FIRST NIGHT EFFECT IN DIFFERENT FORMS OF SCHIZOPHRENIA
(PILOT INVESTIGATION)

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Publication Date:
February 28, 2013

VADIM S. ROTENBERG vadir@post.tau.ac.il 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 5/6, 421-430.

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.

INTRODUCTION

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 their families.

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 awake time.

After the end of the investigation, all patients were divided into two groups according to the presence or absence of the first night effect.

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.

STATISTICS

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).

RESULTS

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.

SLEEP VARIABLES

ANOVA and Kruskal-Wallis Test were significant for the following variables:

- Sleep efficiency: ANOVA Fv = 9.239, PROB F- 0.0001; Kruskal-Wallis Test (KWT): Chisq. + 21.257, DF=5, PROB Chisq. - 0.0007.

- 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 (p<0.05).

DISCUSSION

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 unmedicated patients.

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 night effect.

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 severity.

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 acute positive symptoms.

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