Psychiatry Research 152 (2007) 29 35

www.elsevier.com/locate/psychres

Sleep onset REM periods in obsessive compulsive disorder

Michael Kluge , Petra Schssler, Martin Dresler, Alexander Yassouridis, Axel Steiger
Max Planck Institute of Psychiatry, Munich, Germany
Received 7 November 2005; received in revised form 14 February 2006; accepted 4 April 2006

Abstract

Sleep studies in patients with obsessive compulsive disorder (OCD) are sparse and results inconsistent. Moreover, in 3 out of 4
published studies up to 50% of patients suffered from secondary major depression. In this study, 10 inpatients with a DSM-IV
diagnosis of OCD without comorbid major depression (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score N15; Hamilton
Depression Rating Scale (HAMD)-21 total score b 17) and 10 healthy matched controls were included. Polysomnography of
patients (7 males, 3 females, 34.5 12.7 years, Y-BOCS: 27.8 4.6, HAMD-21: 13.3 1.9) and controls (7 males, 3 females, 34.4
12.8 years) was recorded, following an adaptation night. Sleep variables did not significantly differ in both groups except that stage
4 sleep was reduced in patients. Three of the patients with OCD, however, exhibited sleep onset REM periods (SOREMPs), i.e.
rapid-eye-movement (REM) latencies b10 min. Obsessive compulsive symptoms were significantly (P b 0.05) more severe in these
patients (Y-BOCS: 32 2.0) compared to those without SOREMPs (Y-BOCS 26 4.2). This is, to our knowledge, the first report of
sleep onset REM periods in OCD.
2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: Obsessive compulsive disorder; Sleep; Sleep onset REM period; SOREMP; REM latency; Polysomnography

1. Introduction port et al., 1981) in patients with OCD compared with

Sleep studies in patients with obsessive compulsive
disorder (OCD) are sparse and results inconsistent. Two
investigations in adults (Insel et al., 1982) or adolescents
(Rapoport et al., 1981) with OCD and matched healthy
controls found significant differences in polysomno-
graphic recordings in a variety of measures: In both
studies, patients with OCD had significantly less total
sleep time, less stage 2 sleep, and a shortened rapid-eye-
movement (REM) latency. Divergently, one study
showed significantly less (Insel et al., 1982), the other
significantly more stage 4 and slow-wave sleep (Rapo-
Corresponding author. Kraepelinstrasse 2-10, 80804 Munich,
Germany. Tel.: +49 89 30622 396; fax: +49 89 30622 548.
E-mail address: kluge@mpipsykl.mpg.de (M. Kluge).
0165-1781/$ - see front matter 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.psychres.2006.04.003
healthy controls. A third study, published only in
abstract form, reported a significantly impaired sleep
continuity and an increase of REM density in patients
with OCD (Voderholzer et al., 2001). In contrast, two
further studies did not observe major differences
between both groups, apart from a longer time awake
(Robinson et al., 1998) or a decreased sleep efficiency
(Hohagen et al., 1994) in patients with OCD. In only one
of these studies (Robinson et al., 1998) patients did not
concomitantly suffer from depression. In three others
(Rapoport et al., 1981; Insel et al., 1982; Hohagen et al.,
1994), 3250% of patients also fulfilled criteria of major
depression, considered to be secondary to OCD. In one
study, patients' characteristics were not reported in
detail (Voderholzer et al., 2001). The aim of this study
was therefore, to provide data on sleep in patients with
30 M. Kluge et al. / Psychiatry Research 152 (2007) 2935

