Diagnosis of Asperger syndrome
AS subjects (n = 20) were, after informed consent, recruited from the Helsinki Asperger Center, a unit to which patients with a tentative diagnosis of AS are referred from all parts of Finland. Prior to inclusion in the present study participants had the following assessment:
The participant himself/herself had a detailed interview by a clinician familiar with autism spectrum disorders focussing on life-history elements essential for the diagnosis of AS. The mother or other significant relative or family member(s) was interviewed on developmental issues relevant for the diagnosis. All available previous medical records were reviewed including data from well baby clinics and school health especially concerning developmental milestones.
Autism spectrum screening questionnaire (ASSQ) is a continuous measure rating scale validated for screening children with tentative autism spectrum disorder [11]. The questionnaire consists of 27 items about patient's behaviour, each scored from 0 to 2 points (score range 0–54). In children a parent rating cut-off of 19 points identifies correctly 82% of AS-patients [11]. In the present study the mothers or other persons in close contact with the subject in childhood filled in ASSQ concerning the subject's childhood behaviour. Each positive score had to be documented with several examples. In one AS subject there was no competent relative to be interviewed and he filled in the ASSQ by himself.
Wechsler Adult Intelligence scale, revised version (WAIS-R) [12] was assessed in all participants by a psychologist familiar with autism spectrum disorders except in one control and in one patient (both having university degree) who refused.
All these data were critically reviewed in corpore by three authors (PT, TN and LvW). All 20 participants fulfilled the ICD-10 and DSM IV-criteria in childhood. Two persons did not meet the full criteria of AS in adulthood but as their problems were essentially similar to those of other subjects they were included in the study group. Exclusion criteria of DSM-IV were followed. Control group (n = 10) consisted of healthy volunteers assessed with same method as the AS group, with no history of neuropsychiatric disorders according to themselves and to anamnesis obtained from parents.
Participants were medication free (with a minimum interval of two weeks for hypnotics, three months for antidepressant medicines and one year for neuroleptics) except of one 44 years old female who had been using thyroxin substitution since childhood.
Associated conditions
Structured Clinical Interview of Diseases (SCID) for DSM III-R [13] was performed for comorbid axis I diagnoses. Because AS-patients are prone to affective disorders [9, 10] their mood was further explored with the Beck Depression Inventory (BDI) [14] in order to quantitate current depressive symptoms potentially affecting sleep quality. Schizophrenia and other chronic psychotic illness in previous medical records or in SCID-interview were used as exclusion criteria. None of the participants had a diagnosis of alcohol misuse or dependency. The controls had no current axis-I diagnoses assessed with SCID-I.
7 AS subjects were devoid of other axis-I diagnoses besides AS. 13 As subjects met the diagnostic criteria of one or more anxiety disorders, the most prevalent being social phobia (n = 8). 5 AS subjects had mild to moderate depressive disorder and none of them had severe MDD.
Also the Structured Clinical Interview of Axis-II disorders for DSM-III-R (SCID-II) [15] was performed to all participants. 5 AS subjects had Cluster A (paranoid, schizoid, schizotypal) personality disorder, and 3 subjects had cluster B (antisocial, borderline, histrionic, narcissistic) disorder. 13 subjects presented Cluster C (avoidant, dependent, obsessive-compulsive, passive-aggressive) personality disorder. 5 subjects had both cluster A and cluster C personality disorder. Obsessive-compulsive personality disorder (12 subjects) or traits of it (7 subjects) were the most common axis-II disorders. Conversely, 6 subjects did not meet the full diagnostic criteria of any axis-II disorders. 4 out of 7 subjects with no axis-I disorder did not have axis II-disorder according to the diagnostic threshold of axis-II although all subjects displayed single or multiple symptoms of some personality disorders. Control subjects did not have axis-II disorders.
Possible confounding comorbid somatic disease was ruled out by means of clinical examination and by a blood test screening for electrolytes, liver and kidney functions, thyroid hormones, calcium metabolism and head MRI (1.5T), the latter in 17 AS subjects and in 9 controls, which all gave normal results.
In many previous studies on autism spectrum disorders the normality of the control group has been inadequately assessed [16]. In the present study all controls were examined using exactly the same procedures as in the AS group.
