Journal o/ A/fective Disorders, 21 (1991) 57-65 0 1991 Elsevier Science Publishers B.V. (Biomedical ADONIS 016503279100058A
57 Division)
0165-0327/91/$03.50
JAD 00772
Multi-center
study of seasonal affective disorders A preliminary report
in Japan.
K. Takahashi I, Y. Asano 2, M. Kohsaka 3, M. Okawa 4, M. Sasaki 5, Y. Honda 6, T. Higuchi ‘, J. Yamazaki *, Y. Ishizuka 9, K. Kawaguchi lo, T. Ohta “, K. Hanada 12, Y. Sugita 13, K. Maeda 14, H. Nagayama 15, T. Kotorii 18, K. Egashira I7 and S. Takahashi I2 ’ Division of Mental Disorders Research, National Institute of Neurosciences. NCNP, Kodaira. ’ Shukutsu Mental Hospital, Muroran. Departments of Psychtatty of s Hokkaido University, Sapporo, 4 Akita University, Akita. 5 Jtkei Unwerstty, Tokyo. e Seiwa Hospital, Neuropsychiatric Research Instrtute, Tokyo, Departments of Psychiatry OJ 7 Gunma University, Maebashi, a Saitama Medical School, More, 9 Yamanashi Medical College, Kofu, to Hamamatsu University, Hamamatsu, t’ Nagoya University, Nagoya, ” Shiga University of Medical Science, Otsu, ” Osaka Unioersity, Osaka I4 Kobe University, Kobe, ‘-s Medtcal College of Otto. Oita, t6 Kurume University, Kurume and ” University oj Occupational and Envtronmental Health, Kitakyushu. Japan (Received 26 February 1990) (Accepted 3 October 1990)
Summary A multi-center study on seasonal affective disorder (SAD) was conducted from the autumn of 1988 to the spring of 1989 with the cooperation of 16 facilities in Japan. Forty-six SAD patients were identified among 1104 respondents to our advertisements in mass media, or patients seen at the outpatient clinics. Essentially similar findings to other previous reports were obtained in terms of onset age of the first episode, duration of episode, high proportion of depression in first-degree relatives and atypical vegetative symptoms. However, a nearly equal sex ratio, together with a high proportion of unipolar depression, is characteristic of the present study. Increased appetite and carbohydrate craving were predominant only in female patients, whereas hypersomnia was prominent in both sexes. Effective response to light therapy was found in 17 SAD patients. However, a controlled study on a large number of patients is required to allow final conclusions on the efficacy of light therapy in Japanese SAD patients.
Key words:
Seasonal
affective
disorder;
Phototherapy;
Demographic
features;
Clinical
features
Introduction Address for correspondence: Kiyohisa Takahashi, M.D., Division of Mental Disorders Research, National Institute of Neurosciences, NCNP, 4-l-l Ogawahigashi. Kodaira-City, Tokyo 187, Japan.
During the past 5 years a number of research groups in North America, Europe and the South-
58
em hemisphere have reported on seasonal affective disorder (SAD). It has been demonstrated that these disorders have characteristic backgrounds and symptoms. In particular, a high incidence of female patients has been consistently ‘observed in all the studies reported. Moreover, familial loading for affective disorder is also suggested. As to symptoms, several atypical vegetative symptoms have been reported, such as hyperphagia, hypersomnia, weight gain and/or carbohydrate craving. The depressive state has been reported to be ameliorated by bright light exposure for at least 1-2 h/day. This fact has led to speculations that the psychopathological mechanism underlying the disorder may be related to photoperiodism or the phase of the circadian rhythms (Lewy et al., 1982; Rosenthal et al., 1984; James et al., 1985; Wirz-Justice et al., 1986; Hellekson et al., 1986; Jacobsen et al., 1987; Terman, 1988; Thompson and Isaacs, 1988; Boyce and Parker, 1988). It would be of interest to investigate whether Orientals are as sensitive to seasonal changes in light as Caucasians. To our knowledge no systematic study of SAD in Orientals has been reported. As there is a marked difference in skin pigmentation between the two races, it would be reasonable to conceive that this difference might be associated with differences in symptoms or incidence of SAD. With these considerations in mind, members of the Japanese research group on chronobiology, which was organized in 1986, started a multi-center survey of SAD in Japan in autumn 1988 with the support of a Research Grant from the Ministry of Education, Science and Culture (the representative of this research group is S. Takahashi). We recruited SAD patients with the help of the news media as in previous studies (Rosenthal et al., 1984; Wirz-Justice et al., 1986; Thompson and Isaacs, 1988) to investigate whether or not a group of SAD patients also exists in our country. Further, we administered light therapy to a limited number of patients, to determine whether Japanese patients might also respond to bright light. We here report the preliminary results obtained in the first year of the project between the autumn of 1988 and the spring of 1989.
Methods Recruitment of patients Patients were recruited in two different ways: first by identification of SAD in each outpatient clinic of the facilities involved in the project, and second by recruitment through nationwide or local newspapers. After publication of a scientific article describing Rosenthal’s operational criteria for SAD and SAD symptoms including specific vegetative symptoms, such as increased appetite and increased sleep, 1104 people requested questionnaires. The Japanese questionnaire, which was a modified version of the Seasonal Screening Questionnaire (SSQ) devised by Rosenthal et al. (personal communication), was sent to the respondents. When the answers to the questionnaire met the following criteria, prospective patients were referred to the nearest study facility, where they were interviewed to obtain details of their history and symptoms. (1) All depressive episodes occurred in autumn or winter. (2) At least two depressive episodes were observed in two consecutive years. (3) No depressed state was suggested during spring and summer. (4) Depression as stated by the respondents seemed to be so severe as to meet the criteria of major depression in DSM-IIIR. (5) Depressed states seemed not to be caused by any evident psychological events. In the interview onset time of each depressive episode was particularly investigated as precisely as possible to determine the variation of onset time in individuals. We have followed Rosenthal’s operational criteria for the diagnosis of SAD (1984), using DSM-IIIR criteria to evaluate major depressive episodes instead of the RDC, because the DSM-III is much more widely used in our countryThe Schedule for Affective Disorders and Schizophrenia was not systematically used. Instead, we have used DSM-IIIR to make the diagnosis bipolar or unipolar with or without hypomanic episodes. We took it for granted that these three groups correspond to RDC bipolar I, bipolar II and unipolar and compared our data with those reported by others.
Light therapy Informed consent was obtained from the patients who agreed to participate in the light therapy study. As the number of light boxes available was limited, only 17 patients underwent light therapy (10 males and seven females). Thirteen patients were inpatients, while four patients were treated in their own homes. The present pilot study was an open trial to see if phototherapy is effective in Japanese SAD patients. We therefore investigated the effect of dim light or light withdrawal as a control study in only a few cases. In the standard light therapy procedure, the patients were exposed to a light intensity of 25003000 lux for 2 h in the morning, usually between 06.00 h and 08.00 h. We adopted this light intensity, because previous papers have reported success with it in achieving an antidepressant effect. The time of day of the light exposure was also decided on the basis of previous reports (Terman et al., 1989a). The light source consisted of 12 X 20 W cool-white fluorescent tubes. Patients were instructed to sit 1 m away from the light source and to look into the light at least once a minute. As a rule, evaluation according to the Hamilton Rating Scale for Depression (HAM-D) was done by a participating researcher in the morning 1-2 days before and 1-2 weeks after the start of light therapy. The minimum entry criterion for the therapy was a HAM-D score of 10. We compared the male and female groups of our study statistically with the &i-square test. We also compared our data with those of other researchers outside Japan, using the same method. Results Clinical and demographic features of SAD in Japan Eventually 46 SAD patients were identified, 21 in the outpatient clinic and 25 via mass media recruitment. In the latter case 141 suspected cases were screened, based on the answers to the questionnaire, and referred to participating researchers. However, only 50 persons visited the facility to be interviewed. All 46 patients, 19 males and 27 females, fulfilled DSM-IIIR criteria for a history of major depressive episodes. The main reasons for exclusion after the interview were an obvious effect of
TABLE
1
WIDTH OF TEMPORAL ONSET OF THE EPISODES
WINDOW IN EACH
COVERING PATIENT
Male
Female
Total
60 days 90 days
10 (8) 6 (4)
9 (8) 6 (6)
19 (16) 12 (10)
120 days 150 days 180 days
2 (2) l(1) 0 (0)
8 (7) 3 (3) l(1)
10 (9) 4 (4) 1 (1)
Numbers episodes.