OCD but without comorbid major depression, as an
episode of major depression can be associated with
characteristic alterations of sleep electroencephalogram
(EEG), such as a reduced REM latency (Kupfer, 1976;
Seifritz, 2001; Steiger et al., 1989). Other findings from
this study will be presented elsewhere.
2. Methods
2.1. Subjects
Ten inpatients (7 males, 3 females), aged 20 to 59
(34.5 12.7) years (weight: 75.2 13.2 kg, height:
176 10 cm;) meeting DSM-IV criteria of obsessive
compulsive disorder, and 10 matched healthy controls
(7 males, 3 females), aged 21 to 61 (34.4 12.8) years
(weight: 75.7 9.0 kg, height: 179 9 cm) were in-
cluded in this study. Controls without a lifetime or
family history of psychiatric disorders or sleep distur-
bances within the preceding 6 months were recruited
among the staff of the hospital and by advertisement.
Patients were required to have at least moderate obsessive
compulsive symptoms corresponding to a score of N 15 on
the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Obsessive compulsive symptoms, including checking
behaviors, washing and cleaning rituals, ordering and
counting compulsions, and obsessional thoughts were
moderate to extreme, Y-BOCS scores ranged from 22 to
34 (27.8 4.6). Exclusion criteria comprised an addition-
al concomitant axis I disorder (e.g. major depression) or
an axis II disorder as defined in DSM-IV, any serious,
unstable physical illness, and a pathological electroen-
cephalogram (EEG) or electrocardiogram (ECG). In order
to exclude patients with more than moderate depressive
symptoms, patients with a Hamilton Depression Rating
Scale (HAMD) total score N 16 were excluded (21-item
version). All subjects had to be drug-free for at least 7 days
prior to study entry. Fluoxetine had to be discontinued at
least 6 weeks before study entry. Three patients had been
previously treated for a major depressive episode. Written
informed consent was obtained from all patients and
controls. Ethical review board approval was given by the
Bavarian Medical Association (Bayerische Landesrzte-
kammer). Patients' illness variables at baseline are
displayed in detail in Table 1.
2.2. Study design
Study eligibility of all subjects was assessed by taking
the past and current psychiatric and medical history and
performing a physical examination and screening tests
(EEG; ECG; routine laboratory parameters; drug
screening; HAMD-21 and Y-BOCS, which were
assessed only in patients). The study comprised two
consecutive nights. The first night was intended for
adaptation of patients and controls to the sleep laboratory
setting. In the second night, polysomnographic record-
ings started at 2300 h and lasted until 0700 h when

Table 1
Illness variables of 10 patients with obsessive compulsive disorder at baseline
Patient, Age HAMD Y-BOCS Subjective sleep Duration of illness Medication prior to drug-free Duration of drug-free
sex (years) score score disturbances (years) interval (mg/day) interval
A.A., 59 9 32 None 17 Clomipramine (?) Several years
female
A.B., 20 15 34 None 1.3 Clomipramine (75) 9 days
male Chlorprothixene (75)
A.C., 23 14 23 Prolonged sleep 9 Levomepromazin (25) 18 days
female onset
A.D., 31 13 23 None 6 Benzodiazepine (510) 10 days
male
A.E., 43 12 32 None 0.8 Perazine (100) 7 months
male
A.F., 22 16 30 None 2.3 Paroxetine (60) 9 months
male
A.G., 29 13 29 None 10 Fluvoxamine (100) 2 years
male
A.H., 43 14 30 Nightly awakenings 2 Fluvoxamine (100) 10 days
male
A.I., 46 14 22 None 30 Venlafaxine (75) 13 days
female
A.J., 29 13 23 None 1.5 Benzodiazepine (520) 21 days
male Carbamazepine (200800) 14 days
 M. Kluge et al. / Psychiatry Research 152 (2007) 2935 31

