Psychiatry and Clinical Neurosciences (2000), 54, 356–358

Circadian Rhythm

Predisposing factors in delayed sleep phase syndrome YASURO TAKAHASHI, md, phd,1 HIROHIKO HOHJOH, phd2 AND KEIKO MATSUURA, ba1 1

Sleep Disorders Clinic, Seiwa Hospital, Neuropsychiatric Research Institute and 2Department of Human Genetics, Graduate School of Medicine, University of Tokyo,Tokyo, Japan

Abstract

We classified 64 patients with chronic delayed sleep phase syndrome (DSPS) into the primary (n = 53) and secondary (n = 11) group according to presence or absence of such signs as difficulty in waking up which appeared much earlier than the onset of DSPS. The age at the onset of the early signs concentrated in adolescence. The familial occurrence of DSPS was noted in 11 patients of the primary group. In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. Minnesota Multiphasic Personality Inventory revealed high scores on depression, psychoasthenia and hypochondriasis. We suggest that a predisposition to DSPS includes biological, genetic, social and psychological factors, various combinations of which may lead to DSPS.

Key words

delayed sleep phase syndrome, early signs, familial occurrence, HLA-DR1, MMPI, predisposition.

INTRODUCTION Delayed sleep phase syndrome is a circadian rhythm sleep disorder, in which the major sleep episode is so much delayed in relation to the desired clock time that it results in difficulty in adjusting the patient’s sleep onset and wake-up times to school, occupational and social activities. The purpose of the present study is to analyze factors affecting the onset of DSPS from various aspects.

waking up and sitting up late at night persistently emerged several years or much earlier than the onset of DSPS, we termed them the early signs of DSPS. According to whether the early signs were present or not, we classified the DSPS patients into the primary and secondary type, respectively. The 64 patients consisted of 53 patients of the primary type (82.8%) and 11 patients of the secondary type (17.2%). We administered human leukocyte antigen (HLA) typing and Minnesota Multiphasic Personality Inventory (MMPI) to a majority of these patients.

MATERIALS AND METHODS Based on sleep–wake history, sleep logs and follow up, we selected 64 patients with DSPS (46 males and 18 females) from outpatients (1993–99) at our sleep disorders clinic. These patients fulfilled the diagnostic criteria of chronic DSPS defined in International Classification of Sleep Disorders,1 but did not include DSPS patients associated with schizophrenia or major depression. We defined the age at the onset of DSPS as when a patient’s social maladjustment due to DSPS began to be serious to such an extent as frequent lateness and absence, and eventual withdrawal from job or school. When such signs as difficulty in morning

Correspondence address: Yasuro Takahashi, 2-4-16 Kamisaginomiya, Nakano-ku, Tokyo 165-0031, Japan.

RESULTS Ages at the onset of delayed sleep phase syndrome and the early signs The overall mean (± SD) age at the onset of DSPS was 21.2 ± 6.6 years ranging from 12 to 49 years. The mean age at the onset of DSPS was 20.8 ± 5.5 years ranging from 13 to 37 years in the primary group, while it was 23.1 ± 10.4 years ranging from 12 to 49 years in the secondary group. The mean age of onset was not significantly different between the primary and secondary group, but the age distribution was more diffuse in the secondary group. In the primary group, the mean age at the onset of the early signs was 12.4 ± 2.8 years ranging from 6 to 19 years, and the age coincided with adolescence (9 to 14 years) in 41 patients (77.4%).

Predisposition to DSPS

Precipitating factors for the onset of delayed sleep phase syndrome In the primary group, 23 patients had an insidious onset of DSPS. We could not find any particular events precipitating the onset of DSPS, and their tendency toward DSPS gradually increased and led to serious maladjustment. In the remaining 30 patients, the onset of DSPS was associated with one or more of the following factors: difficulties in personal relations, discontent with job or school, new employment, occupational change, shift work, overtime work, irregular sleep habits, insomnia associated with atopic dermatitis or asthma etc. In the secondary group without the early signs, DSPS developed following the precipitating factors that were common to those in the primary group.

