Sleep-related violence and low serum cholesterol: A preliminary study

INTRODUCTION

Violent behavior during sleep (VBS) includes a broad range of behaviors: benign dream enactment (kicking, jumping out of bed, running), self-mutilation, sexual assault, attempted murder, murder and suicide. The VBS can be directed to other subjects, to objects, or to self.¹ In 1989, Schenck et al. published a clinical and polysomnographic study on 100 consecutive adult patients complaining of sleep-related injury.² They identified several disorders as being responsible for causing nocturnal violence: sleepwalking, sleep terrors, rapid eye movement (REM) sleep behavior disorder, nocturnal psychogenic dissociative disorders, nocturnal seizures, obstructive sleep apnea, and periodic limb movement disorder. More recently, Ohayon et al. reported that VBS during sleep affected 2% of the population.³ They identified a number of sleep, mental disorder, and other general health factors that characterize those experiencing episodes of VBS. Night terrors, daytime sleepiness, sleep talking, bruxism, and hypnic jerks were more frequent in subjects with violent or harmful behavior during sleep than the non-violent subjects, as were hypnagogic hallucinations, the incidence of smoking, caffeine and bedtime alcohol intake. Many neurologic and psychogenic causes of sleep-related violence were described in the literature.^4,5

The relationship between serum cholesterol and psychiatric disorders had been the focus of several studies in recent decades. An association between high cholesterol levels and anxiety disorders, in particular panic disorder, had been demonstrated in recent years.^6–9 In contrast, a low cholesterol level was found in patients with major depression or suicidal behavior.^10–17

Another interesting topic is the relationship between serum cholesterol and violent behavior. Human and animal research indicates that low or lowered cholesterol levels may reduce central serotonin activity, which in turn is causally linked to violent behaviors. Many trials supported a significant relation between low or lowered cholesterol levels and violence for 30 years.¹⁸ Moreover, low cholesterol is associated with increased subsequent criminal violence.¹⁹ In the present study, we examined whether there was a relationship between serum cholesterol level and sleep-related violence.

METHODS

The subjects of the study were 15 patients with VBS and 15 normal control subjects. All of the patients included in the study were selected from a group of patients at the Clinical Research Program for Sleep and Dissociation in Van City, Turkey. A clinical sleep–wake interview with the patient and his or her bed partner was performed. Medical and psychiatric history, alcohol and drug use history, past or current physical, sexual, and emotional abuse history were obtained. Psychiatric and neurological interview and examinations were performed. Extensive overnight polysomnographic monitoring, with continuous audiovisual recording, was performed at the hospital. International Classification of Sleep Disorders (ICSD)-revised criteria²⁰ was used for diagnosis. Characteristics of patients with VBS were shown in Table 1. To assist in the determination of the putative role of underlying sleep disorders in specific violent acts, we used clinical and polysomnographical guidelines proposed by Mahowald and Schenck.²¹

The patient and control groups were matched for sex, age, and weight. For each group, the subjects were 13 women and two men. The patients ranged in age from 17 to 61 years (mean 26.8 ± 19.6) and in weight from 57 to 78 kg (mean 63.7 ± 9.2). The control subjects ranged in age from 18 to 60 years (mean 27.2 ± 18.3) and in weight from 59 to 79 kg (mean 64.1 ± 8.7). There was no significant difference on age and weight between the groups (P > 0.05). No subject had alcohol or drug abuse, abnormal electrocardiograms, or unstable medical conditions. All subjects gave informed consent to participate in the study and were requested to avoid medications affecting lipid levels for at least 2 weeks. Venipuncture was done in a sitting position by using a tourniquet. A total of 5 mL blood was drawn after overnight fasting in both groups. Blood was then centrifuged at 940 g for 1 min in a refrigerated centrifuge and was separated from the serum samples from the cells. Cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol levels were determined in the serum by commercially available kits (Roche Diagnostic GmbH, Mannheim, Germany) on a Hitachi 747 autoanalyser (Hitachi Ltd, Tokyo, Japan). An enzymatic colorimetric method was used for cholesterol and triglyceride determination. High-density lipoprotein-cholesterol was measured using the direct HDL-cholesterol method. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald formula.²²

The Statistical Package for the Social Sciences (SPSS), release 10 was used for statistical analysis. Data analyses were performed by using Student's t-test (two-tailed).