in parentheses
show patients
with more
than
THE
three
psychosocial stressors, equivocal seasonality, and lack of symptoms meeting DSM-IIIR criteria for major depression. The variation of onset time of depressive episodes in individuals is shown in Table 1. Two thirds (67%) of SAD patients manifested symptoms within a period of 90 days between September and February, the period being specific to each patient. When the window was narrowed to 60 days for each patient, as required by the definition in DSM-IIIR, the percentage decreased to 41. As shown in Table 2, SAD patients were identified all over the Japanese archipelago, from Hokkaido to Kyushu, with a latitude range of 33-42O. In the study facilities in the south (33-34” N) and the north (42-43 o N) equal numbers of SAD patients were observed. Demographic and clinical features are shown in Table 3. Although female
TABLE
2
RELATIONSHIP OF PATIENTS
BETWEEN IDENTIFIED
LATITUDE AND NUMBERS IN THE PRESENT STUDY
Latitude
City
Males
Females
(ON) 5 3
Sapporo, Muroran Akita Tokyo, Moro, Kofu. Shizuoka, Nagoya, Otsu
42-43 39.5
2 (1) 2
35-36
8 (7)
12 (11)
Osaka Kitakyushu, Ohita
34.5
5 (3)
3 (2)
2 19 (15)
4 27 (25)
Numbers episodes.
Kurume, 33-34
in parentheses
show patients
with more
than
three
TABLE
3
CLINICAL AND DEMOGRAPHIC TIENTS WITH SAD Males Number Age + SEM Age at onset (years) Number of episodes Duration of episodes Mental disorders observed SAD Affective disorder Schizophrenia Alcoholism Others
FEATURE
Females
19 35.4i 22.9 i 9.3 + 4.6 *
3.7 3.4 2.5 0.3
27 35.7 28.6 4.8 4.3
+ + f f
OF
PA-
Total 46 35.5 f 2.2 26.5 f 1.9 6.5*1.1 4.4 + 0.2
2.4 2.4 0.4 0.3
in first-degree relatives 0% 16% 53% 40% 7% 5% 7% 16% 7% 8%
10% 45% 8% 13% 8%
RDC diagnosis Bipolar I Bipolar II Unipolar
6.7% 33.3% 60.0%
10.0% 25.0% 65.0%
8.6% 28.6% 62.9%
Affect Sadness Irritability Anxiety
80% (50%) 67% (56%) 93% (53%)
80% (44%) 84% (59%) 92% (48%)
80% (47%) 78% (58%) 93% (50%)
Psychomotor depression Reduced activity Difficulty in work Reduced social function Appetite Increased Decreased Unchanged Carbohydrate
craving
Weight Increased Decreased Unchanged Sleep Increased Sleepiness daytime Numbers observed
100% (85%) 100% (93%) 100% (91%) 100% (80%) 100% (82%) 100% (81%) 100% (90%) 100% (85%) 100% (87%)
22% 22% 41% 35%
56% 24% 21% 78%
42% 23% 28% 60%
47% 6% 41%
58% 8% 27%
54% 7% 28%
70%
78%
74%
50%
52%
51%
during
in parentheses show at the first interview.
the percentage
of symptoms
patients outnumbered males, the ratio was only 1.4 : 1. Age at the time of entry into the study was 33.2 years in the former and 18-59 in the latter. Both average age of onset and duration of the depressive episodes were almost equal in the two sexes. Similarly, the occurrence of mania or hypomania during spring and summer and a family
history of mood disorder and other psychoses were observed equally in both sexes. According to their life history 8.6% of patients seemed to have experienced a manic episode, while 28.6% could be considered to have had hypomanic episodes. About 60% of patients showed a unipolar pattern. Symptoms related to psychomotor retardation, such as reduced activity, difficulty in work or reduced social activity, were observed in all patients examined during the episode of depression. Similarly a high percentage of changes in affect, such as sadness, irritability or anxiety, was also seen. However, at the entry to the study, a marked difference in the percentage of symptoms was noticed (Table 3). Changes in psychomotor activity were still numerous compared with those in affect. The incidence of overeating (0.05 < P -c 0.1) together with carbohydrate craving (P < 0.05) was higher in females than males, while no sex difference in weight increase was observed. In both sexes more than 70% of patients showed hypersomnia. Light therapy The effect of light therapy on depression is shown in Table 4. The mean percentage reduction in the HAM-D score was 50.8% with no obvious sex differences. Eight of 17 patients (47.4%) were judged to have remitted according to the dual criteria applied in the cross-center study of Terman et al. (1989b) (HAM-D score reduction of at least 50% and a post-treatment score < 8). Seven out of 17 patients (41.2%) did not satisfy both criteria. Based on the general clinical impressions of the participating researchers. although that was an unstructured subjective impression, S/10 (80%) male patients and 6/7 (85.2%) female patients benefited from light therapy. None of the patients complained of any physical trouble caused by the light therapy. Ophthalmological examination also revealed no side effects of light therapy. Discussion The present preliminary study demonstrated that SAD - a syndrome of major depression recurring annually in autumn and winter - exists over all the Japanese islands and that light therapy seems to be effective in the treatment of the
61 TABLE 4 EFFECT
OF LIGHT THERAPY Pre HAM-D
Males
Difference
Reduction rate
Physicians’ evaluation TC
GI
11 4 4 4 14 14
7 7 11 6 B 0
38.9 63.6 73.3 60.0 36.4 0.0
++ ++ ++ -
++ ++ ++ ++ + -
15 25 16 11
5 12 4 8
10 13 12 3
66.7 52.0 75.0 27.3
++ + ++ -
+ + ++ -
++ ++ ++ + -
++ + ++ ++ ++ ++ -
18 12 18 17 23 32 22 (20.2 + 6.3)
Mean
Post HAM-D
18 11 15 10 22 14
(15.7 + 4.9) Females
ON HAM-D
17.6k5.8
(8.0 + 4.3)
(7.7 * 4.1)
2 8 7 12 4 9 20
16 4 11 5 19 23 2
(8.9k5.9)
88.9 33.3 61.1 29.4 82.6 71.9 9.1
(11.758.5)
8.4 i 4.9
(47.9 k 25.3)
9.4 i 6.4
(55.Ok31.7) 50.8 f 27.4
Pre and Post HAM-D show HAM-D evaluated shortly before the start of light therapy and after l-2 weeks of light therapy, respectively. TC represents the results evaluated according to Terman’s criteria (+ + : both > 50% and < 8; + : either > 50% or x 8; - : neither 50% nor < 8). GI represents the global impression of the participating researcher.