Sleep questionnaire
Basic Nordic Sleep Questionnaire (BNSQ) is a quantitative scale for assessment of sleep quality developed by the Scandinavian Sleep Research Society [17] and is widely used in sleep studies published in Nordic countries. It consists of 14 statements assessing the frequency of sleep problems during the past three months with five-point scale. Score range is 14–70; the higher score indicating lower sleep quality. Questions concerning some time values of sleep (e.g. sleep latency) are also included. The items describing frequency and severity of insomnia are reported below. After filling in the BNSQ participants proceeded to follow-up period with sleep diary.
Sleep diary
During the mean period of 6 days (range 5–7 days) participants wrote down the time of retiring to bed in order to sleep, estimated time of falling asleep and awakening in the morning and sleep naps in daytime as well as number and duration of awakenings during night time. Sleep latency was calculated by subtracting the time of falling asleep from time of retiring to bed. Time in bed (TIB) was defined as the time period from retiring to bed in the evening to awakening in the morning, and sleep period as the time from falling asleep to awakening in the morning. Sleep efficiency was defined as a ratio between true sleep (time in bed-sleep latency-duration of awakenings) and time in bed. Subjective quality of each night, sleep was assessed with an arbitrary scale from 4–10 (school grades in Finland) higher numbers indicating better sleep quality. These parameters were calculated for each consecutive night in each participant and then averaged for each subject to enable statistical comparison between individuals. Standard deviation (SD) of each parameter reflects the night-to-night variability and thus the individual SD was pooled up in AS subjects and in controls for comparison. Caffeine, nicotine and alcohol consumption during the study period was registered for each recording day. Participants were advised to lead their normal life at home, work or studies during the study period.
One AS subjects was not able to assess the time of falling asleep and two AS subjects could not assess the quality of sleep in consecutive nights. In one control subject the sleep diary data was entirely lacking.
Sleep naps in daytime were a rare event during the study period; In the AS group four subjects reported one sleep nap each and one subject two sleep naps during the study period. Three of the controls reported one sleep nap each.
During the study period 3 AS subjects and 1 control smoked 5 cigarettes or more per day. 3 AS subjects and 1 control had one or two nights with alcohol use more than 24 g per evening. 2 AS subjects (and none of the controls) had both daily smoking and occasional alcohol use. 1 AS subject and 1 control reported excessive use of coffee (more than three cups per day).
Free description
After filling in the BNSQ and during study period all participants were requested to give a detailed description of possible subjective sleep problems as a short essay.
Definition of insomnia
In BNSQ insomnia was defined as follows: difficulty in falling asleep (initial insomnia) as difficulties in falling asleep on 3–5 days per week or more often and/or sleep latency 30 minutes or more (item 1, grade 4–5, item 2a–2b sleep latency ≥ 30 min), difficulty in staying asleep (middle insomnia) as at least 3 awakenings per night (item 4, grade 4–5) and nonrestorative sleep (terminal insomnia) as excessive sleepiness in the morning after awakening or during daytime on 3–5 days per week or more often (item 8 and 9, grade 4–5).
In sleep diary sleep latency and/or wake after sleep onset ≥ 30 minutes or sleep efficiency below 85% defined insomnia. Both the BNSQ and sleep diary criteria were modified according to previously published operational criteria [18].
In free description participants were encouraged to describe the symptoms of poor sleep, which they found to be most disturbing.
Statistics
In BNSQ the items scored with five-point scale display a rank order quality. Therefore the comparison between AS subjects and controls was performed with Mann-Whitney rank sum test. Variability of items was described with range of 25%-75% percentiles. Time values in BNSQ are continuous measures. Therefore the comparison between AS subjects and controls was performed with Student's t-test except in cases where the items studied had a non-normal distribution. In these cases the Mann-Whitney rank sum test was applied.
In the averaged sleep diary items (with continuous measures) the comparison between AS subjects and controls was performed either with Student's t-test or with Mann-Whitney rank sum test depending on whether the parameter studied displayed a normal or non-normal distribution. Fisher exact test was used when comparing the number of subjects with or without insomnia studied with different methods.
Statistical analyses were calculated with commercial computer software (Sigma Stat 2.03, SPSS Inc. 1995).
Ethics
The local ethical committee approved the study and principles of declaration of Helsinki were adequately followed.