RESULTS

The mean serum total cholesterol levels of VBS and control groups were 166.1 mg/dL (SD = 44.9) and 194.3 mg/dL (SD = 28.8), respectively. The Student's t-test revealed a significant difference between the groups (t = 2.05; P < 0.05). Mean triglyceride level was 107.8 mg/dL (SD = 70.3) and 162.4 mg/dL (SD = 68.9) and there was a significant difference between the groups (t = 2.15; P < 0.05). The patients with VBS had also lower serum LDL levels (mean 89.1 ± 31.7) than the control subjects (121.4 ± 25.2) (t = 2.84; P < 0.01). High-density lipoprotein levels did not differ for patients (46.4 ± 13.8) and the controls (40.5 ± 9.9) (t = 1.25; P > 0.05).

DISCUSSION

In the present study, we found that patients with VBS had lower serum total cholesterol, triglyceride, and LDL levels than the healthy subjects. The present study is the first, to our knowledge, that examines the association between sleep-related violent behavior and serum cholesterol. Low serum cholesterol level in daytime violent or homicidal behavior has been previously noted by some studies,^18,19 while low serum cholesterol level in violence during sleep has not been reported in the literature.

The effect of low or lowered cholesterol on serotonergic neuronal activity has been seen by many as a plausible explanation of the association between violence and low cholesterol. Indeed, the association between diminished brain serotonin transmission and aggressive behavior has been established by recent studies.²³ In biological membranes, cholesterol is distributed in the phospholipid layer, where it is loosely bound and so can freely exchange with serum cholesterol. In the present study, we found that the LDL level was lower in VBS group than in the control group. The highest proportion of cholesterol is found in the LDL that is important to transport cholesterol to extrahepatic tissues. Thus, especially, decreased LDL-cholesterol level may change the fluidity of membranes. A reduction in serum lipids may decrease brain-cell-membrane cholesterol, lower the lipid microviscosity, and decrease the exposure of protein serotonin receptors on the membrane surface, resulting in a poorer uptake of serotonin from the blood and less serotonin entry into brain cells.¹⁰ There is also evidence that the active transport of serotonin via the serotonin uptake pump is sensitive to changes (decrease) in membrane fluidity and that the addi-tion of cholesterol decreases serotonin transport.²⁴ Recently, Terao et al. revised the hypothesis in the viewpoint of their hypothesis that low cholesterol may decrease post-serotonergic receptor function.²⁵

Recent research indicates that dorsal raphe neuronal activity and serotonin release may be actively modulated during sleep and waking. It was reported that dorsal raphe nucleus neurones were most active during waking, the activity was considerably lower during slow wave sleep and was lowest during REM sleep.²⁶ An association between low serum lipid levels and VBS shown in the present study may related to effects of low cholesterol on serotonergic neuronal activity. It was suggested that violent behavior may be associated with impaired presynaptic release of serotonin and compensatory increased in 5-HT2 receptors.^23,27 However, 5-HT2 agonists have been shown to dose-dependently increase waking and reduce slow waves sleep (SWS) and REM sleep, while 5-HT2 antagonists increase SWS but not REM sleep.²⁶ Selective serotonin reuptake inhibitors stimulate 5-HT2 receptors and result in insomnia.²⁸ They are also one of the causes of REM sleep behavior disorder and nightmares.⁵ Thus, theoretically, it may be suggested that low cholesterol in the central nervous system effects serotonergic neuronal activity and some types of 5-HT receptors, then causes violent behavior during sleep. However, this does not seem to fully answer how serum lipid levels are related to sleep-related violence. In a previous study,²⁹ we demonstrated that sleep panic attacks, one cause of sleep-related violence, was related to high serum levels. We found that patients with recurrent sleep panic had higher cholesterol levels than other panickers, although the patients represented a subgroup of panic disorder. However, the underlying neurobiological mechanism concerning the difference that the violence occurs in daytime or during sleep is not completely clear. It is possible to speculate that the interactions in central serotonergic activity and cholesterol in the brain are relatively different in violent behaviors during REM sleep, non-REM sleep, and awake state. If the findings in the present study are confirmed with future studies, it will be plausible to discuss the association of cholesterol with VBS such as daytime violence.