disorder. However, further study on light therapy is required to confirm its efficacy, as the number of patients examined was not sufficient and controlled comparisons with dim light or light withdrawal were scarcely performed. For the most part we followed the operational criteria of Rosenthal et al. (1984) concerning timing of the onset of episodes and remission, consecutiveness of episodes, exclusion of an evident relationship with psychosocial events or physical or mental disorders. However, since the DSM-IIIR criteria for major depression were most acceptable to study members, we adopted them instead of RDC to evaluate the depressive state. This choice was also influenced by the introduction of the criteria for a seasonal pattern of mood disorder in DSM-IIIR. As we examined our data on the winter type of seasonal depression, we could not accept DSM-IIIR criteria in their present form. However, we also aimed to evaluate the validity of criteria
dealing with the number of episodes and the duration of the window for episode onsets. In the DSM-IIIR criteria, the window of onset and remission from the depressive episode is set at a particular 60 days of the year in individuals. We therefore examined the variation in onset time of the depressive episode in each patient, as shown in Table 1. Only 41% (or 40%) of all SAD patients examined met the criteria, suggesting that a 60 day window is insufficient to identify the disorder. If we had followed the DSM-IIIR criteria for seasonal pattern strictly, more than half of the SAD patients in Japan would have been overlooked. As to the number of episodes, we found six patients with only two episodes, who did not satisfy the DSM-IIIR criteria. There was, however, no difference in the demographic and clinical features between the patient groups with more than two and three episodes (data not shown). This fact suggests that at least two consecutive episodes in
62 TABLE
5
CHARACTERISTICS
OF A SEASONAL Japan (n=46)
AFFECTIVE U.S.A. ’ (Maryland) (n=246)
Mean age (years) Sex ratio (F : M)
35.5 1.4:1
38 4.6
Depression Mean age at first episode Mean number of episodes Mean duration of episodes
26.5 6.5 2ow
22 -
Affect Sadness Anxiety Irritability Psychomotor depression Reduced activity Reduced social function (difficulty in interpersonal relationship) Work difficulties
:1 * *
DISORDER
GROUP
AND
U.K.’
Switzerland
(n=42)
(n = 63)
(n = 23)
43.8 3.5 : 1 (49 : 14)
_ 6.7
42 9:1**
3
COMPARISONS Australia
:1 +
4
WITH
OTHER
SERIES
U.S.A. 5 (New York) (n =163)
U.S.A. 6 (Alaska) (n=17)
39.3 5.O:l * (136 : 27)
38 15.7:
1* *
31.5 -
23W
24 17 18W
80% 93% 78%
96% 87% 86%
96% 86% 77%
91% = 86% a 82% a
78.3% 82.6% 82.6%
95% 76% 84%
100%
95%
100%
100% L
87.0%
97%
100% 100%
93% 86%
98% 100%
100% a 100% =
95.7% 95.7%
90% 87%
-
2.5% 23.3% 47.2% 27% (Minor)
0% 82% * 18%
47.8% 34.8% 47.8% 30.5% 78.3% 39.1%
77.0% * 9.3% * 77.6% 5.0% 88.2% 71.4%
_
82.6%
6% ** 9% 32% -
33% -
58%
43%
2.5M (23W)
RDC diagnosis Bipolar I Bipolar II Unipolar
8.6% 28.6% 63.8%
7% 81% ** 12% **
18% 37% 45%
Vegetative symptoms Appetite increased Appetite decreased Weight increased Weight decreased Carbohydrate craving Sleep increased
42% 23% 54% 23% 60% 74%
71% * 18% 76% 10% * 72% 83%
74% 16% 84% 6% 82% 78%
45% 45% 55% 23% 77% 82%
Previous treatment Inpatient Lithium Antidepressants Benzodiazepines No treatment
22% 3% 63% 60% 33%
11% 10% 42% -
18% 16% * 49% 40% 51%
8% 12% 66% -
26%
W, weeks, M, months. * P < 0.05, * * P < 0.01 compared with the present data (Japan). References: 1: Rosenthal, 1987 (cited in Hellekson, 1989); 2: Thompson Parker, 1988; 5: Terman et al., 1989; 6: Hellekson, 1989. a Cited from Wire-Justice et al.. 1987.
-
0% = 90% a (8%) 10% a (90%) (Number in parentheses shows percentage according to clinical diagnosis)
= a = = = a
26%
and Isaacs, 1988; 3: Win-Justice
21.1 4.8M (18W)
25 -
-
8%
et al., 1989; 4: Boyce and
63
winter may be sufficient to make the diagnosis of SAD, although admittedly the number of patients in our study was too small to allow a final conclusion. Although a strong latitude dependence of this syndrome has been reported (Rosenthal et al., 1988) the numbers of patients identified in our study were distributed equally from Hokkaido island (42-45 ON) in the north to Kyushu island (33-34”N) in the south. A final conclusion concerning latitude dependence in Japan, however, must await proper epidemiological investigation from north to south. In the demographic and clinical features of Japanese patients there was a fair degree of similarity between males and females in terms of the duration of episodes, subtypes of depression, family history and depressive symptoms. However, differences between males and females, although not statistically significant, were observed in other characteristics. Increased appetite and carbohydrate craving were observed more frequently in females than in males. This fact raises the possibility that symptoms related to appetite, which have been considered to be characteristic of SAD, may be specific only for females. Psychomotor activity seemed to be more severely disturbed than affect in both sexes in Japanese SAD, since at the first interview more than 80% of patients showed decreased energy, difficulty in work and interpersonal relationships, whereas only half of the patients showed sadness, irritability or anxiety. A comparison of our results with those of the six previous reports (Rosenthal et al., 1987; Thompson and Isaacs, 1988; Boyce and Parker, 1988; Hellekson, 1989; Wirz-Justice et al., 1989; Terman et al., 1989a) is shown in Table 5. Although there was a fair degree of agreement between the samples in terms of excess of females, age, age at onset, duration of the episodes and previous treatment, considerable differences were seen in sex ratio, number of episodes, lifetime diagnosis and vegetative symptoms. One of our most prominent results is the relatively high percentage of male patients. Previous reports from abroad showed that female patients outnumber males by 3 : 1 or more;while in our study the ratio was only 1.4 : 1. Although a clear explanation of this difference is not readily available, two possibilities can be con-
TABLE 6 THE FEMALE TO MALE RATIO IN THE VARIOUS STAGES OF RECRUITMENT VIA THE MASS MEDIA
Request for questionnaire Questionnaire returned Referral Interview SAD identified
Male
Female
Ratio (Female/ Male)
289 102 37 17 10
815 289 104 33 15
2.82 2.83 2.81 1.94 1 so
sidered. One is a racial difference, i.e., Japanese or Oriental males could be more sensitive to changes in photoperiod than Caucasian males. Another explanation is suggested by the fact that the sex ratio changed during the process of recruitment of patients through the mass media, as shown in Table 6. The ratio was 1 : 2.8 when the patients were screened by questionnaire, consistent with the idea that an annually recurring depression in autumn and winter may be frequent in females. However, the ratio of females to males decreased after the suspected patients were referred to the study facility. This change might suggest that Japanese female patients are hesitant to consult a psychiatrist. It has been said that in American male patients are more hesitant to report depression, for purely sociological reasons (Terman, 1988). Accordingly, the differences in the sex ratio between Western countries and ours could be explained by cultural differences in attitudes to psychiatric disorders. Thus, it might be possible that female patients are underestimated in the present results, while the number of female patients has been overestimated in Western countries. The high percentage of unipolar cases among our patients seems to disagree with the five earlier reports (Rosenthal et al., 1984, 1987; Wirz-Justice et al., 1986; Thompson and Isaacs, 1988; Hellekson, 1989) as .these groups reported that more than 50% of SAD patients were bipolar, while our figure was less than 40%. On the other hand, Terman et al. (1989a) reported a high proportion of unipolar patients (76%). Wirz-Justice et al. (1989) also noted that 90% of their patients were unipolar and neurotic depressives and bipolars were less than 10% in their follow-up study. This
