Low cholesterol and aggression in bipolar disorders

Abstract

Sir: In the hypotheses which was published recently [1], the author hypothesized that epidermal stem cells (ESCs) played a substantial contributory role in the pathogenesis of hypertrophic scars. We had already noticed the function of scar keratinocytes in the pathogenesis of hypertrophic scars, and had proved that scar keratinocytes secrete more cytokines and growth factors [2,3]. In our way to explore the mechanism of keratinocytes participating in the pathogenesis of hypertrophic scars, we have received a new idea that keeping normal composition of epidermis cells type is of great importance, because ESCs and transit amplifying cells in scar epidermis were much less in number than that in normal skin [4]. Our research also revealed a significant epidermal thickening in the hypertrophic scars with excessive cell layers above the basal layer. The basal cell markers b1 integrin, K19 and K14 decreased their expression in hypertrophic scars relative to normal epidermis by immunohistochemistry. The more meaningful finding was that Notch1 and Jagged1 were significantly increased their expression in hypertrophic scar than in normal epidermis [5]. It is well known that Notch may play a key role in linking the control of epidermal proliferation and differentiation [6]. Aberrant Notch signaling reIt is well known that most patients with bipolar disorders are not aggressive during their episodes of illness or in remission, but practitioners should expect that about one in four of bipolar patients will develop aggressive behaviour at some points. We suggest that an easily detectable biological marker of aggression in these patients might be a low level of serum cholesterol. Mounting evidence suggests a relation between low cholesterol and violence, aggression, and hostility [1]. Low levels of blood cholesterol have been shown to be associated with increased impulsivity among young men [2]. In particular, it has been found that bipolar disorder male patients with a history of suicide attempts have lower levels of serum cholesterol compared to those patients without suicide attempts [3]; in a recent study [4] in which cholesterol content was measured in cortical and subcortical tissue of brains from 41 male suicide completers and 21 male controls, violent suicides were found to have lower gray matter cholesterol content overall compared with nonviolent suicides and controls. Furthermore, familial hypobetalipoproteinemia, a rare genetic disorder of lipoprotein metabolism resulting in lifelong very low levels of LDL-cholesterol, has been shown to be associated with an increased risk of violent behaviour in some families [5]. Low cholesterol and violent behaviour might be related to decreased serotonin transmission and reduced lipid microviscosity of neuronal cell membranes, resulting in decreased serotonin receptor function and inhibited serotonin transmission, which may lead to a poorer suppression of impulsive behaviour. Indeed, it has been suggested that low blood cholesterol levels and resulting low brain serotonin levels prompted our prehistoric ancestors to aggressively hunt food for survival [6]. Aggression in bipolar disorders is a complex behaviour which can be influenced by comorbidity with substance use, personality disorders, and also biological markers. Low cholesterol levels might represent an important marker in order to recognise bipolar patients with biological predisposition to aggressive behaviour.