By Robyn Holden
THE CAUSE OF GENERALIZED ANXIETY STATES.
INTRODUCTION The cause of various mental illnesses has been extensively studied by Holden, R.J.1 in relation to brain insulin abnormalities and regional cerebral blood flow (rCBF). It has been found from wide ranging theoretical research that inflammatory cytokines, a molecule secreted by immune cells, promotes inflammatory reactions. THE INFLAMMATORY CYTOKINES AND GLUCOSE TRANSPORTERS. There are six inflammatory cytokines: interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-1 beta (IL-1B), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma). However, the three cytokines most important for the purposes of this discussion are: IL-1, TNF-alpha and IFN-gamma. It has been observed that when the inflammatory cytokines are mildly elevated, insulin secretion is increased in the brain, and when the inflammatory cytokines are moderately or highly elevated, insulin secretion is inhibited in the brain. An increased level of brain insulin induces an increase in glucose utilization that leads to an over-stimulation of the autonomic nervous system (ANS), while decreased levels of brain insulin decreases glucose utilization more commonly found in depression. It has been discovered that there are four glucose transporters operating in the brain2: glucose transporters (1-4). Glucose provides energy for the brain which crosses the blood brain barrier with the assistance of GLUT-1. GLUT-2 then transports glucose across cell membranes. GLUT-3 is involved in the expression of neurones and is found in the prefrontal cortex. GLUT-4, not originally thought to be a brain glucose transporter, has now been found in the pituitary, cerebellum, hypothalamus and medulla oblongata. GLUT-4 is influenced by insulin secretion and plays an important role in brain glucose metabolism. In order to understand the respective causes of mental illnesses it is necessary to understand the role of the inflammatory cytokines on brain insulin as well as the role of glucose transporters in the brain. Whenever these become dysregulated, it can trigger the onset of mental illness. But what exactly starts this train of events? PROPOSED CAUSES OF INSULIN DYSREGULATION. It has been hypothesised that exposure to high levels of vehicle emissions from cars, trains, trucks or planes, industrial emissions, pesticides used in farming such as Roundup, bacterial or viral illness and stress all play a role in the development of mental illness in genetically susceptible individuals. Such genetic susceptibility is found in families who develop various kinds of autoimmune diseases. The author conducted research (unpublished) into the prevalence of three autoimmune diseases: Diabetes, types I and II; Rheumatoid Arthritis and Cancer in families who had a family member formally diagnosed with schizophrenia. The study included the parents and two sets of grandparents, in which the autoimmune disease occurred. It was found that in all three disorders the prevalence of these conditions was 2-3 times higher than that found in the general population. Diabetes Type I & II and Rheumatoid Arthritis had a prevalence twice that of the general population while in Cancer, it was three times higher. This study served to confirm the role the immune system played in various mental illnesses. GENERALISED ANXIETY. The standard symptoms of Generalised Anxiety elaborated by Kaplan and Sadock (1985)3 in the Comprehensive Textbook of Psychiatry/V are as follows: Motor Tension 1 trembling, twitching, feeling shaky; 2 muscle tension, aches or soreness; 3 restlessness; 4 easy fatiguability. Autonomic hyperactivity 5 shortness of breath or smothering sensations; 6 palpitations or accelerated heart rate; 7 sweating or cold clammy hands; 8 dry mouth; 9 dizziness or light headedness; 10 nausea, diarrhoea or other abdominal distress; 11 flushes (hot flashes) or chills; 12 frequent urination; 13 trouble swallowing or ‘lump in throat’. Vigilance and scanning 14 Feeling keyed up or on edge; 15 exaggerated startle response; 16 difficulty concentrating or ‘mind going blank;’ 17 trouble falling or going to sleep; 18 irritability. CONCLUSION. In the Introduction it was mentioned that increased levels of brain insulin increased glucose utilization and, thus, overstimulation of the autonomic nervous system. It can therefore be argued that the above list of symptoms associated with Generalised Anxiety can be attributed to an increase in brain insulin in response to the above environmental conditions that, in turn, induces the release of the inflammatory cytokines. In the next article our attention will turn to Major Depression. REFERENCES: 1. Holden, R.J. (The role of brain insulin the neurophysiology of serious mental disorders Review.) Medical Hypothesis, (1999), 52 (3), 193-200. 2. McGowan, K.M., Long S.D., Pekala P.H. (Glucose transporters in the central nervous system homeostasis.) Pharmacy There. (1995), 66: 465-505.. 3. Kaplan, H. I. and Sadock, B. J. (Comprehensive Textbook of Psychiatry/V, Volume 1,) Williams and Wilkins (1989.) PREAMBLE: This series of articles by R J Holden, is a summary of numerous postdoctoral research papers on psychiatric disorders published in Medical Journals, when working in the Medical Research Unit, University of Wollongong 1992-1997.