64
considerable variation in the proportion of bipolar patients may be due to problematic diagnostic criteria for bipolarity. Thus, a final conclusion must wait until a sufficient number of patients have been studied in a large number of centers using uniform criteria. Vegetative symptoms, involving increased appetite and carbohydrate craving, are the least frequent in our patients among those reported by previous investigators. This might be due to the relatively high proportion of male patients in our group. A similar trend was also observed with increased weight. On the other hand, an increase in sleep was observed universally in all research groups. In both male and female patients, more than half had mood disorders, including SAD, in first-degree relatives, suggesting that some genetic factors may be involved in Japanese SAD. A high percentage of mental disorders in the family history of SAD patients has also been reported by other authors (Rosenthal et al., 1987; Wirz-Justice et al., 1989; Thompson and Isaacs, 1988; Hellekson, 1989). Based on the general impression of the participating researchers, more than 80% of our patients benefited from light therapy. On the other hand, only 47.4% of patients (nine out of 19 cases) were judged to have remitted when we evaluated the efficacy of light therapy according to the dual criteria applied in the cross-center study of Terman et al. (1989) (HAM-D score reduction of at least 50% and a post-treatment score < 8). However, this conservative estimate of the rate of treatment success still seems to be nearly equal to the 53% (ranging from 41% to 83%) reported for morning light in that Western cross-center study. More recently Stinson and Thompson (1990), studying the largest number of patients in an individual light therapy study reported, demonstrated a remission rate of 43% during a week of light therapy. In the majority of our patients, the light therapy was not discontinued until spring. In no case examined did discontinuation of light exposure change mood. Although we did not compare the two different light sources, full-spectrum fluorescent light and cool-white light, it seems obvious that cool-white fluorescent light is sufficiently effective for the treatment of SAD. This result confirms previous
findings that two different light sources have been equally effective (Lewy et al., 1987; Lebeque and Brown, 1989). The present study demonstrates that light therapy is probably effective for Japanese SAD patients, and that there is no difference between the sexes in degree of effectiveness. However, we have to be cautious in this conclusion in view of the small number of patients and the lack of a control study with dim light or light withdrawal. The underlying pathophysiology of SAD is still unknown, although it is under active investigation as mentioned in a review (Skwerer et al., 1988; Blehar and Rosenthal, 1989; Wehr and Rosenthal, 1989). The large group of SAD patients that are expected to be identified in the multi-center study in Japan will provide an opportunity for further study of the pathophysiology of SAD. Acknowledgements The authors are very grateful to Drs. A. WirzJustice and T.A. Wehr for reviewing the manuscript and providing useful suggestions. The invaluable comments of Dr. M. Terman are also highly appreciated. The present study was supported in part by a Grant-in-Aid for Co-operative Research from the Ministry of Education, Science and Culture of Japan. References Blehar, M.C. and Rosenthal. N.E. (1989) Seasonal affective disorders and phototherapy, report of a National Institute of Mental Health-sponsored workshop. Arch. Gen. Psychiatry 46,469-4X. Boyce, P. and Parker, G. (1988) Seasonal affective disorder in the Southern Hemisphere. Am. J. Psychiatry 145, 96-99. Hellekson. C.J. (1989) Phenomenology of seasonal affective disorder: An Alaskan perspective. In: NE. Rosenthal and M.C. Blehar (Eds.), Seasonal Affective Disorders and Phototherapy. Guilford Press. New York, NY, pp. 33-45. Hellekson. C.J.. Kline, J.A. and Rosenthal, N.E. (1986) Phototherapy for seasonal affective disorder in Alaska. Am. J. Psychiatry 143. 1035-1037. Jacobson, F.M.. Wehr, T.A., Skwerer, R.A., Sack. D. and Rosenthal, N.E. (1987) Morning versus midday phototherapy of seasonal affective disorder. Am. J. Psychiatry 144, 1301-1305. James, S.P., Wehr, T.A., Sack, D.A., Parry, B.L. and Rosenthal, N.E. (1985) Treatment of seasonal affective disorder with evening light. Br. J. Psychiatry 147. 424-428.
65 Lebeque, B. and Brown, J.L. (1989) Morning full spectrum vs cool white light in seasonal affective disorder. Annual Meeting of the Society for Light Treatment and Biological Rhythms, NIH, Bethesda, MD, June 21. Lewy, A.J., Kern, H.E., Rosenthal, N.E. and Wehr, T.A. (1982) Bright artificial light treatment of a manic-depressive patient with a seasonal mood cycle. Am. J. Psychiatry 139, 1496-1498. Lewy, A.J., Sack, R.L., Miller, S. and Hoban, T.M. (1987) Antidepressant and circadian phase-shifting effects of light. Science 235, 352-354. Rosenthal, N.E. and Wehr, T.A. (1987) Seasonal affective disorders. Psychiatr. Ann. 17, 670-674. Rosenthal, N.E., Sack, D.A., Gillin, J.C., Lewy, A.J., Good&, F.K., Davenport, Y., Mueller, P.S., Newsome, D.A. and Wehr, T.A. (1984) Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch. Gen. Psychiatry 41, 72-80. Rosenthal. N.E., Sack, D.A., Carpenter, C.J., Parry, B.L., Mendelson. W-B., Tamarkin, L. and Wehr, T.A. (1985) Antidepressant effects of light in seasonal affective disorder. Am. J. Psychiatry 142, 163-170. Rosenthal, N.E., Targum, S.D., Docherty, T.P., Hoffmann, H.A., Hamovit, J.R., Bryant, M.J. and Kasper, S.F. (1988) Prevalence of SAD and S-SAD by latitude in continental United States. Paper presented at American Psychiatric Association Meeting, Montreal. Skwerer, R.G., Jacobson, F.M., Duncan, C.C., Kelly, K.A., Sack, D.A., Tamarkin, L., Gaist, P.A., Kasper, S. and Rosenthal, N.E. (1988) Neurobiology of seasonal affective disorder and phototherapy. J. Biol. Rhythms 3, 135-154.
Stinson, D. and Thompson, C. (1990) Clinical experience with phototherapy. J. Affect. Disord. 18, 129-135. Terman, M. (1988) On the question of mechanism in phototherapy for seasonal affective disorder: considerations of clinical efficacy and epidemiology. J. Biol. Rhythms 3, 155-172. Terman, M., Botticelli, S.R., Link, B.G., Quitkin, F.M., Hardin, T.E. and Rosenthal, N.E. (1989a) Seasonal symptom pattern in New York: patients and population. In: C. Thompson and T. Silverstone (Eds.), Seasonal Affective Disorder. CNS Publishers, London, pp. 77-95. Terman, M., Terman, J.S., Quitkin, F.M., McGrath, P.J., Stewart, J.W. and Rafferty, B. (1989b) Light therapy for seasonal affective disorder: a review of efficacy. Neuropsychopharmacology 2, l-22. Thompson, C. and Isaacs, C. (1988) Seasonal affective disorder - a British sample: symptomatology in relation to mode of referral and diagnostic subtype. J. Affect. Disord. 14, l-11. Wehr, T.A. and Rosenthal. N.E. (1989) Seasonality and affective illness. Am. J. Psychiatry 146, 829-839. Wirz-Justice, A., Buchelic, C., Graw, P., Kielholz, P., Fisch, H.-U. and Woggon, B. (1986) Light treatment of seasonal affective disorder in Switzerland. Acta Psychiatr. Stand. 74, 193-204. Wirz-Justice, A., Graw, P., Bucheli, C., Schmid, A.C., Gisin, B., Jochum. A. and Poldinoer, W. (1989) Seasonal affective disorder in Switzerland: a clinical perspective. In: C. Thompson and T. Silverstone (Eds.). Seasonal Affective Disorder. CNS Publishers, London, pp. 69-76.
