FIRST NIGHT EFFECT IN DIFFERENT FORMS OF SCHIZOPHRENIA
VADIM S. ROTENBERG
J. HADJEZ, T. MARTIN, P. INDURSKY,
N. MICHAILOV, Y. BARAK, R. WEISS, Y. GUTMAN, E. SHAMIR
Abarabanel Mental Health Center Tel Aviv, Israel,
Dynamische Psychiatrie/Dynamic Psychiatry, 1998, v. 172/173, Heft
Polysomnograhpy was performed during two consecutive nights in 20
schizophrenic patients and in 10 healthy controls. First night
effect (the increase of REM sleep latency on the first night by at
least 30 minutes in comparison to the second night) was present in
35% of schizophrenic patients and in 80% of healthy subjects. The
increase of REM sleep latency in schizophrenic patients was
accompanied by the decreased sleep efficiency in the same night as
well as by the increased number of awakenings in comparison to
healthy subjects. The mean age of subjects and the mean data of
positive symptoms were higher in schizophrenic patients with the
first night effect than in patients without first night effect.
Search activity concept is used for the explanation of these data.
First night effect is the alteration of the sleep structure in
the unfamiliar environment of a sleep laboratory. On the first
night of sleep investigation, in comparison to the subsequent
nights, sleep structure of healthy subjects is characterized by the
increased REM sleep latency combined with a moderate REM sleep
reduction, especially in the first part of the night (Agnew
et al. 1966). Sleep latency is also often increased, as well as the
number of sleep stages shifts, while sleep efficiency is decreased.
Other changes in sleep structure, like decreased slow wave sleep
(Agnew et al. 1966) are less obligatory for the definition
of the first night effect (Schmidt, Kaelbling 1971).
First night effect reflects the increased level of vigilance as a
normal reaction of the brain to a new situation. Thus the
abovementioned physiological manifestation can be used as a
measurement of the subject's adaptability to a new environment.
Depressed patients often do not show evidence of the first night
effect (Ansseau et al. 1985; Akiskal et al. 1982).
This absence of the first night effect may be related to the
decreased adaptability of depressed patients. According to our data
(Rotenberg et al. 1997a,b) depressed patients without first
night effect display more mood-congruent psychotic features in
their clinical picture, are resistant to antidepressive medicine
and require for the positive treatment outcome. However, it is
not known whether the absence of the first night effect
characterizes only psychotic depression, or it is absent also in
other psychotic disorders.
In order to answer this question, we decided to investigate
schizophrenic patients. According to our knowledge, a systematic
investigation focused on the first night effect in schizophrenic
patients was previously not performed. Neylan et al. (1992)
have not found first night effect in schizophrenic patients on
and off haloperidol therapy; however, they have analyzed only the
mean data for a combined group of patients, without any attempt to
divide the group into subgroups according to the relative duration
of the REM sleep latency. It seems worthwhile to compare such
subgroups in order to discover factors (clinical or psychological)
That can be responsible for the presence or absence of the first
night effect in schizophrenic patients. It is also reasonable to
compare schizophrenic patients with depressed patients with and
without first night effect.
SUBJECTS AND METHOD
We investigated 20 patients with chronic schizophrenia, 13 men and
7 women with mean age - 45,8 6,3 years old. Patients have been
informed about the investigation and we have received their consent
to participate in the investigation. Clinical evaluation of the
disease was performed by using the structuralized clinical
interview, and the diagnosis was established according to the
DSM-IV criteria. 11 patients suffered from paranoid schizophrenia,
5 from residual type of schizophrenia, 3 patients from disorganized
schizophrenia and 1 patient from schizo-affective disorder.
Duration of disease ranged from 11 to 39 years ( mean duration was
21,6 4,7 years). PANSS ratings were obtained in order to evaluate
the severity of positive and negative signs (Kay et al.
1987). Patients were free from somatic medical problems. All
patients were on neuroleptic medication during the investigation
and their treatment was unchanged during 60 days prior to the
polysomnography. Hypnotic medication was stopped at least two weeks
prior to the polysomnography.
