Schizophrenia is a chronic and disabling disorder with marked resource implications for health care services. The nature of the underlying disease process(es) remains obscure. The hypotheses that a neurochemical abnormality underlies some of the manifestations of schizophrenia is plausible: the most likely candidate is an increase in dopaminergic neurotransmission. There are also indications of organic changes in schizophrenic brain which may underlie some of the features of chronic schizophrenia. The present series of studies investigate these putative pathophysiological mechanisms by examining the secretion of anterior pituitary hormones in unmedicated patients with accurately diagnosed acute and chronic schizophrenia. The reasons for employing a neuroendocrine strategy are threefold. Firstly there is good evidence that hypothalamic neurotransmitters play a crucial role in the modulation of pituitary secretion: changes in these hormones may thus provide information on central neurotransmitter function. Neuroendocrine changes have been found in several neuropsychiatric diseases which are of potential clinical relevance. Finally there are several indications that a degree of hypogonadism is present in schizophrenic patients (pathological changes in the gonads reduced fertility, menstrual disorders and reductions in gonadotrophin secretion). Several neuroendocrine studies are reported in this thesis. Firstly the basal levels of several pituitary, thyroid and gonadal hormones have been investigated in acute and chronic schizophrenics and compared with controls. The rhythms of gonadotrophin, prolactin and growth hormone secretion have also been investigated (together with examination of the reproducibility of some of these measures). The hormonal response to synthetic hypothalamic releasing hormones has been studied in patients with chronic schizophrenia. In view of the interest in dopamine neurotransmission in schizophrenia the clinical and hormonal effects of dopamine antagonists and agonists in acute and chronic schizophrenics have been investigated. Pineal function in schizophrenia has also been examined and a paper discussing this bound into the thesis. Clinical associations have been examined and are emphasised throughout. The results demonstrate selective reductions in gonadotrophin secretion in a subgroup of chronic schizophrenics which are associated with a reduction in the frequency but not amplitude of LH secretory episodes. While this pattern of abnormal secretion appeared to be reproducible within individual patients, the administration of acute or chronic dopamine antagonists was associated with a return towards normal levels. This suggests that dopamine overactivity may be implicated in the genesis of these abnormalities and this cozitention is supported by the finding that gonadotrophin abnormalities were associated with low prolactin secretion. These patients exhibiting these abnormalities had the longest length of illness and the more frequent positive symptoms of schizophrenia (e.g. delusions and hallucinations). The growth hormone response to a dopamine agonist was reduced in chronic schizophrenic patients as a group and markedly so in a subgroup of patients, particularly those with negative symptoms which are characteristic of chronic schizophrenia and which are thought to have an organic basis. By contrast basal levels and rhythms of putitary hormones were normal in acute schizophrenia. Nevertheless several important relationships were established in this group e.g. between prolactin secretion and 1) the positive symptoms of schizophrenia and 2) the dose and blood level of DA antagonists These findings indicate that abnormalities of gonadotrophin secretion are unlikely to be of aetiopathological significance in schizophrenia but point to important relations between dopamine neurotransmission, clinical symptoms and anterior pituitary hormone secretion. In addition, several clinical observations of the effects of dopamine agonists on schizophrenic patients were made which, although effectively negative results, have important theoretical implications for schizophrenia research. The specificity, selectivity and significance of these results to the study of schizophrenia is extensively discussed in the text and possible areas of clinical relevance highlighted. The results strengthen the notion that there may be separate pathophysiological processes underlying different aspects of the schizophrenia syndrome and indicate that these hormonal changes may be useful markers of these processes. There are strong indications that there are abnormalities of peptide/dopamine interaction in the hypothalamus in schizophrenia. Some lines of future enquiry, based on these researches, are discussed which may help elucidate this complex and disabling disease