patients were awakened, if necessary. In addition, 4 ml
blood was drawn every 20 min for determination of
cortisol, growth hormone, and ACTH (data will be
reported elsewhere). At 1900 h, an indwelling catheter
was placed in order to minimize effects on sleep by
venipuncture stress. For reducing nightly disturbances,
blood was drawn from the adjacent room by means of a
tubic extension. Sleeping was allowed from 2300 h on,
when light was switched off. The 2 days before and the
2 days of the study, coffee intake was restricted to one
cup per day, and other substances influencing vigilance
such as alcohol, or activities such as naps during the day
or excessive sports, prohibited.
2.3. Sleep-EEG analysis
Polysomnography consisted of two EEGs (C3-A2,
C4-A1, time constant 0.3 s, low pass filtering 70 Hz),
vertical and horizontal electrooculograms, an electromyo-
gram, and an ECG (Polysomnograph ED 24, Schwarzer
GmbH, Munich, Germany). Sleep stages were visually
scored per 30 s epoch according to conventional criteria
(Rechtschaffen and Kales, 1968) by experienced raters,
who were blind to patient group status. The following
sleep variables were calculated: sleep period time (SPT,
time from first epoch containing stage 2 sleep until final
awakening), total sleep time, time awake, sleep onset
latency (time between lights off and first occurrence of
stage 2 sleep), REM latency (interval between sleep onset
and first epoch containing REM sleep), slow wave sleep
(SWS) latency (interval between sleep onset and first
epoch containing stage 3 sleep), number of awakenings,
sleep efficiency (TST/SPT 100), and absolute time spent
in each sleep stage.
2.4. Statistical methods
Sleep and demographic variables were expressed as
mean standard deviation (S.D.). Differences between
patients and controls were tested for significance by
means of a multivariate analysis of variance (MANOVA)
with a significance level of = 0.05. In order to detect if
patients exhibiting and not exhibiting sleep onset REM
periods (SOREMPs) belong to the same population, the
KolmogorovSmirnov test was utilized. For comparison
of illness variables of patients with and without
SOREMPs, the t-test ( = 0.05) was used. Because of
the small sample size, the t-test had only exploratory
character. In particular, negative results (no rejection of
the null-hypothesis) have to be interpreted with great
caution because of high risk of type II error. In contrast,
positive results (rejection of the null-hypothesis) suggest
large group differences.
3. Results
Patients with OCD had significantly less stage 4 sleep
than healthy controls (P b 0.05). Other sleep variables did
not differ significantly (Table 2). Three of ten patients
exhibited a sleep onset REM period (SOREMP), as

Table 2
Comparison between sleep variables in 10 patients with obsessive compulsive disorder (OCD) and 10 matched healthy controls; sleep variables of
patients have been additionally shown divided into those with and without sleep onset REM periods (SOREMPs)
Patients Patients with SOREMPs Patients without SOREMPs Controls (n = 10) MANOVA
(n = 10) (n = 3) (n = 7) (F; P)
Sleep period time 453.6 18.7 438.5 17.4 459. 19.6 468.4 24.7 0.02; 0.90
(min)
Time awake 55.5 28.3 71.5 30.1 48.6 26.6 58.3 47.4 0.02; 0.88
Sleep onset latency 28.3 17.9 38.0 22.7 24.1 11.5 36.3 23.4 0.77; 0.39
(min)
REM latency (min) 55.5 41.1 4.0 1.6 77.5 23.3 71.5 17.1 2.45; 0.14
SWS latency (min) 30.4 25.8 55.3 29.1 19.7 9.5 17.3 12.2 2.14; 0.16
Number of 25.0 12.1 35.3 12.5 20.1 6.6 23.0 11.8 0.13; 0.73
awakenings
Sleep efficiency (%) 88 6 84 5 89 6 88 9 0.00; 1.0
Stage 1 (min) 30.6 10.4 31.2 12.3 30.3 10.6 30.7 9.8 0.00; 0.97
Stage 2 (min) 216.5 32.2 190.9 33.0 227.4 27.1 236.6 31.8 2.01; 0.17
Stage 3 (min) 36.7 15.7 34.5 29.3 37.7 9.1 28.7 14.5 1.49; 0.24
Stage 4 (min) 7.6 11.2 7.0 7.37 7.9 12.9 24.8 22.1 4.82; 0.04
SWS (min) 44.4 21.1 41.4 36.5 45.7 14.8 53.6 26.9 0.72; 0.41
REM (min) 101.1 24.3 99.7 25.0 101.7 25.9 85.4 23.0 2.25; 0.15
SWS: slow wave sleep; REM: rapid eye movement.
Significant difference between group of patients and controls (P b 0.05).
32 M. Kluge et al. / Psychiatry Research 152 (2007) 2935

4
Patients with obsessive compulsive disorder
Healthy subjects

Number

0
0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 > 90
REM latency [min]

Fig. 1. REM latencies in 10 patients with obsessive compulsive disorder and 10 healthy subjects.

