68 for lithium poisoning except supportive treatment given for coma. How lithium works The mechanism of action of lithium is not understood at present, although several possibilities are being investi- gated. One theory is that it affects neurotransmitter activity (particularly noradrenaline (NA), serotonin, and dopamine (DA)) which may be present in unusual ratios in some types of mental illness. The 'catecholamine (NA and DA) hypothesis' has been shown recently to be an oversimplified explanation of depres- sion and manic depression 5. A second possibility is that certain amino acids in the brain (notably glutamic acid, aspartic acid, and 3,-aminobutyric acid) may be present in abnormal quantities in mood disorders, and be affected by lithium ion concentrations I. Acetylcholine, another neurotransmitter, is also being inves- tigated 6. Finally, it has been'suggested that human red cell membranes may contain a pump mechanism which transfers lithium and/or other ions out of the cell at abnormal rates 4. Behaviourai effects of lithium Lithium does not interfere with normal intellectual activity, nor does it impair consciousness or restrict the emotional range, as do some other types of treatment. Patients are fully able to experience normal emotions such" as joy, grief, and sexual desire. While conven- tional antipsychotic drugs (neuroleptics) may give a 'chemical straight-jacket' effect, patients on lithium report no such alteration; once maintenance levels are established the patient and his family can rarely tell the drug-controlled from the normal self. However, conventional netiroleptics begin to work immediately, while lithium takes five to ten days. For this reason many doctors in the case of a very assaultive or acutely paranoid manic patient may use the major tranquillizers traditionally used to calm manic states, at least in the beginning, until lithium begins to take effect. Chemically and clinically, lithium is entirely different from these major tranquillizers. Other uses for lithium carbonate Since it has been so spectacularly successful with manic depression, many researchers have begun to investigate the ability of lithium to affect other disorders. Psychotic premenstrual tension, chronic alcoholism, especially of the cyclical or (c) Elsevier/North-Holland Biomedical Press 1979 bingeing type, and adolescents with emotionally unstable character disorder, as well as prisoners with aggressive behaviour, show, according to some studies, improvements after lithium treatment. In addition, lithium has been claimed by a few to be beneficial in some non-episodic disorders such as tardivc dyskinesia, spasmodic torticullis, and Huntington's chorea. Who is suitable for treatment? Some patients, especially those with mild manic attacks, refuse lithium therapy because they feel their manic highs are valuable periods of creativity and produc- tivity. Any clinician must evaluate his patients with a view to their adaptation to the illness. If hypomania produces success and general well-being it may be therapeutically wiser to leave it alone and TINS - March 1979 to treat depressions, if they occur, with antidepressants. Reading list 1. Bed, S. and Clarke, D. D. (1975) In: F.N. Johnson (ed.), Lithium Research and Therapy, Academic Press, New York, pp. 425441. 2. Cade, J. F. J. (1949) Med. J. Aust. 36,349-352. 3. Fieve,R. R. (1973) In: S. Gershon and S. Shopsin (eds), Lithium: Its Role in Psychiatric Research and Treatment, Plenum,NewYork, pp. 317-350. 4. Meltzer, H. (1977)Psychiatric Research Society Abstracts, Feb. 1977, Salt Lake City, Utah. 5. Singer, 1. and Rotenberg, D. (1973) New Eng. J. Med. 289, 254-260. 6. Vizi, E.S., Illes, P., Ronai, A. and Knoll, J (1972) Neuropharmacology 11, 521-530. 7. Winokur, G. (1969) Manic Depressive Illness, C. V. Mosby, St. Louis. R. R. Fieve is Professor of Clinical Psychiatry and Chiefof Psychiatrie Research of Columbia Collegeof Physicians and Surgeons, and is Medical Director, Foundation for Depression and Manic Depression, 7 East 67th Street. New York, NY 10021. U.S.A. Immunogenetics of neurological diseases Jo61 J. F. Oger and Barry G. W. Arnason In thiJ article Jo~l Oger and Barry Arnason outline the relationships between immunology and genetics as they describe the histocompatibility system. They then continue to describe irregularities in the histocompatability system which occur in various neurological diseases, with special reference to multiple sclerosis, myasthenia gravis, and amyotrophic lateral sclerosis. All vertebrate species possess a gene complex, known as the major histocom- patability complex (MHC), the study of which has come into prominence in medical and biological research. The histocompatability system has been par- ticularly well characterized in mice, in which species it is designated as the H-2 complex, and in man, in which it is termed the HLA (for human leucocyte antigen) system. The MHC system of man has assumed importance in medical therapeu- tics, since individuals who match at the MHC will accept kidney or other tissue grafts from each other, whereas individu- als who mismatch will not. The import- ance of HLA for neurology, however, lies in a quite different arena. In mice it has been found that immune response (Ir) genes map in the MHC region, and for this reason histocompati- bility antigens can be employed as markers for Ir genesL Ir genes determine whether or not an immune response against any given foreign antigen, as for example a virus, will proceed in a vigorous fashion. They thus function, it is believed, as determining factors for development of those diseases in which immune responses are in play and also influence the severity of such diseases. Development of this concept in basic biology has led quite logically to study of HLA antigen profiles in man as markers for putative human Ir genes and, in turn, as markers for susceptibility to those diseases which are thought to have an infectious and/or an autoallergic basis 8. The impact of this approach on neurology has been profound. From a genetic perspective the HLA system is extremely complex. Four distinct loci which lie in close proximity to each other on chromosome 6 are currently recognized. A locus is defined as the position of a gene on the chromosome.