HLA system, psychiatry and psychopharmacology

1. A number of antigens of the HLA system showed significant associations with clinical phenotypes of schizophrenia and manic depressive disorders. Even though we emphasize the need to consider these results with caution, we suggest that the findings now available indicate that the chromosomal regions which control the HLA system also contain the genetic material related to schizophrenia. On the other hand, although initial results have been encouraging, more work is needed before we can draw definite conclusions about the relationships between HLA antigens and the genetics of manic depressive disorders. All this recently acquired information is discussed and new lines for research are also suggested, including linkage studies in families, which might offer a more precise understanding of the genetic contribution to psychopathology. 2. Stressed also is the possibility that HLA determinants interfere with the interaction between neurotransmitters and/or psychotropic drugs and specific receptors. In this light, the clinical implications of HLA-A1 reactions to chlorpromazine and haloperidol, and of the HLA-A1 cross-reacting antigens are analyzed. Such studies are as yet very preliminary; however they perhaps help to clarify both the real biological roles of these antigenic membrane structures and the mechanisms by which psychotropic drugs interact with membrane receptors.