Koichi Hanada

Circadian rhythms in depression: Part II: Circadian rhythms in inpatients with various mental disorders

We investigated longitudinally the circadian body temperature rhythms in 65 inpatients with various mental disorders, 38 of whom had major depressive episodes, by estimating the deep body temperature from the skin surface every 2 h for a consecutive 48-h period. To estimate the circadian rhythm, the data obtained were analyzed by the least-squares method and maximum entropy spectral analysis (MEM). Circadian rhythm disturbances in patients with depression were likely to be manifested in phase variability rather than in phase advance. The amplitude of body temperature of the depressed group was significantly less than that of the control group. A positive correlation between the mesor and the severity of the depressive symptoms was found. Moreover, the body temperature of the patients with affective disorders, both in the depressive and in the manic state, tended to fluctuate so much as not only to fit poorly to sinusoid curves, but also to reduce the periodicity of the circadian rhythm. On the basis of these findings, we conclude that the essential feature of the rhythm disturbances in affective disorders is not the phase shift but the instability of the circadian temperature rhythm.

Circadian rhythms in depression: Part I: Monitoring of the circadian body temperature rhythm

In order to develop a sampling strategy and a method for analyzing the circadian body temperature pattern, we monitored estimates of the temperature in four ways using rectal, oral, axillary and deep body temperature from the skin surface every hour for 72 consecutive hours in 10 normal control subjects. Data obtained were analyzed with the least-squares method to estimate the circadian rhythm. Deep body temperature from the skin surface correlated better with rectal temperature than with either oral or axillary temperature in all subjects. The correlation coefficient between rectal and deep body temperature from the skin surface ranged between 0.66 and 0.89. The acrophases calculated from the deep body temperature from the skin surface every 2 h for 48 h were consistent with those based on the rectal temperature every 10 min for 72 h. We believe that monitoring of the deep body temperature from the skin surface, in this manner, at intervals of 2 h for a period of 2 days, is a promising method for investigating circadian body temperature rhythm, because it causes less discomfort than other measures and has greater statistical validity for data computation.

MULTI-CENTER STUDY OF SEASONAL AFFECTIVE DISORDERS IN JAPAN : A PRELIMINARY REPORT

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.

Atypical depressive symptoms possibly predict responsiveness to phototherapy in seasonal affective disorder

Phototherapy was administered to 24 depressed patients with seasonal affective disorder (SAD), of which 62%, 24%, and 14%, respectively, showed improvements of greater than or equal to 50%, 25-50%, and less than 25% based on the Hamilton rating scale for depression for SAD (HAMSAD). No patients showed aggravation or side effects. Although the improvement rate in HAMSAD correlated significantly with the pretreatment severity of atypical symptoms of depression, it did not correlate with that of typical symptoms. This suggests that phototherapy is a useful treatment in SAD and that responsiveness to phototherapy in SAD can possibly be predicted by the atypical depressive symptoms before treatment.

Direct radioimmunoassay of cortisol in saliva and its application to the dexamethasone suppression test in affective disorders

In order to perform the dexamethasone suppression test (DST) with saliva as an alternative to serum, we assayed directly the cortisol concentrations in 25 microliters saliva samples, using a commercial radioimmunoassay kit for serum cortisol with minor modifications. Cortisol in saliva showed a diurnal rhythm parallel to that of cortisol in serum samples collected simultaneously. Saliva cortisol levels increased significantly after ACTH injection, but with a 60 min delay in reaching their peak compared to peak serum cortisol levels. The increase in saliva cortisol was five-fold, while that in serum was two-fold. Saliva cortisol levels continued to increase in some subjects while serum total cortisol levels already had begun to decline. In those subjects, the correlation of saliva with serum cortisol was greater when a quadratic curve was fitted than when calculated for a linear correlation. Considerable variation was observed for within-subject correlations, ranging from + 0.48 to + 0.999. The DST with saliva sample collection was performed on 43 inpatients with affective disorders. Sensitivity, specificity and diagnostic confidence of the DST for major depressive episode with melancholia were 33%, 91%, and 78%, respectively, at the criterion value of 0.3 microgram/100 ml for saliva cortisol, which are similar to those most often reported for the DST with serum cortisol determination. These results indicate that saliva cortisol levels do not always parallel serum cortisol levels and thus are not an unequivocal substitute. The findings for the DST in psychiatric patients, however, support the practical clinical usefulness of saliva cortisol measurements.

