Catecholaminergic drugs in chronic schizophrenia.

The effect of dopaminergic-related and stimulatory drugs have been studied in chronic hebephrenic schizophrenics untreated with neuroleptic drugs. 6 patients received therapy of 2 g L-dopa + 200 mg carbodopa per day orally for 30 days, then placebo for 30 days. Following that 3 of the same patients received therapy of 2 g L-dopa + 200 mg carbodopa + 300 mg imipramine orally for 30 days, then placebo for 30 days. Following that the same 3 patients received 1 mg apomorphine s.c. for 15 days, then placebo for 15 days, then 1 mg apomorphine s.c. + 2 g L-dopa + 200 mg carbodopa per os daily for 15 days, then placebo for 15 days. The patients were examined psychologically by the Wittenborn Rating Scale, the Weigl Object-Sorting Test, and tests for verbal learning and verbal association, before and after each therapeutic trial. Levels of FSH, LH, testosterone and GH were assayed radioimmunologically before, in the middle of and after each course of therapy. 2 patients showed improvement in the affective-behavioural symptomatology during therapy, while the other 4, who had a more severe degree of mental deterioration and destruction, were unchanged. FSH and LH levels, very low under basal conditions, did not change under therapy. Testosterone was very low before therapy and increased in only 1 subject. Normal basal GH levels increased during therapy in some of the patients, but not constantly. The results obtained are discussed in relation to the catecholamine hypotheses of schizophrenia.

Glucose-insulin metabolism in chronic schizophrenia.

The present study deals with possible connections between the schizophrenic syndrome and alterations of the glucose-insulin metabolism. Data have been obtained in 18 patients, 9 males and 9 females, aged 22-62 years, suffering from chronic schizophrenia of 5-29 years duration. The patients were treated with Haloperidol for 30 days, 6 mg, i.m.p.d. to a total dose of 180 mg. The glucose metabolism was examined through a GTT (with a glucose load of 100 gr. per os), and an Insulin Tolerance Test (with 0.1 U/kg body weight). The insulin levels were examined under glucose load by the radioimmunological assay of Hales and Randle. The glycemic levels were examined under glucose load by an oxidative method. The psychopathological features were controlled by a Wittenborn Rating Scale. The metabolic and psychological examinations were done twice before the beginning of therapy, at 46 hrs. interval, then at 10-20-30 days of therapy. The results are probative for the presence of a chemical diabetes in a significantly high percent of patients. The significance of possible neurotransmitter impairments acting at both the biochemical and psychological levels is discussed.

Neuroendocrine effects of haloperidol therapy in chronic schizophrenia.

The neuroendocrine effects of haloperidol therapy have been examined in 62 male chronic schizophrenic patients, aged 16-62 years. The duration of the disease varied between 2 and 29 years. The patients were divided into 48 hebephrenics with onset of the disease at puberty, or immediately after puberty, and 14 paranoids with onset of the disease in adulthood. They received 6 mg i.m.p.d. of haloperidol, for 30 days, up to a total dose of 180 mg. The following hormonal variables were examined before therapy and at 10-20 and 30 days of treatment: total urinary gonadotropins, serum FSH and LH, GH response to insulin stimulation, ACTH reserve (Metyrapone test), total urinary 17-ketosteroids and 17-hydroxycorticoids before and after an ACTH stimulation test, serum testosterone, insulin response to glucose load, plasma thyroxine before and after a TSH stimulation test. The basic hormonal values revealed decreased secretion of total gonadotropins, FSH, LH, ACTH and testosterone, and increased insulin secretion. The haloperidol therapy seemed to stimulate the secretion of FSH, LH, total gonadotropins, ACTH and testosterone, up to normal or low-normal levels. No modifications were observed in the other hormonal variables. The significance of these results is discussed.

Growth hormone secretion in chronic schizophrenia.

The GH response to insulin hypoglycemia (insulin 0.1 IU/kg i.v.) was studied under basal conditions and during a course of haloperidol therapy in 19 chronic schizophrenics, 15 hebephrenics and four paranoids (ten men and nine women, age 16--53 years). Haloperidol was given for 30 days, at a daily dose of 6 mg i.m., and the GH response to insulin-induced hypoglycemia was tested twice, before, and 10, 20, 30 days following the initiation of the treatment. The psychopathological features were controlled daily by two psychiatrists and by the ward staff and by the use of a Wittenborn rating scale, rated at the same intervals as the hormonal assays. From the results obtained it appears that in schizophrenic patients, GH secretion and response to insulin stimulus are extremely variable and are unaffected by haloperidol treatment. On the basis of the results obtained, the neurotransmitter-neurohormone regulation of GH secretion in schizophrenics is discussed.

Blood flow and oxidative metabolism of the brain in patients with schizophrenia.

55 patients with schizophrenia were divided into three groups according to the clinical symptoms: (1) productive schizophrenias, i.e. patients with hallucinations, catatonic excitation and stupor; (2) paranoia and schizophrenia simplex, and (3) non-productive schizophrenias, i.e. patients with schizophrenic defects and hebephrenia. Total cerebral blood flow (CBF) and the rates of cerebral oxygen, carbon dioxide, glucose and lactate metabolism were investigated. Patients with productive schizophrenias displayed a significant increase in CBF (to an average of 101.4 ml/100 g min), CMR oxygen (to an average of 6.26 ml/100 g min) and CMR glucose (to an average of 12.11 mg/100 g min), i.e. CBF and CMR oxygen nearly doubled and CMR glucose more than doubled in comparison with normal findings. In patients with paranoia and schizophrenia simplex CBF and oxidative metabolism did not vary much and were within the normal range. Non-productive schizophrenias showed a significant decrease in CBF (to an average of 36.7 ml/100 g min), CMR oxygen (to an average of 2.20 ml/100 g min) and CMR glucose (to an average of 3.86 mg/100 g min) in comparison with both other groups of schizophrenias and the group of healthy young men. The results demonstrated variations in CBF and oxidative metabolism of the brain in patients with distinct types of schizophrenia. It was possible to find a correlation between the mental state of the psychosis on the one hand and CBF and metabolism on the other. The high CBF and metabolic rates of the brain in productive schizophrenias might be due to disturbances in the cerebral metabolism of biogenic amines.