The control group consisted of 10 healthy subjects, 4 women and 6
men, with the mean age 40,38,1 years without any sleep complaints
and without medical problems. They had no mentally ill patients in
Sleep data were collected from all subjects on two consecutive
nights, including the first night. Lights were usually turned off
between 10:00 and 10:30 p.m. and turned on between 6:00 and 6:30
a.m. Electroencephalogram, submental electromyogram and
electrooculograms were recorded on an electroencephalograph
Neurofax EEG - 4400. EEG and EOG were recorded at a low filter
setting of 0.3 Hz.
Polysomnograms of 60 nights were analyzed according to
international criteria (Recbtschaffen, Kales 1968). Sleep
onset was defined as the first minute of stage I following by at
least 10 minutes of stage I sleep, interrupted by no more than 2
minutes of awakening. REM sleep latency corresponded to the time
between sleep onset and the first REM period including intervening
After the end of the investigation, all patients were divided into
two groups according to the presence or absence of the first night
According to our arbitrary criteria (Rotenberg et al. 1997),
first night effect was present if REM sleep latency on the first
night of study was at least 30 minutes longer than REM sleep
latency on the second night.
One-way analysis of variance (ANOVA) and Kruskal-Wallis Test were
used for sleep variables in 3 groups x 2 nights. If the ANOVA and
Kruskal-Wallis Test were found to be significant at the p< 0.05
level, they were followed by the paired Student T-test in order to
compare sleep variables of control group and both groups of
patients. We have used also the Pearson Correlation Coefficient in
order to find relationships between REM sleep latency, age and
positive and negative symptoms. ANCOVA was used in order to
differentiate the role of age from the role of positive symptoms in
the increase of REM sleep latency on the first night ( we have used
positive symptoms as independent variables by making them nominal -
more or less than averaged 17 points), age was used as a
confounding factor, and the difference between REM sleep latency in
the first and second nights - as a dependent variable).
First night effect according to our criteria was present in 8
subjects of our control group (80%) and in 7 schizophrenic patients
(35%, Group I). In 13 patients first night effect was not
demonstrated (Group II). Group I contained 2 women and 5 men; Group
II contained 5 women and 8 men. The mean age for Group I was 54,0
13,3 years, and for Group II 35,5 6,6 years (p<0.02). The
mean duration of the disease in Group I was 26,2 6,3 years and in
Group II 18,3 3,8 years (p<0.05). Paranoid schizophrenia was
present in 5 patients of Group I and in 6 patients of Group II.
Residual schizophrenia was present in 2 patients of Group I and in
3 patients of Group II (difference between groups is statistically
nonsignificant). Treatment was similar in both groups although
fluphenazine was used non-significantly more often in Group II. The
selected groups were different according to the representation of
positive symptoms. In Group I the mean datum of positive symptoms
was 22,16 6,39, while in Group II it was 14,1 5,2 ( p<
0.02). The mean data for hallucinations in Group I was 2,8 and for
delusions 3,8, while in Group II 1,4 and 2,2, respectively. At the
same time, negative symptoms were almost equal in both groups (27,8
6,3 in Group I and 28,0 3,4 in Group II).
When the ratio of positive to negative symptoms was higher than
0.6, first night effect was present in 71% of all cases, while when
this ratio was lower than 0.4 first night effect was present in
only 17% (p< 0.05). In patients without first night effect
this ratio was higher than 0.6 in 20% of all cases, while in
patients with first night effect in 83% (p<0.02). The Pearson
Correlation Coefficient between age and positive symptoms was 0.638
for the united group of patients (p<0.01) and 0.785 for Group I
(p<0.06). ANCOVA does not discriminate the influence of age and
positive symptoms on the difference between REM sleep latency on
the first and the second night.
ANOVA and Kruskal-Wallis Test were significant for the following
- Sleep efficiency: ANOVA Fv = 9.239, PROB F- 0.0001;
Kruskal-Wallis Test (KWT): Chisq. + 21.257, DF=5, PROB Chisq. -
- Awakenings: ANOVA Fv = 3.197, PROB F - 0.0141; KWT: Chisq.
9.8558, PROB Chisq. - 0.0794.
- REM latency: ANOVA Fv. = 6.486, PROB F - 0.0001; KWT: Chisq.=
17.493, PROB Chisq. - 0.0037.