defined as a REM latency b10 min (2, 4, and 6 min),
causing a numerically shorter mean REM latency in pa-
tients (Table 2). REM latencies of patients but not controls
were bimodally distributed (Fig. 1). Mean REM latencies
of patients with and without SOREMPs significantly
differed (P b 0.05). In addition, proportion of REM sleep
within the first night third was significantly (P b 0.05)
higher in patients with SOREMPs (36.4 4.7%) than in
those without SOREMPs (17.5 8.7%). Two of the
patients with SOREMPs had longer SWS latencies (93,
51, [22] min) compared to patients without SOREMPs
(936 min) and controls (946 min), contributing to the
numerically longer mean SWS latency in patients
(Table 2). Patients with SOREMPs had been drug-free
for 9 days (clomipramine 75 mg/day, chlorprothixene
75 mg), 10 days (fluvoxamine 100 mg/day) and several
years, respectively. Obsessive compulsive symptoms
were significantly (P b 0.05) more severe in patients
with SOREMPs (Y-BOCS score 32 2.0) than in those
without SOREMPs (Y-BOCS score 26 4.2). Other
characteristics such as depressive symptoms (HAMD-21:
SOREMPs: 12.7 3.2, without SOREMPs 13.6 1.3), and
age (SOREMPs: 40.7 19.6 years; without SOREMPs
31.9 9.3 years) did not differ significantly.
4. Discussion
30% of patients with OCD, but none of the healthy
controls, exhibited sleep onset REM periods (SOR-
EMPs). Otherwise, sleep patterns were comparable.
Merely stage 4 sleep was shorter in patients than in
controls. Two out of four full-papers published on sleep in
OCD as yet showed overall similar sleep pattern in
patients and healthy subjects (Hohagen et al., 1994;
Robinson et al., 1998), two showed various differences
(Rapoport et al., 1981; Insel et al., 1982). In the two latter
studies, sleep patterns in OCD resembled those in
depression. Among other sleep variables, less total sleep
time and a shortened REM latency, a core feature of sleep
in depression (Kupfer and Ehlers, 1989; Armitage and
Hoffmann, 2001) were found. Indeed, 44% and 50% of
patients with OCD in these studies simultaneously met
DSM criteria of a major depression. However, 32% of
patients in one of the studies not showing major
differences between both groups also suffered from
major depression (Hohagen et al., 1994), suggesting that
the different sleep patterns observed cannot be explained
by presence or absence of depressive symptoms. This
assumption is corroborated by the finding that REM
latencies did not differ between depressed and non- (or
less) depressed patients with OCD (Insel et al., 1982;
Hohagen et al., 1994). Reasons for the diverging findings
could comprise different patient characteristics (e.g. age,
severity of illness, frequency of sleep disturbances) or
methodological discrepancies (e.g. different sleep labo-
ratory settings or statistics).
In our study, the mean REM latency was numerically
shorter in patients with OCD than in controls. However,
this was exclusively caused by the three patients
exhibiting SOREMPs and not by a generally shorter
 M. Kluge et al. / Psychiatry Research 152 (2007) 2935
REM latency (Table 2). REM latencies in patients showed
a striking clear-cut bimodal distribution (Fig. 1). Patients
with a SOREMP appeared to be more severely ill than
those without a SOREMP.
This is, to our knowledge, the first report of SOREMPs
in obsessive compulsive disorder. SOREMPs, which may
occasionally occur in healthy subjects (Schulz and Lund,
1983) have also been reported in major depression,
psychotic depression (Kupfer and Foster, 1973), schi-
zoaffective disorder (Zarcone et al., 1987), and schizo-
phrenia. In depression, SOREMPs (REM latency
b 10 min) were found in up to 42% of patients (Schulz
et al., 1979; Ansseau et al., 1984). The likelihood of
SOREMPs appeared to increase with higher age (Ansseau
et al., 1984; Kumar et al., 1987; Pollmcher et al., 1997).
Both a unimodal distribution of REM latencies (Ansseau
et al., 1984; Pollmcher et al., 1997) and a bimodal
distribution with peaks between 020 and 5070 min
(Schulz et al., 1979; Coble et al., 1981; Kumar et al.,
1987) were reported. Occurrence of a SOREMP was
rather related to a more severe course of illness (e.g.
number of hospitalizations) than to current severity of