57 Division)
0165-0327/91/$03.50
JAD 00772
Multi-center
study of seasonal affective disorders A preliminary report
in Japan.
K. Takahashi I, Y. Asano 2, M. Kohsaka 3, M. Okawa 4, M. Sasaki 5, Y. Honda 6, T. Higuchi ‘, J. Yamazaki *, Y. Ishizuka 9, K. Kawaguchi lo, T. Ohta “, K. Hanada 12, Y. Sugita 13, K. Maeda 14, H. Nagayama 15, T. Kotorii 18, K. Egashira I7 and S. Takahashi I2 ’ Division of Mental Disorders Research, National Institute of Neurosciences. NCNP, Kodaira. ’ Shukutsu Mental Hospital, Muroran. Departments of Psychtatty of s Hokkaido University, Sapporo, 4 Akita University, Akita. 5 Jtkei Unwerstty, Tokyo. e Seiwa Hospital, Neuropsychiatric Research Instrtute, Tokyo, Departments of Psychiatry OJ 7 Gunma University, Maebashi, a Saitama Medical School, More, 9 Yamanashi Medical College, Kofu, to Hamamatsu University, Hamamatsu, t’ Nagoya University, Nagoya, ” Shiga University of Medical Science, Otsu, ” Osaka Unioersity, Osaka I4 Kobe University, Kobe, ‘-s Medtcal College of Otto. Oita, t6 Kurume University, Kurume and ” University oj Occupational and Envtronmental Health, Kitakyushu. Japan (Received 26 February 1990) (Accepted 3 October 1990)
Summary A multi-center study on seasonal affective disorder (SAD) was conducted from the autumn of 1988 to the spring of 1989 with the cooperation of 16 facilities in Japan. Forty-six SAD patients were identified among 1104 respondents to our advertisements in mass media, or patients seen at the outpatient clinics. Essentially similar findings to other previous reports were obtained in terms of onset age of the first episode, duration of episode, high proportion of depression in first-degree relatives and atypical vegetative symptoms. However, a nearly equal sex ratio, together with a high proportion of unipolar depression, is characteristic of the present study. Increased appetite and carbohydrate craving were predominant only in female patients, whereas hypersomnia was prominent in both sexes. Effective response to light therapy was found in 17 SAD patients. However, a controlled study on a large number of patients is required to allow final conclusions on the efficacy of light therapy in Japanese SAD patients.
Key words:
Seasonal
affective
disorder;
Phototherapy;
Demographic
features;
Clinical
features
Introduction Address for correspondence: Kiyohisa Takahashi, M.D., Division of Mental Disorders Research, National Institute of Neurosciences, NCNP, 4-l-l Ogawahigashi. Kodaira-City, Tokyo 187, Japan.
During the past 5 years a number of research groups in North America, Europe and the South-
58
em hemisphere have reported on seasonal affective disorder (SAD). It has been demonstrated that these disorders have characteristic backgrounds and symptoms. In particular, a high incidence of female patients has been consistently ‘observed in all the studies reported. Moreover, familial loading for affective disorder is also suggested. As to symptoms, several atypical vegetative symptoms have been reported, such as hyperphagia, hypersomnia, weight gain and/or carbohydrate craving. The depressive state has been reported to be ameliorated by bright light exposure for at least 1-2 h/day. This fact has led to speculations that the psychopathological mechanism underlying the disorder may be related to photoperiodism or the phase of the circadian rhythms (Lewy et al., 1982; Rosenthal et al., 1984; James et al., 1985; Wirz-Justice et al., 1986; Hellekson et al., 1986; Jacobsen et al., 1987; Terman, 1988; Thompson and Isaacs, 1988; Boyce and Parker, 1988). It would be of interest to investigate whether Orientals are as sensitive to seasonal changes in light as Caucasians. To our knowledge no systematic study of SAD in Orientals has been reported. As there is a marked difference in skin pigmentation between the two races, it would be reasonable to conceive that this difference might be associated with differences in symptoms or incidence of SAD. With these considerations in mind, members of the Japanese research group on chronobiology, which was organized in 1986, started a multi-center survey of SAD in Japan in autumn 1988 with the support of a Research Grant from the Ministry of Education, Science and Culture (the representative of this research group is S. Takahashi). We recruited SAD patients with the help of the news media as in previous studies (Rosenthal et al., 1984; Wirz-Justice et al., 1986; Thompson and Isaacs, 1988) to investigate whether or not a group of SAD patients also exists in our country. Further, we administered light therapy to a limited number of patients, to determine whether Japanese patients might also respond to bright light. We here report the preliminary results obtained in the first year of the project between the autumn of 1988 and the spring of 1989.
Methods Recruitment of patients Patients were recruited in two different ways: first by identification of SAD in each outpatient clinic of the facilities involved in the project, and second by recruitment through nationwide or local newspapers. After publication of a scientific article describing Rosenthal’s operational criteria for SAD and SAD symptoms including specific vegetative symptoms, such as increased appetite and increased sleep, 1104 people requested questionnaires. The Japanese questionnaire, which was a modified version of the Seasonal Screening Questionnaire (SSQ) devised by Rosenthal et al. (personal communication), was sent to the respondents. When the answers to the questionnaire met the following criteria, prospective patients were referred to the nearest study facility, where they were interviewed to obtain details of their history and symptoms. (1) All depressive episodes occurred in autumn or winter. (2) At least two depressive episodes were observed in two consecutive years. (3) No depressed state was suggested during spring and summer. (4) Depression as stated by the respondents seemed to be so severe as to meet the criteria of major depression in DSM-IIIR. (5) Depressed states seemed not to be caused by any evident psychological events. In the interview onset time of each depressive episode was particularly investigated as precisely as possible to determine the variation of onset time in individuals. We have followed Rosenthal’s operational criteria for the diagnosis of SAD (1984), using DSM-IIIR criteria to evaluate major depressive episodes instead of the RDC, because the DSM-III is much more widely used in our countryThe Schedule for Affective Disorders and Schizophrenia was not systematically used. Instead, we have used DSM-IIIR to make the diagnosis bipolar or unipolar with or without hypomanic episodes. We took it for granted that these three groups correspond to RDC bipolar I, bipolar II and unipolar and compared our data with those reported by others.
Light therapy Informed consent was obtained from the patients who agreed to participate in the light therapy study. As the number of light boxes available was limited, only 17 patients underwent light therapy (10 males and seven females). Thirteen patients were inpatients, while four patients were treated in their own homes. The present pilot study was an open trial to see if phototherapy is effective in Japanese SAD patients. We therefore investigated the effect of dim light or light withdrawal as a control study in only a few cases. In the standard light therapy procedure, the patients were exposed to a light intensity of 25003000 lux for 2 h in the morning, usually between 06.00 h and 08.00 h. We adopted this light intensity, because previous papers have reported success with it in achieving an antidepressant effect. The time of day of the light exposure was also decided on the basis of previous reports (Terman et al., 1989a). The light source consisted of 12 X 20 W cool-white fluorescent tubes. Patients were instructed to sit 1 m away from the light source and to look into the light at least once a minute. As a rule, evaluation according to the Hamilton Rating Scale for Depression (HAM-D) was done by a participating researcher in the morning 1-2 days before and 1-2 weeks after the start of light therapy. The minimum entry criterion for the therapy was a HAM-D score of 10. We compared the male and female groups of our study statistically with the &i-square test. We also compared our data with those of other researchers outside Japan, using the same method. Results Clinical and demographic features of SAD in Japan Eventually 46 SAD patients were identified, 21 in the outpatient clinic and 25 via mass media recruitment. In the latter case 141 suspected cases were screened, based on the answers to the questionnaire, and referred to participating researchers. However, only 50 persons visited the facility to be interviewed. All 46 patients, 19 males and 27 females, fulfilled DSM-IIIR criteria for a history of major depressive episodes. The main reasons for exclusion after the interview were an obvious effect of
TABLE
1
WIDTH OF TEMPORAL ONSET OF THE EPISODES
WINDOW IN EACH
COVERING PATIENT
Male
Female
Total
60 days 90 days
10 (8) 6 (4)
9 (8) 6 (6)
19 (16) 12 (10)
120 days 150 days 180 days
2 (2) l(1) 0 (0)
8 (7) 3 (3) l(1)
10 (9) 4 (4) 1 (1)
Numbers episodes.