- REM1: ANOVA Fv + 4.611, PROB F - 0.0014; KWT: Chisq.= 18.790,
PROB Chisq. - 0.0021.
- REM1%: ANOVA Fv = 3.699, PROB F - 0.006; KWT: Chisq. = 21.661,
PROB Chisq. - 0.0006.
In Group I sleep efficiency on the first night was significantly
(p<0.01) lower than on the first night of normal control, on the
first night of Group II (p<0.02) and on the second night of
Group I (p<0.02). The number of awakenings on the first night of
Group I was increased in comparison to the first night of normal
control (p<0.02). On the second night the first episode of REM
sleep was increased in comparison to REM 1 of the second night in
the control group (p<0.05).
In Group II on the first night REM 1 was increased in comparison to
REM 1 of the first night in the control group (p< 0.05). On the
second night of the same group this variable was also increased in
comparison to the second night of the control group (p<0.001).
Thus, only REM 1 on the first night of Group I was not increased in
comparison to the control group. The ratio of the 1st REM period to
the total amount of REM sleep on the first night was not increased
in schizophrenic patients. In Group I on the first night this
variable was significantly less than on the second night
First night effect was present in only 35% of our schizophrenic
patients, less often than in the healthy control group (80%) and
less often than reported among depressed patients. According to our
data (Rotenberg et al. 1997a), as well as to Ansseau
et al. (1985), first night effect is present in almost 50% of
depressed patients. If only a minority of schizophrenic patients
display first night effect, it is not surprising that some others
(Neylan et al. 1992; Julien et al. 1980) were unable
to find this effect in schizophrenic patients. Ganguli et
al. (1987) have found a substantial difference between REM sleep
latency on the first and second night (first night effect) almost
in a half of young non-treated schizophrenic patients.
Sleep structure in schizophrenic patients with the first night
effect is in general similar to the sleep structure of healthy
controls. The main difference between Group I and the control group
is on the first night: In schizophrenic patients sleep efficiency
is decreased and the number of awakenings is increased. Thus it is
possible to suggest an exaggerated first night effect in Group I
in comparison to the control group.
What determines the presence or absence of the first night effect
in schizophrenia? It is the most interesting and the most difficult
question. All our patients were treated by neuroleptics at the time
of sleep investigation. Thus it is necessary to exclude the
possibility that neuroleptics caused absence of the first night
effect in most patients. However, both groups of patients have
been treated by neuroleptics, and Group I received this treatment
even for a longer period. Secondly, Neylon et al. (1992)
have not found first night effect in schizophrenic patients on
and off neuroleptic treatment, while Ganguli et al. (1987)
founnd that first night effect was absent in most of their
Patients of Group I in the present investigation were significantly
older than patients of Group II, and are characterized by the
higher positive symptoms score. Unfortunately, it was impossible to
discriminate the role of age and the role of positive symptoms in
the first night effect: It was a positive correlation between
both variables. Of course, it is a shortage of this investigation.
There were only two patients younger than 40 years with high
positive symptoms, and these patients demonstrated the absence of
the first night effect. On the other hand, one patient was 47 years
old, with low positive symptoms, and in this case first night
effect was also absent. At the same time, members of our control
group who demonstrated first night effect are younger than
patients of Group 1. In depressed patients those who display first
night effect are of the same age as patients without first night
effect (Rotenberg et al. 1997a). In the investigation of
Ganguali et al. (1987) almost a half of patients
demonstrated first night effect, although all patients were young..
Published data according the role of age in the first night
effect are contradictory, however in normal young subjects first
night effect in the laboratory is a typical finding
(Tousaint et al. 1995; Woodward et al. 1996). In aged
healthy subjects, in some investigations first night effect was
present (Aber et al. 1989; Wauquier et al. 1991) and
in other it was absent ( van Hilten et al. 1989). Thus, it is very
unlikely that first night effect is directly determined by the
age, but it is very possible that in schizophrenic patients age
contributes to the positive symptoms in determining the first
Positive symptoms may play a definite role in the first night
effect. There are some reasons for such suggestion:
1. Patients with positive symptoms are usually hypersensitive to
events they estimate as significant and related to them. It was
shown (Kim et al. 1993) that schizophrenic patients with
positive symptoms display an exaggerated orienting reaction, and
first night effect is a particular orienting reaction. At the
same time, schizophrenic patients with the domination of negative
symptoms demonstrate a failure to respond (Frith 1992).