illness (Kumar et al., 1987; Staner et al., 1998). In
schizophrenia, SOREMPs were reported in up to 17% of
patients (Taylor et al., 1991). REM latencies tended to
show a bimodal distribution with peaks between 010 and
4080 min (Zarcone et al., 1987; Kempenaers et al., 1988;
Taylor et al., 1991; Lauer et al., 1997). Schizophrenic
patients with SOREMPs had more negative symptoms
than those without (Taylor et al., 1991). Consistently, the
REM latency had been shown to be inversely correlated
with not only negative symptoms (Tandon et al., 1992)
but also positive symptoms (Lauer et al., 1997; Thaker et
al., 1990). In line with the finding that SOREMPs (or a
short REM latency) are associated with a more severe
clinical course in depression and with more severe current
symptoms in schizophrenia, it has been hypothesised that
a short REM latency might be associated with some
more global clinical feature, such as severe and prolonged
psychiatric pain or turmoil; this, too, would cut across
diagnostic categories (Zarcone et al., 1987). Our findings
in patients with OCD are strongly supportive of this
assumption.
It is not fully clear to us why there are no other
reports on SOREMPs in patients with OCD. We deem it
rather unlikely that SOREMPs observed in our study
were provoked by confounding factors possibly reduc-
ing REM latency.
Firstly, previous intake of psychotropic medication.
Discontinuation of various tricyclic antidepressants and
serotonin reuptake inhibitors (SSRIs), which may de-
crease amount of REM sleep and increase REM latency
33
(Dunleavy et al., 1972; Steiger, 1988; Silvestri et al.,
2001; Feige et al., 2002), may reactively cause an
overcompensatory increase of REM sleep and decrease
of REM latency (REM rebound). This effect appears to
be most pronounced in the first days after drug
discontinuation. Already after a wash-out period of 5 to
7 days and 7 to 10 days, respectively, EEG sleep patterns
were repeatedly found to be similar in previously
treated and never treated patients with depression
(Berger et al., 1983; Lauer and Pollmcher, 1992). As
well in patients with OCD, a 1-week wash-out period
appeared to be sufficient to avoid rebound effects: In a
relatively large study on sleep in OCD, including 22
patients, sleep variables (including REM latency) in
patients and healthy controls were comparable after
only 1 week of wash-out, thus not suggesting a major
drug effect (Hohagen et al., 1994). In contrast, a smaller
study in healthy adults reported REM rebound phe-
nomena after discontinuation of tricyclic antidepres-
sants (two of them received clomipramine) for up to
3 weeks (Dunleavy et al., 1972). In accordance with
this, a single case study in a healthy volunteer receiving
clomipramine found after 1 week of drug discontinu-
ation still REM rebound, e.g. a moderately (to 57 min)
decreased REM latency (Steiger, 1988). But neither in
this case nor in the previously mentioned study SO-
REMPs were reported. Therefore, it appears unlikely
that the SOREMP (REM latency: 4 min) in the one
patient who received clomipramine until day 9 before
study entry was a REM rebound phenomenon. The
same holds true for the patient who received fluvox-
amine until day 10 before study entry: A more recent
study showed a mean REM latency reduction to 86 min
in the 4 days following discontinuation when the
strongest REM rebound is expected (Silvestri et al.,
2001). This patient reported repeated nightly awaken-
ings. We do not regard the SOREMP as a rebound
phenomenon due to REM sleep deprivation, as the absolute
amount of REM sleep was not increased (95.5 min; mean:
99.7 25.0). Furthermore, the third patient with a SOR-
EMP had been drug-free for several years.
Secondly, REM latency moderately decreases with
age (Ohayon et al., 2004): Age did not relevantly differ
between patients with and without SOREMPs in this
study; in addition, age of patients in the other studies on
sleep and OCD were comparable (Insel et al., 1982,
Hohagen et al., 1994; Robinson et al., 1998), except in
the study conducted in adolescents (Rapoport et al.,
1981).
Thirdly, an accompanying depression may elicit
SOREMPs (Schulz et al., 1979; Ansseau et al., 1984;
Staner et al., 1998): Depressive symptoms were at most
34 M. Kluge et al. / Psychiatry Research 152 (2007) 2935