in parentheses
show patients
with more
than
THE
three
psychosocial stressors, equivocal seasonality, and lack of symptoms meeting DSM-IIIR criteria for major depression. The variation of onset time of depressive episodes in individuals is shown in Table 1. Two thirds (67%) of SAD patients manifested symptoms within a period of 90 days between September and February, the period being specific to each patient. When the window was narrowed to 60 days for each patient, as required by the definition in DSM-IIIR, the percentage decreased to 41. As shown in Table 2, SAD patients were identified all over the Japanese archipelago, from Hokkaido to Kyushu, with a latitude range of 33-42O. In the study facilities in the south (33-34” N) and the north (42-43 o N) equal numbers of SAD patients were observed. Demographic and clinical features are shown in Table 3. Although female
TABLE
2
RELATIONSHIP OF PATIENTS
BETWEEN IDENTIFIED
LATITUDE AND NUMBERS IN THE PRESENT STUDY
Latitude
City
Males
Females
(ON) 5 3
Sapporo, Muroran Akita Tokyo, Moro, Kofu. Shizuoka, Nagoya, Otsu
42-43 39.5
2 (1) 2
35-36
8 (7)
12 (11)
Osaka Kitakyushu, Ohita
34.5
5 (3)
3 (2)
2 19 (15)
4 27 (25)
Numbers episodes.
Kurume, 33-34
in parentheses
show patients
with more
than
three
TABLE
3
CLINICAL AND DEMOGRAPHIC TIENTS WITH SAD Males Number Age + SEM Age at onset (years) Number of episodes Duration of episodes Mental disorders observed SAD Affective disorder Schizophrenia Alcoholism Others
FEATURE
Females
19 35.4i 22.9 i 9.3 + 4.6 *
3.7 3.4 2.5 0.3
27 35.7 28.6 4.8 4.3
+ + f f
OF
PA-
Total 46 35.5 f 2.2 26.5 f 1.9 6.5*1.1 4.4 + 0.2
2.4 2.4 0.4 0.3
in first-degree relatives 0% 16% 53% 40% 7% 5% 7% 16% 7% 8%
10% 45% 8% 13% 8%
RDC diagnosis Bipolar I Bipolar II Unipolar
6.7% 33.3% 60.0%
10.0% 25.0% 65.0%
8.6% 28.6% 62.9%
Affect Sadness Irritability Anxiety
80% (50%) 67% (56%) 93% (53%)
80% (44%) 84% (59%) 92% (48%)
80% (47%) 78% (58%) 93% (50%)
Psychomotor depression Reduced activity Difficulty in work Reduced social function Appetite Increased Decreased Unchanged Carbohydrate
craving
Weight Increased Decreased Unchanged Sleep Increased Sleepiness daytime Numbers observed
100% (85%) 100% (93%) 100% (91%) 100% (80%) 100% (82%) 100% (81%) 100% (90%) 100% (85%) 100% (87%)
22% 22% 41% 35%
56% 24% 21% 78%
42% 23% 28% 60%
47% 6% 41%
58% 8% 27%
54% 7% 28%
70%
78%
74%
50%
52%
51%
during
in parentheses show at the first interview.
the percentage
of symptoms
patients outnumbered males, the ratio was only 1.4 : 1. Age at the time of entry into the study was 33.2 years in the former and 18-59 in the latter. Both average age of onset and duration of the depressive episodes were almost equal in the two sexes. Similarly, the occurrence of mania or hypomania during spring and summer and a family
history of mood disorder and other psychoses were observed equally in both sexes. According to their life history 8.6% of patients seemed to have experienced a manic episode, while 28.6% could be considered to have had hypomanic episodes. About 60% of patients showed a unipolar pattern. Symptoms related to psychomotor retardation, such as reduced activity, difficulty in work or reduced social activity, were observed in all patients examined during the episode of depression. Similarly a high percentage of changes in affect, such as sadness, irritability or anxiety, was also seen. However, at the entry to the study, a marked difference in the percentage of symptoms was noticed (Table 3). Changes in psychomotor activity were still numerous compared with those in affect. The incidence of overeating (0.05 < P -c 0.1) together with carbohydrate craving (P < 0.05) was higher in females than males, while no sex difference in weight increase was observed. In both sexes more than 70% of patients showed hypersomnia. Light therapy The effect of light therapy on depression is shown in Table 4. The mean percentage reduction in the HAM-D score was 50.8% with no obvious sex differences. Eight of 17 patients (47.4%) were judged to have remitted according to the dual criteria applied in the cross-center study of Terman et al. (1989b) (HAM-D score reduction of at least 50% and a post-treatment score < 8). Seven out of 17 patients (41.2%) did not satisfy both criteria. Based on the general clinical impressions of the participating researchers. although that was an unstructured subjective impression, S/10 (80%) male patients and 6/7 (85.2%) female patients benefited from light therapy. None of the patients complained of any physical trouble caused by the light therapy. Ophthalmological examination also revealed no side effects of light therapy. Discussion The present preliminary study demonstrated that SAD - a syndrome of major depression recurring annually in autumn and winter - exists over all the Japanese islands and that light therapy seems to be effective in the treatment of the
61 TABLE 4 EFFECT
OF LIGHT THERAPY Pre HAM-D
Males
Difference
Reduction rate
Physicians’ evaluation TC
GI
11 4 4 4 14 14
7 7 11 6 B 0
38.9 63.6 73.3 60.0 36.4 0.0
++ ++ ++ -
++ ++ ++ ++ + -
15 25 16 11
5 12 4 8
10 13 12 3
66.7 52.0 75.0 27.3
++ + ++ -
+ + ++ -
++ ++ ++ + -
++ + ++ ++ ++ ++ -
18 12 18 17 23 32 22 (20.2 + 6.3)
Mean
Post HAM-D
18 11 15 10 22 14
(15.7 + 4.9) Females
ON HAM-D
17.6k5.8
(8.0 + 4.3)
(7.7 * 4.1)
2 8 7 12 4 9 20
16 4 11 5 19 23 2
(8.9k5.9)
88.9 33.3 61.1 29.4 82.6 71.9 9.1
(11.758.5)
8.4 i 4.9
(47.9 k 25.3)
9.4 i 6.4
(55.Ok31.7) 50.8 f 27.4
Pre and Post HAM-D show HAM-D evaluated shortly before the start of light therapy and after l-2 weeks of light therapy, respectively. TC represents the results evaluated according to Terman’s criteria (+ + : both > 50% and < 8; + : either > 50% or x 8; - : neither 50% nor < 8). GI represents the global impression of the participating researcher.
