients with the l/l genotype had a lower mean seasonality score than did patients with the other two genotypes (mean +/- s.d. = 15.3 +/- 2.8 vs 17.1 +/- 3.4 respectively; P < 0.02). The 5-HTTLPR short allele contributes to the trait of seasonality and is a risk factor for SAD, providing further evidence for a relationship between genetic variation in the 5-HT transporter (5-HTT) and behavior.
Enoch MA, Goldman D, Barnett R, Sher L, Mazzanti CM, Rosenthal NE. "Association between seasonal affective disorder and the 5-HT2A promoter polymorphism." Molecular Psychiatry 4(1):89-92, 1999.
ABSTRACT: Genes involved in serotonin metabolism are good candidates for the pathogenesis of seasonal affective disorder (SAD). A functional variant in the serotonin transporter promoter, 5-HTTLPR, has recently been shown to be associated with SAD and seasonality. The purpose of this study was to determine whether -1438G/A, a polymorphism in the 5-HT2A promoter, is associated with SAD and seasonality, and whether it has additive effects with 5-HTTLPR on seasonality. Sixty-seven individuals with SAD and 69 normal volunteers, all screened with the SCID and diagnosed according to DSM-III-R criteria, were genotyped for the -1 438G/A 5-HT2A promoter polymorphism. All had been previously genotyped for 5-HTTLPR and had been assessed for seasonality by the Global Seasonality Scale. There was a significant increase in the frequency of the -1438A variant allele of the 5-HT2A promoter polymorphism in SAD patients (0.47) compared to matched controls (0.36) (P < 0.01). The difference in genotype distribution was also significant (P < 0.05). We found no association between the -1438G/A polymorphism and seasonality scores, and there was no additive effect with 5-HTTLPR on seasonality. In conclusion, we have shown that the -1438G/A 5-HT2A promoter variant is associated with SAD but not with seasonality. We suggest that the association may instead be with the depressive symptoms of SAD. However, these results should be treated with caution until replicated because of the possibility of false-positive findings in case-control association studies.
Sher L, Goldman D, Ozaki N, Rosenthal NE. "The role of genetic factors in the etiology of seasonal affective disorder and seasonality." Journal of Affective Disorders 53(3):203-210, 1999.
ABSTRACT: The study of the genetic basis of seasonal affective disorder (SAD), a condition where depressions in fall and winter alternate with nondepressed periods in the spring and summer, has recently received attention. The data on the genetics of seasonal affective disorders are of three types: 1. Familiality: Studies on the prevalence of psychiatric disorders among relatives of patients with SAD suggested a familial contribution to the development of SAD; 2. Heritability: A survey of a cohort of twins showed that genetic effects exert a global influence across a variety of behavioral traits and accounted for at least 29% of the variance in seasonality in men and women; 3. Molecular genetic research: two genetic variants related to serotonergic transmission, the 5-HTTLPR and the 5-HT2A-1438G/A gene promoter polymorphisms, are associated with SAD; the former but not the latter polymorphism is related to seasonality. Future research may clarify the role of different genes in the development of SAD.
Multiple Chemical Sensitivity
Rosenthal NE. "Multiple Chemical Sensitivity: Lessons from SAD." Toxicology and Industrial Health 10:623-632, 1994.
ABSTRACT: Review. The two conditions reviewed, multiple chemical sensitivity (MCS) and seasonal affective disorder (SAD), share three important features. First, they are diagnoses made largely on the basis of patient reports. Second, they are conditions in which symptoms are reportedly elicited in vulnerable individuals by exposure to specific environmental stressors. Finally, both have been recognized for some time and have moved relatively recently into the public idea and the awareness of clinicians. Conclusion: As with SAD, MCS has been well described by multiple clinicians of different theoretical orientations working in diverse and scattered locations over the past several decades. Severe cases do not appear to be uncommon and the condition may be even more widespread in its less florid forms. A great deal of work needs to be done to do justice to those who suffer from this serious and disabling condition. We need to agree on diagnostic criteria, study its prevalence and expand our research attempts to understand and treat the condition.
Nawab SS, Miller CS, Dale JK, Greenberg BD, Friedman TC, Chrousos GP, Straus SE, Rosenthal NE. "Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls". Psychiatry Research 95(1):67-74, July 24, 2000.
ABSTRACT: Two hundred and twenty-five subjects, including normal volunteers and patients with previously documented seasonal affective disorder (SAD), chronic fatigue syndrome (CFS), Cushing's syndrome, Addison's disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported sensitivity to various chemical exposures. Patients with CFS, Addison's disease and SAD self-reported more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity than men. This report suggests that chemical sensitivity may be a relevant area to explore in certain medical and psychiatric populations. A possible relation-ship between reported chemical sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed.
St. John's Wort
Cott JM, Rosenthal NE, Blumenthal M. "St. John's Wort and Major Depression." Journal of the American Medical Association. 286(1):42, discussion 44-45. July 4, 2001. Letter to Editor.
Lithium: An Orphan Drug
Rosenthal NE. "Lithium: An orphan drug." Archives of General Psychiatry 58(10):973. October 2001. Letter to Editor.
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