moderate in all patients and similar in patients with and
without SOREMPs. No patient fulfilled criteria of a
current major depression. Moreover, only one of the pa-
tients with a SOREMP had previously suffered from a
single depressive episode, 27 years before. Above all, a
correlation between REM latency and severity of depres-
sive symptoms in patients with OCD could not been de-
monstrated (Insel et al., 1982; Hohagen et al., 1994). In
our study, patients exhibiting SOREMPs had at least
severe obsessive compulsive symptoms. Accordingly, a
minor severity of illness could explain the lack of SO-
REMPs in the other studies. In fact, in the two studies
using the Y-BOCS, mean obsessive compulsive symp-
toms were lower (Hohagen et al., 1994; Robinson et al.,
1998). On the other hand, some patients were severely
affected as well in these samples. The other two studies
were not easily comparable because another scale was
used for quantification of obsessive compulsive symp-
toms (Rapoport et al., 1981; Insel et al., 1982).
Finally, it cannot be ruled out that SOREMPs did either
not occur or were simply not reported in the 4 studies
published on sleep in OCD so far. The latter seems most
probable to us, considering that various, partly large-scale
studies on sleep in depression, in which SOREMPs could
have been expected, did also not report SOREMPs (Kup-
fer et al., 1981; Steiger et al., 1989; Hubain et al., 1996).
Findings from animal studies suggest that REM sleep is
promoted by cholinergic cells in the brainstem and im-
peded by both serotonergic raphe neurons and noradre-
nergic locus coerulus neurons which are strongly inhibited
during REM sleep (Hobson et al., 1975; Kametani and
Kawamura, 1990; Marrosu et al., 1995; Datta and Siwek,
1997; Rodrigo-Angulo et al., 2005). A shortened REM
latency may therefore indicate a cholinergic hyperactivity
or an aminergic hypoactivity (Hohagen et al., 1994). There
is increasing evidence that central serotonergic neuro-
transmission is decreased in obsessive compulsive dis-
order (Barr et al., 1992; Hesse et al., 2005). Accordingly,
reduced REM latencies could be expected in patients with
OCD. In our study however, a general reduction of REM
latencies compared to healthy controls was not found. But
a subgroup of 3 patients, being particularly ill, exhibited
SOREMPs, possibly reflecting a disinhibition of REM
sleep. This presumption is supported by the finding that
the proportion of REM sleep in the first night third was
significantly increased in patients with SOREMPs (36.4
4.7%) compared to those without SOREMPs (17.5
8.4%), although the absolute amount of REM sleep
(related to the whole night) was not increased. SOREMPs
without increased amount of REM sleep have been also
reported in depression and schizophrenia (Ansseau et al.,
1984; Taylor et al., 1991), which possibly could point to a
mechanism linked to psychopathology. In contrast,
decreased REM latencies due to drug withdrawal
(Dunleavy et al., 1972; Steiger, 1988; Feige et al., 2002)
or non-pharmacological REM sleep deprivation (Endo
et al., 1998; Nielsen et al., 2005) were usually associated
with an increased amount of REM sleep.
A limitation of this study is that sleep EEG recordings
might have been affected by nocturnal blood drawings.
However, this influence was similar in both groups, thus it
did not explain: the occurrence of SOREMPs in patients.
A further limitation is that sleep EEGs were recorded
during one night only, possibly resulting in data slightly
different from those averaged over several nights. How-
ever, this night represented a normal night since patients
had a regular sleep schedule (bedtime 23:00; awakening
07:00) for at least 1 week prior to study entry. In addition,
a sleep laboratory bias was minimized by an adaptation
night preceding the night when polysomnographies were
performed.
In conclusion, our findings suggest that sleep onset
REM periods may occur in patients with obsessive com-
pulsive disorder. On an average, patients with SO-
REMPs appeared to be more severely ill than those with-
out SOREMPs. Overall, sleep patterns in patients with
OCD and healthy subjects were comparable.
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