disorder. However, further study on light therapy is required to confirm its efficacy, as the number of patients examined was not sufficient and controlled comparisons with dim light or light withdrawal were scarcely performed. For the most part we followed the operational criteria of Rosenthal et al. (1984) concerning timing of the onset of episodes and remission, consecutiveness of episodes, exclusion of an evident relationship with psychosocial events or physical or mental disorders. However, since the DSM-IIIR criteria for major depression were most acceptable to study members, we adopted them instead of RDC to evaluate the depressive state. This choice was also influenced by the introduction of the criteria for a seasonal pattern of mood disorder in DSM-IIIR. As we examined our data on the winter type of seasonal depression, we could not accept DSM-IIIR criteria in their present form. However, we also aimed to evaluate the validity of criteria
dealing with the number of episodes and the duration of the window for episode onsets. In the DSM-IIIR criteria, the window of onset and remission from the depressive episode is set at a particular 60 days of the year in individuals. We therefore examined the variation in onset time of the depressive episode in each patient, as shown in Table 1. Only 41% (or 40%) of all SAD patients examined met the criteria, suggesting that a 60 day window is insufficient to identify the disorder. If we had followed the DSM-IIIR criteria for seasonal pattern strictly, more than half of the SAD patients in Japan would have been overlooked. As to the number of episodes, we found six patients with only two episodes, who did not satisfy the DSM-IIIR criteria. There was, however, no difference in the demographic and clinical features between the patient groups with more than two and three episodes (data not shown). This fact suggests that at least two consecutive episodes in
62 TABLE
5
CHARACTERISTICS
OF A SEASONAL Japan (n=46)
AFFECTIVE U.S.A. ’ (Maryland) (n=246)
Mean age (years) Sex ratio (F : M)
35.5 1.4:1
38 4.6
Depression Mean age at first episode Mean number of episodes Mean duration of episodes
26.5 6.5 2ow
22 -
Affect Sadness Anxiety Irritability Psychomotor depression Reduced activity Reduced social function (difficulty in interpersonal relationship) Work difficulties
:1 * *
DISORDER
GROUP
AND
U.K.’
Switzerland
(n=42)
(n = 63)
(n = 23)
43.8 3.5 : 1 (49 : 14)
_ 6.7
42 9:1**
3
COMPARISONS Australia
:1 +
4
WITH
OTHER
SERIES
U.S.A. 5 (New York) (n =163)
U.S.A. 6 (Alaska) (n=17)
39.3 5.O:l * (136 : 27)
38 15.7:
1* *
31.5 -
23W
24 17 18W
80% 93% 78%
96% 87% 86%
96% 86% 77%
91% = 86% a 82% a
78.3% 82.6% 82.6%
95% 76% 84%
100%
95%
100%
100% L
87.0%
97%
100% 100%
93% 86%
98% 100%
100% a 100% =
95.7% 95.7%
90% 87%
-
2.5% 23.3% 47.2% 27% (Minor)
0% 82% * 18%
47.8% 34.8% 47.8% 30.5% 78.3% 39.1%
77.0% * 9.3% * 77.6% 5.0% 88.2% 71.4%
_
82.6%
6% ** 9% 32% -
33% -
58%
43%
2.5M (23W)
RDC diagnosis Bipolar I Bipolar II Unipolar
8.6% 28.6% 63.8%
7% 81% ** 12% **
18% 37% 45%
Vegetative symptoms Appetite increased Appetite decreased Weight increased Weight decreased Carbohydrate craving Sleep increased
42% 23% 54% 23% 60% 74%
71% * 18% 76% 10% * 72% 83%
74% 16% 84% 6% 82% 78%
45% 45% 55% 23% 77% 82%
Previous treatment Inpatient Lithium Antidepressants Benzodiazepines No treatment
22% 3% 63% 60% 33%
11% 10% 42% -
18% 16% * 49% 40% 51%
8% 12% 66% -
26%
W, weeks, M, months. * P < 0.05, * * P < 0.01 compared with the present data (Japan). References: 1: Rosenthal, 1987 (cited in Hellekson, 1989); 2: Thompson Parker, 1988; 5: Terman et al., 1989; 6: Hellekson, 1989. a Cited from Wire-Justice et al.. 1987.
-
0% = 90% a (8%) 10% a (90%) (Number in parentheses shows percentage according to clinical diagnosis)
= a = = = a
26%
and Isaacs, 1988; 3: Win-Justice
21.1 4.8M (18W)
25 -
-
8%
et al., 1989; 4: Boyce and
63
winter may be sufficient to make the diagnosis of SAD, although admittedly the number of patients in our study was too small to allow a final conclusion. Although a strong latitude dependence of this syndrome has been reported (Rosenthal et al., 1988) the numbers of patients identified in our study were distributed equally from Hokkaido island (42-45 ON) in the north to Kyushu island (33-34”N) in the south. A final conclusion concerning latitude dependence in Japan, however, must await proper epidemiological investigation from north to south. In the demographic and clinical features of Japanese patients there was a fair degree of similarity between males and females in terms of the duration of episodes, subtypes of depression, family history and depressive symptoms. However, differences between males and females, although not statistically significant, were observed in other characteristics. Increased appetite and carbohydrate craving were observed more frequently in females than in males. This fact raises the possibility that symptoms related to appetite, which have been considered to be characteristic of SAD, may be specific only for females. Psychomotor activity seemed to be more severely disturbed than affect in both sexes in Japanese SAD, since at the first interview more than 80% of patients showed decreased energy, difficulty in work and interpersonal relationships, whereas only half of the patients showed sadness, irritability or anxiety. A comparison of our results with those of the six previous reports (Rosenthal et al., 1987; Thompson and Isaacs, 1988; Boyce and Parker, 1988; Hellekson, 1989; Wirz-Justice et al., 1989; Terman et al., 1989a) is shown in Table 5. Although there was a fair degree of agreement between the samples in terms of excess of females, age, age at onset, duration of the episodes and previous treatment, considerable differences were seen in sex ratio, number of episodes, lifetime diagnosis and vegetative symptoms. One of our most prominent results is the relatively high percentage of male patients. Previous reports from abroad showed that female patients outnumber males by 3 : 1 or more;while in our study the ratio was only 1.4 : 1. Although a clear explanation of this difference is not readily available, two possibilities can be con-
TABLE 6 THE FEMALE TO MALE RATIO IN THE VARIOUS STAGES OF RECRUITMENT VIA THE MASS MEDIA
Request for questionnaire Questionnaire returned Referral Interview SAD identified
Male
Female
Ratio (Female/ Male)
289 102 37 17 10
815 289 104 33 15
2.82 2.83 2.81 1.94 1 so
sidered. One is a racial difference, i.e., Japanese or Oriental males could be more sensitive to changes in photoperiod than Caucasian males. Another explanation is suggested by the fact that the sex ratio changed during the process of recruitment of patients through the mass media, as shown in Table 6. The ratio was 1 : 2.8 when the patients were screened by questionnaire, consistent with the idea that an annually recurring depression in autumn and winter may be frequent in females. However, the ratio of females to males decreased after the suspected patients were referred to the study facility. This change might suggest that Japanese female patients are hesitant to consult a psychiatrist. It has been said that in American male patients are more hesitant to report depression, for purely sociological reasons (Terman, 1988). Accordingly, the differences in the sex ratio between Western countries and ours could be explained by cultural differences in attitudes to psychiatric disorders. Thus, it might be possible that female patients are underestimated in the present results, while the number of female patients has been overestimated in Western countries. The high percentage of unipolar cases among our patients seems to disagree with the five earlier reports (Rosenthal et al., 1984, 1987; Wirz-Justice et al., 1986; Thompson and Isaacs, 1988; Hellekson, 1989) as .these groups reported that more than 50% of SAD patients were bipolar, while our figure was less than 40%. On the other hand, Terman et al. (1989a) reported a high proportion of unipolar patients (76%). Wirz-Justice et al. (1989) also noted that 90% of their patients were unipolar and neurotic depressives and bipolars were less than 10% in their follow-up study. This
