Biochemical and Physiological Changes Associated with Schizophrenia.

Abstract

As our knowledge and clinical experience with phrenotropic drugs increases it is evident that agents such as reserpine, chlorpromazine, promazine, proclorperazine, perphenazine, and others make the disturbed psychotic more manageable but still leave him psychotic (48,130). The incidence of remissions following drug therapy appears no better than that following the myriad of more drastice somatic shock therapies. These results are not necessarily disappointing, for the widespread use of phrenotropic drugs as therapeutic adjuncts in psychiatry has strengthened the view that functions of the mind are the end result of an actively metabolizing brain. By giving fresh impetus to the search for possible physiochemical abnormalities in mental disease, the present nonspecific symptomatic drug therapies have already accomplished a great deal.Since the design of more specific drug treatments is dependent upon discrete knowledge of possible biochemical and physiological aberrations associated with mental disease, it is pertinent to the objectives of this conference to review critically the available evidence for such alterations. Both primary and secondary biochemical and physiological changes are of interest. Obviously it may be extremely difficult to distinguish between cause and effect. If one assumes that most mental disease has purely psychic etiological factors, it still follows that they will probably produce secondary physiological abnormalities; the psychosomatic literature provides many examples (40). The reverse is equally true; somatopsychic phenomena are well known. Physiological and biochemical alterations profoundly influence mental functions, as evidenced by the effects of hypoxia, hypoglycemia, and hypercapnia, and by such drugs as the hallucinogens LSD-25 and mescaline. Drug therapy, if rational, need not affect only primary physiochemical alterations, but may give symptomatic relief by modifying secondary disturbances. For example, an agent like amphetamine does not correct the primary psychopathology involving neurotic obesity but does curb the secondary increase in appetite.All physiological and biochemical changes in psychoses, if real, are of interest to the pharmacologist, for drugs might be designed that can affect either primary or secondary metabolic or physiologic disturbances. Presumably our present tranquilizers act to reduce secondary physiologic disturbances in the overreactive, vociferous, and hallucinating patient but do not affect his primary psychopathology.In 1895, Maudsley (132) wrote on insanity with excitement that: "The many diligent and elaborate chemical analyses of the urine which have been made by different inquirers in different countries, notwithstanding that the tabular exposition of them might fill a large volume, have failed to yield definite and constant results or to warrant any positive inference." This statement is equally true today for all types of insanity, but perhaps it should be qualified. Thus, in 1957, we can paraphrase Maudsley's remarks of 62 years ago and say t...