INTRODUCTION One current theory on the etiology of schizophrenia involves a developmental brain abnormality. This brain dysfunction may result from a faulty maturational pro- cess occurring in the CNS some time during infancy and/or adolescence. This may result from an imbalance in the neurotransmitters. Historically, it has been accepted that an excess of the neurotransmitter dopamine results in schizophrenia. Indirect evidence for the role of dop- amine in schizophrenia comes from the observation that substances like amphetamines exacerbate the schizo- phrenic psychosis. Furthermore, in normal individuals, these substances may induce a psychotic state similar to that found in paranoid schizo-phrenics (1). Direct evidence comes from the fact that dopamine blockers have been shown to alleviate schizophrenic symptoma- tology in both schizophrenics and in normal individuals who have had psychotic states induced through the use of amphetamines (1). While this phenomenon has been used in support of the dopamine hypothesis, it can also be used to negate its importance in producing schizophrenia. More specifically, the dopamine hypothesis is limited because dopamine antagonists have limited results in ameliorating the symptoms of schizophrenia. Currently, we rely on neuroleptics to help schizophrenic patients overcome their symptoms but, more often than not, these medications only reduce positive symptoms, leaving the negative symptoms intact (2). HISTAMINE Current research indicates that the neurotransmitter histamine also plays an important role in the formation of schizophrenia. Although only recently acknowledged, there actually appears to be much more evidence for the etiological role of histamine rather than dopamine. Chronister and DeFrance (6) noted that schizophrenics show attentional deficits that may result from an im- balance in dopamine and histamine modulation of afferent hippocampal activity in the nucleus accumbens. As a matter of fact, dopamine effects are mimicked by a decrease in histamine receptors or an increase in hist- amine degradation. Both allow for a relative increase in dopamine. It may be that all of the evidence for dopamine may be a byproduct of an imbalance in the histaminergic system (3,4). Research in this area was done as early as 1938. Re- searchers at this time found that subcutaneous injections of histamine produced favorable therapeutic responses in schizophrenic patients (5–7). This finding suggests that there may be a relationship between dopamine and histamine. Recent research has indicated that there in fact does exist a direct relationship between dopamine and histamine. One study by Alvarez (8) demonstrated that antipsychotic drugs increase plasma levels of prolactin in conscious rats. Prolactin and dopamine are mutual antagonists, whereas prolactin and histamine have an agonistic relationship. This is important because prolactin may also be elevated by histamine in the area of the anterior hypothalamus. Several studies have supported the idea that histamine metabolism is affected in schizophrenia. A 1965 study by Yamada and Takumi found that small doses of histamine were capable of alleviating the effects of lysergic acid Medical Hypotheses (1999) 52(1), 37–42 © 1999 Harcourt Brace & Co. Ltd Article No. mehy.1997.0671 Histamine and prostaglandins in schizophrenia: revisited E. Heleniak (deceased), 1 I. O’Desky 2 1 Late of 811 Madison Avenue, Dunellen, NJ, USA 2 Institute For Behavioral Awareness, Springfield, NJ, USA Summary It has long been accepted that schizophrenia is primarily a physical illness resulting from a chemical imbalance in the brain. This paper will review evidence supporting the hypothesis that histamine and prostaglandins are both linked and primary in the etiology of schizophrenia. Furthermore, their etiological significance supersedes the role of dopamine as a primary causative factor. Received 8 December 1993 Accepted 4 January 1994 Correspondence to: Ilyse O’Desky PsyD, Short Hills Associates in Clinical Psychology, 28 Millburn Avenue, Springfield, NJ 07081, USA (Phone: +1 973 467 9333; Fax: +1 973 467 1145) 37