64
considerable variation in the proportion of bipolar patients may be due to problematic diagnostic criteria for bipolarity. Thus, a final conclusion must wait until a sufficient number of patients have been studied in a large number of centers using uniform criteria. Vegetative symptoms, involving increased appetite and carbohydrate craving, are the least frequent in our patients among those reported by previous investigators. This might be due to the relatively high proportion of male patients in our group. A similar trend was also observed with increased weight. On the other hand, an increase in sleep was observed universally in all research groups. In both male and female patients, more than half had mood disorders, including SAD, in first-degree relatives, suggesting that some genetic factors may be involved in Japanese SAD. A high percentage of mental disorders in the family history of SAD patients has also been reported by other authors (Rosenthal et al., 1987; Wirz-Justice et al., 1989; Thompson and Isaacs, 1988; Hellekson, 1989). Based on the general impression of the participating researchers, more than 80% of our patients benefited from light therapy. On the other hand, only 47.4% of patients (nine out of 19 cases) were judged to have remitted when we evaluated the efficacy of light therapy according to the dual criteria applied in the cross-center study of Terman et al. (1989) (HAM-D score reduction of at least 50% and a post-treatment score < 8). However, this conservative estimate of the rate of treatment success still seems to be nearly equal to the 53% (ranging from 41% to 83%) reported for morning light in that Western cross-center study. More recently Stinson and Thompson (1990), studying the largest number of patients in an individual light therapy study reported, demonstrated a remission rate of 43% during a week of light therapy. In the majority of our patients, the light therapy was not discontinued until spring. In no case examined did discontinuation of light exposure change mood. Although we did not compare the two different light sources, full-spectrum fluorescent light and cool-white light, it seems obvious that cool-white fluorescent light is sufficiently effective for the treatment of SAD. This result confirms previous
findings that two different light sources have been equally effective (Lewy et al., 1987; Lebeque and Brown, 1989). The present study demonstrates that light therapy is probably effective for Japanese SAD patients, and that there is no difference between the sexes in degree of effectiveness. However, we have to be cautious in this conclusion in view of the small number of patients and the lack of a control study with dim light or light withdrawal. The underlying pathophysiology of SAD is still unknown, although it is under active investigation as mentioned in a review (Skwerer et al., 1988; Blehar and Rosenthal, 1989; Wehr and Rosenthal, 1989). The large group of SAD patients that are expected to be identified in the multi-center study in Japan will provide an opportunity for further study of the pathophysiology of SAD. Acknowledgements The authors are very grateful to Drs. A. WirzJustice and T.A. Wehr for reviewing the manuscript and providing useful suggestions. The invaluable comments of Dr. M. Terman are also highly appreciated. The present study was supported in part by a Grant-in-Aid for Co-operative Research from the Ministry of Education, Science and Culture of Japan. References Blehar, M.C. and Rosenthal. N.E. (1989) Seasonal affective disorders and phototherapy, report of a National Institute of Mental Health-sponsored workshop. Arch. Gen. Psychiatry 46,469-4X. Boyce, P. and Parker, G. (1988) Seasonal affective disorder in the Southern Hemisphere. Am. J. Psychiatry 145, 96-99. Hellekson. C.J. (1989) Phenomenology of seasonal affective disorder: An Alaskan perspective. In: NE. Rosenthal and M.C. Blehar (Eds.), Seasonal Affective Disorders and Phototherapy. Guilford Press. New York, NY, pp. 33-45. Hellekson. C.J.. Kline, J.A. and Rosenthal, N.E. (1986) Phototherapy for seasonal affective disorder in Alaska. Am. J. Psychiatry 143. 1035-1037. Jacobson, F.M.. Wehr, T.A., Skwerer, R.A., Sack. D. and Rosenthal, N.E. (1987) Morning versus midday phototherapy of seasonal affective disorder. Am. J. Psychiatry 144, 1301-1305. James, S.P., Wehr, T.A., Sack, D.A., Parry, B.L. and Rosenthal, N.E. (1985) Treatment of seasonal affective disorder with evening light. Br. J. Psychiatry 147. 424-428.
65 Lebeque, B. and Brown, J.L. (1989) Morning full spectrum vs cool white light in seasonal affective disorder. Annual Meeting of the Society for Light Treatment and Biological Rhythms, NIH, Bethesda, MD, June 21. Lewy, A.J., Kern, H.E., Rosenthal, N.E. and Wehr, T.A. (1982) Bright artificial light treatment of a manic-depressive patient with a seasonal mood cycle. Am. J. Psychiatry 139, 1496-1498. Lewy, A.J., Sack, R.L., Miller, S. and Hoban, T.M. (1987) Antidepressant and circadian phase-shifting effects of light. Science 235, 352-354. Rosenthal, N.E. and Wehr, T.A. (1987) Seasonal affective disorders. Psychiatr. Ann. 17, 670-674. Rosenthal, N.E., Sack, D.A., Gillin, J.C., Lewy, A.J., Good&, F.K., Davenport, Y., Mueller, P.S., Newsome, D.A. and Wehr, T.A. (1984) Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch. Gen. Psychiatry 41, 72-80. Rosenthal. N.E., Sack, D.A., Carpenter, C.J., Parry, B.L., Mendelson. W-B., Tamarkin, L. and Wehr, T.A. (1985) Antidepressant effects of light in seasonal affective disorder. Am. J. Psychiatry 142, 163-170. Rosenthal, N.E., Targum, S.D., Docherty, T.P., Hoffmann, H.A., Hamovit, J.R., Bryant, M.J. and Kasper, S.F. (1988) Prevalence of SAD and S-SAD by latitude in continental United States. Paper presented at American Psychiatric Association Meeting, Montreal. Skwerer, R.G., Jacobson, F.M., Duncan, C.C., Kelly, K.A., Sack, D.A., Tamarkin, L., Gaist, P.A., Kasper, S. and Rosenthal, N.E. (1988) Neurobiology of seasonal affective disorder and phototherapy. J. Biol. Rhythms 3, 135-154.
Stinson, D. and Thompson, C. (1990) Clinical experience with phototherapy. J. Affect. Disord. 18, 129-135. Terman, M. (1988) On the question of mechanism in phototherapy for seasonal affective disorder: considerations of clinical efficacy and epidemiology. J. Biol. Rhythms 3, 155-172. Terman, M., Botticelli, S.R., Link, B.G., Quitkin, F.M., Hardin, T.E. and Rosenthal, N.E. (1989a) Seasonal symptom pattern in New York: patients and population. In: C. Thompson and T. Silverstone (Eds.), Seasonal Affective Disorder. CNS Publishers, London, pp. 77-95. Terman, M., Terman, J.S., Quitkin, F.M., McGrath, P.J., Stewart, J.W. and Rafferty, B. (1989b) Light therapy for seasonal affective disorder: a review of efficacy. Neuropsychopharmacology 2, l-22. Thompson, C. and Isaacs, C. (1988) Seasonal affective disorder - a British sample: symptomatology in relation to mode of referral and diagnostic subtype. J. Affect. Disord. 14, l-11. Wehr, T.A. and Rosenthal. N.E. (1989) Seasonality and affective illness. Am. J. Psychiatry 146, 829-839. Wirz-Justice, A., Buchelic, C., Graw, P., Kielholz, P., Fisch, H.-U. and Woggon, B. (1986) Light treatment of seasonal affective disorder in Switzerland. Acta Psychiatr. Stand. 74, 193-204. Wirz-Justice, A., Graw, P., Bucheli, C., Schmid, A.C., Gisin, B., Jochum. A. and Poldinoer, W. (1989) Seasonal affective disorder in Switzerland: a clinical perspective. In: C. Thompson and T. Silverstone (Eds.). Seasonal Affective Disorder. CNS Publishers, London, pp. 69-76.