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the MMPI profiles of the remaining 39 patients (25 males and 14 females), the number of patients with high scores (T  70) over the normal range was 14, 14, and 13 on the depression, psychoasthenia, and hypochondriasis scale, respectively. Thirteen patients showed low scores (T  45) on the hypomania scale.

Psychosomatic symptoms Thirty-five (54.7%) of the 64 patients often complained of a variety of symptoms, such as fatigue, headache, slight fever, orthostatic hypotension, diarrhea, constipation, chilly constitution and Raynaud phenomenon, most of which were suggestive of autonomic imbalance.

DISCUSSION HLA-DR1 positivity2 We administered the HLA-A, -B, and -DR typing to 56 patients with DSPS and made a statistical comparison of the frequency of antigens to 32 alleles between the 56 patients and 117 healthy subjects. The frequency of HLA-DR1 positivity alone was significantly (P < 0.01, c2-test) higher in the DSPS patients (14/56, 25.0%) than in the healthy subjects (11/117, 9.4%), although the P value (0.063) corrected for multiple comparisons was slightly over the significant level. We could not find any clinical features by which the HLA-DR1-positive patients are distinguishable from the negative patients. The incidence of HLA-DR1 positivity was not significantly different between the primary and secondary group (12/47 vs 2/9).

Familial occurrence of delayed sleep phase syndrome Eleven (20.8%) of the 53 patients of the primary type had one or more patients with DSPS or its suspects in their parents and siblings, while none of the secondary type had them. However, this difference in the incidence of the familial occurrence of DSPS between the two types was not significant (P = 0.102, Fisher’s exact probability test). There was no significant correlation between the familial occurrence and HLADR1 positivity.

Minnesota Multiphasic Personality Inventory profiles We administered MMPI to 45 patients, and excluded six from further analysis because of low validity. In

In the present study, we defined the onset of DSPS by the degree of patients’ social maladjustment. Then we classified DSPS into the primary and secondary type according to the presence or absence of the early signs of DSPS. Sixty-four percent of all DSPS patients had the early signs that emerged during adolescence. Since a natural differentiation between morning and evening chronotype appears during adolescence, the age at onset of the early signs seems to have a biological background. In half of the primary group, difficulty in morning waking persisted from adolescence and came gradually into a serious maladjustment to social life. These patients seem to have a biological predisposition to DSPS. In the other patients, the onset of DSPS was precipitated by a variety of occupational, interpersonal, psychological, environmental and somatic factors, which were closely related to one another. In some patients with the early signs, DSPS did not become manifest while they worked with volition and interest or on flextime. Thus, the manifestation of DSPS seems to depend also on such psychosocial factors. It is noteworthy that the familial occurrence of DSPS was limited to some patients with early signs. In HLA-types that related to susceptibility to various diseases, the incidence of HLA-DR1 positivity alone was higher in the DSPS patients than in the healthy subjects, although only 25% of the patients examined were HLA-DR1 positive. The familial occurrence and the higher frequency of HLA-DR1 positivity suggest that there are some hereditary factors susceptible to DSPS. The MMPI profiles corresponded well to our clinical impressions; in particular we noted depression in a greater or lesser degree in most of the DSPS patients.

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A majority of the patients complained of various psychosomatic symptoms suggestive of autonomic imbalance. However, it was difficult to distinguish whether the personality traits and the psychosomatic symptoms predisposed to DSPS or were caused by DSPS. We conclude that a predisposition to DSPS includes biological, genetic, social, and psychological factors, various combinations of which may lead to DSPS, and thus DSPS is heterogeneous in etiology.

REFERENCES 1. Diagnostic Classification Steering Committee. Delayed sleep phase syndrome. In: International Classification of Sleep Disorders: Diagnostic and Coding Manual. American Sleep Disorders Association, Rochester, Minnesota, 1990; 128–133. 2. Hohjoh H, Takahashi Y, Hatta Y et al. A possible association of human leucocyte antigen (HLA)-DR1 with delayed sleep phase syndrome. Psychiatry Clin. Neurosci. 1999; 53: 527–529.