2. Schizophrenic patients with positive symptoms display higher
reactivity to sensory and affective stimuli in comparison to
schizophrenic patients with negative symptoms (Docherty
1996). Such sensitivity may increase with age.
3. A relative higher response of the brain monoamine system in
patients with positive symptoms, in comparison to patients with
negative symptoms Wolkin et al. 1996), may also explain the
appearance of the first night effect as an exaggerated reaction
in a new environment.
4. Neylan et al. (1992) have shown that the relative
increase of psychotic symptoms after neuroleptic withdrawal
correlates negatively with REM%. It means that REM sleep pressure
is decreased. As a result REM sleep latency can be increased on the
first night of investigation (in opposite to those depressed
patients who have a high REM sleep pressure and a low REM sleep
flexibility, Rotenberg et al. 1997a).
The decreased REM sleep requirement in positive schizophrenia was
predicted theoretically by the Search Activity concept
(Rotenberg 1994). Search activity is defined as active
goal-oriented behavior in an uncertain situation, i.e. in the
absence of a definite forecast of the results of such activity but
with constant monitoring of the results at all stages of activity.
Stereotyped behavior, panic, depression and learned helplessness
are opposite to search activity (Rotenberg 1984;
Rotenberg, Boucsein 1993). It was shown (Rotenberg 1984)
that all forms of behavior that include search activity increase
body resistance to various forms of artificial and natural
pathology. It was also shown (Rotenberg 1993) that search
activity decreases and renunciation of search increases REM sleep
requirement, and it was proposed, that REM sleep provides the
restoration of search activity. According to many features (active
and an unpredictable character of events in delusions and
hallucinations; increased activity of the brain monoamine system)
it is possible to consider positive symptoms as a peculiar false
oriented search activity. It can decrease the REM sleep requirement
and exaggerate the first night effect.
It is interesting to discuss the difference between schizophrenic
patients with positive symptoms and patients with psychotic
depression. The latter demonstrate an absence of the first night
effect (Rotenberg et al. 1997a). Also according to
Ganguli et al.(1987), patients with delusional depression
usually do not demonstrate the decrease of REM sleep latency on the
second night. It is possible to speculate that the difference
between schizophrenia and psychotic depression is caused by the
difference in psychotic features in these two groups and by the
difference in the general clinical context in which psychotic
features appear in schizophrenia and depression. While
schizophrenics display hallucinations and delusions causing an
active and outside oriented, although inappropriate, search
behavior, delusions in depressed patients are often mood-congruent
and are related to the feeling of guilt, worthlessness and failure,
to ruminative self-blaming and self-anihilation. Such delusions
provide a basis for the passive behavior (renunciation of search,
Rotenberg 1994b). It was shown (Parker et al. 1995)
that psychotic depressive patients, in comparison to melancholic
patients and to major depression without psychotic features were
significantly more likely to demonstrate marked psychomotor
disturbances, to report feeling sinful and guilty, to suffer from
constipation, terminal insomnia, appetite loss and loss of interest
and pleasure. It was also shown (Coryell et al. 1996) that
psychotic features denote a lifetime depression of greater
Our approach to the difference between psychotic mood-congruent
depression and schizophrenia is in the line with data
(Ayuzo-Guttierez et al. 1985) that the cortisol non-suppression
on the dexamethason suppression test is most prominent in
depression with mood-congruent delusions, in comparison to both
non-psychotic depression and depression with mood-incongruent
delusions. Lower rates of non-suppression were also observed in
schizophrenia (Schatzberg et al. 1985). It means that
psychotic feature in depression and schizophrenia may have
different connotations, and this proposition is confirmed by our
data derived from sleep investigation. In psychotic depression the
active reaction to the unfamiliar sleeping environment is
diminished, and REM sleep requirement is increased, as a result
first night effect is abolished. In schizophrenia with positive
symptoms, the orienting reaction to the new environment is
increased, while REM sleep requirement is decreased, and first
night effect is prominent. However, this speculation must be
verified in further investigations. It would be also necessary in
future to investigate first-episode schizophrenic patients with
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