Morning and Evening Adrenocortical Responses to ACTH Stimulation in Endogenously Depressed Patients: A Preliminary Report

Abstract: Adrenocortical stimulation with ACTH both in the morning (M‐test) and in the evening (Etest) and the dexamethasone suppression test were carried out in patients suffering from endogenous depression (DEP) and normal controls (NOR). A greater cortisol release in DEP was recognized than in NOR in the M‐test, an earlier peak response of DEP was shown in the M‐test than in the Etest, and a lack of association between hypersecretion of cortisol during depression and cortisol output after ACTH administration was noted. These findings, together with the results of DST, suggest that excessive activity of the hypothalamic‐pituitary‐adrenal (HPA) axis in depression may result, partly, from adrenocortical hyperresponsiveness.

Dissociation between plasma bioactive and immunoactive ACTH concentrations in depressed patients

Previous studies have reported dissociations between plasma cortisol and immunoactive adrenocorticotropic hormone (ACTH) concentrations in both normal controls and in patients with major depression. In order to investigate this issue further, placebo and dexamethasone (DEX) were administered to normal controls and depressed patients at 11 PM, and plasma cortisol and ACTH were measured the following morning at 7 AM. Plasma ACTH concentrations were quantitated by both immunoassay (I-ACTH) and by bioassay (B-ACTH). In 10 normal controls, DEX (0.25, 0.5, and 1.0 mg, PO, elixir) produced a dose-related suppression of cortisol, I-ACTH and B-ACTH, with all three hormones significantly suppressed by DEX (0.5 and 1.0 mg) (p < or = 0.01). In 20 depressed patients, 7 AM plasma ACTH and cortisol concentrations were assessed following a single dose of DEX (0.5 mg). Fifteen patients were classified as suppressors and five as escapers, as reflected by mean (+/- SEM) cortisol concentration of 19.9 +/- 3.0 ng/ml and 81.2 +/- 7.0 ng/ml, respectively. Mean I-ACTH concentrations were comparable in both the escapers (8.6 +/- 1.6 pg/ml) and in the suppressors (7.0 +/- 1.0 pg/ml). In contrast, the mean B-ACTH concentration was more than two-fold higher in the escapers (4.5 +/- 0.5 pg/ml) than in the suppressors (2.2 +/- 0.3 pg/ml) (p < or = 0.001). Eleven of the 20 patients received both placebo and DEX (0.5 mg) on two separate occasions. Although DEX significantly suppressed both cortisol (p < or = 0.0001) and B-ACTH (p < or = 0.01) concentrations, I-ACTH was not significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Phototherapy on Circadian Rhythms of Body Temperature in Affective Disorders

It has been well established that bright light is capable of ameliorating symptoms in patients with seasonal affective disorder (SAD). However, the intensity and timing of light exposure are controversial. Some researchers pointed out the difference in therapeutic efficacy depending on the differences in timing of light exposure; morning light was more effective than evening light. Some reported that both dim light and bright light were effective, while others reported that dim light was not effective. Therapeutic effects of phototherapy on nonSAD patients are still controversial. Therefore, we conducted an experiment using bright or dim light exposure on non-SAD patients in different timing, that is, in the morning or evening.

Subclassification of Major Affective Disorders and the Risk of Rapid Transition to Mania

Forty-two clinically diagnosed schizophrenic patients were re-diagnosed by Bleuler’s 4A, Schneider’s FRS, ICD-9, DSM-111, Research Diagnostic Criteria and St. Louis criteria. Defining schizophrenia by the presence of at least one of the 4A allocates the largest number of patients (36 cases), while St. Louis criteria attribute only 13 cases to the diagnosis of schizophrenia. All the criteria diagnosed 6 cases as schizophrenia, but 2 cases are diagnosed by none of them. There are different overlapping patterns among the criteria. Three groups are separated by using the cluster analysis. Almost all of the criteria attribute the cases to one group (concordant group, N = 17), and most of them don’t allocate the cases to another group (undiagnosed group, N = 14), and discordance among the diagnoses is seen in the third group (discordant group, N = 11). In the concordant group, “restlessness” and ”lack of concentration,” as well as “any delusion,” “any hallucination” and 7 items in FRS, are observed more frequently than in the other groups (p < .05). The discordant group shows the same pattern of symptom set, but the presence rate is less than the concordant group, while the undiagnosed group shows a different pattern, less auditory hallucination, delusion, and more depressive episodes. A Forensic-Psychiatric Case Showing Symptoms of So-called Atypical Psyehosis