A prospective study of serum ghrelin levels in patients treated with clozapine.

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

Dopamine and serotonin function in untreated schizophrenia: clinical correlates of the apomorphine and d-fenfluramine tests.

This study examined the prolactin (PRL), adrenocorticotropin (ACTH) and cortisol responses to the direct DA receptor agonist apomorphine (APO) and the selective 5HT-releasing agent d-fenfluramine (d-FEN) in 20 untreated inpatients with DSM-IV schizophrenia and without a history of suicide attempt, compared to 23 hospitalized healthy controls. We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters. A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests (i.e. deltaACTH and deltacortisol) in the overall population and in schizophrenic patients. Pituitary-adrenal response to APO was lower in patients than in normal controls. Moreover, lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score. Lower pituitary-adrenal responses to APO (and to a lesser degree to d-FEN) differentiated paranoid from disorganized schizophrenic patients. Neither PRL suppression to APO, nor PRL stimulation to d-FEN were altered in schizophrenic patients. Our results suggest that decreased hypothalamic DA receptor activity (possibly secondary to increased presynaptic DA release) together with relatively decreased 5-HT tone characterize paranoid SCH, while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype.

Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes in plasma levels of GABA, HVA, and MHPG during treatment.

We demonstrated the effect of clonazepam (2 mg/day) on Meige syndrome in two schizophrenic patients under continuous treatment with antipsychotic drugs, and changes in the plasma levels of gamma-aminobutyric acid (GABA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in these cases. The plasma levels of HVA and MHPG during treatment with clonazepam were decreased in the responder, while not changed in the non-responder to clonazepam. A difference between the responder and the non-responder was not found in the plasma GABA levels. These results suggest that hyperactivities of the central dopaminergic and noradrenergic neurones are involved in the pathophysiology of Meige syndrome.

[Assays of arylsulfatase activity in psychotic patients. Review of the literature and results of a study of 22 patients]. / Dosages de l'activité de l'arylsulfatase chez les malades psychotiques. Revue de la littérature et résultats d'une étude chez 22 patients.

After a clinical and biological description of arylsulfatase A and metachromatic leucodystrophy, we present the results of a study of leucocyte arylsulfatase A in a population of 22 adult psychotic inpatients. The patients, clinically defined, filled the criteria of DSM III of schizophrenic disorders. All of them were treated by neuroleptics. None of these 22 patients showed a level of arylsulfatase A different from the range of 27 healthy adult controls. These results differ from those of most precedent studies of arylsulfatase A in "psychiatric populations". Some explanations of this difference are suggested. The concept of "purely psychiatric" form of adult metachromatic leucodystrophy is discussed.

Amino acid patterns in schizophrenia: some new findings.

Blood concentrations of various amino acids were measured in schizophrenic patients and control subjects. Significantly higher blood concentrations of glycine, glutamate, and serine were found in the schizophrenic patients. Glycine was abnormally elevated in subjects with paranoid or undifferentiated schizophrenia, but not in disorganized patients. Since glutamate, glycine, and serine play a complex role in the regulation of N-methyl-D-aspartate (NMDA) receptors, which are important in the control of normal cognitive processes, we hypothesized that the elevated levels of these amino acids might disrupt the normal functioning of NMDA receptors and might be involved in the pathophysiology of schizophrenia.

Secretion pattern of endogenous opioids in chronic schizophrenia.

Baseline plasma levels of beta-endorphin, beta-lipotropin, and ACTH were assayed in 37 patients with chronic schizophrenia: 24 men and 13 women, 28 with hebephrenic and nine with paranoid schizophrenia. None of the patients had received any medication for at least 10 days. The mean values of both opioids were significantly higher in the schizophrenic patients than in 21 age- and sex-matched control subjects. Insulin stimulation and dexamethasone suppression tests were given to eight of the patients, and the circadian rhythms of beta-endorphin, beta-lipotropin, ACTH, and cortisol were assayed in the same eight patients. Insulin stimulation, dexamethasone suppression test results, or circadian rhythmicity was impaired in seven of these eight patients.

[Controlled study of the disinhibiting effect of low doses of sulpiride in severe schizophrenic psychoses]. / Etude contrôlée de l'effet désinhibiteur de faibles doses de sulpiride dans les psychoses schizophréniques déficitaires.

This controlled study is designed to confirm the clinical impression concerning the dual therapeutic effect of sulpiride (disinhibitory effect at low doses and activity reducer at higher doses). When describing either 150 mg or 1,200 mg of sulpiride for hebephrenic patients, it seems that the benefits only occur in the patients prescribed the smaller dose. The correlation between dosage-plasma level-and beneficial result, is discussed.

Effects of clomiphene citrate administraiton on the hypothalamo-pituitary-gonadal axis of male chronic schizophrenics.

The clomiphene citrate stimulation test was performed in 16 adult male chronic hebephrenic schizophrenics (10 off therapy from 3 months to 1 year and six on therapy with phenothiazines or haloperidol) and in five normal controls, matched for age. Clomiphene citrate was given orally at a daily dose of 150 mg, divided into three doses, for 8 days. FSH, LH and testosterone levels were assayed before the administration of clomiphene citrate and after 4 and 8 days of treatment. Schizophrenics showed normal increase of FSH levels during the clomiphene administration, while LH and testosterone responses were blunted. Phenothiazines or haloperiodol had no effect on the test.

Prolactin secretion in chronic schizophrenia.

Basal prolactin secretion and its response to various stimuli have been studied in 20 chronic hebephrenic schizophrenics, 10 males and 10 females, aged 20-54 years. The duration of the disease varied between 4 and 30 years. Eight normal subjects from the hospital staff, four males and four females, matched for age, were used as controls. The patients had been off medication for 10 days in 17 cases, for 3 months in one case and for 1 year in two cases. The TRH stimulation test was done by giving 500 mug of TRH i.v., both to schizophrenics and controls. Schizophrenics and controls. Schizophrenics only were subjected to a 2-day therapy with chlorpromazine (4 mg/kg body weight per day orally), and therafter for 8 days to a combined therapy with chlorpromazine at the same dose plus 2-BRalpha-ergokryptine-mesilate (500 mg per day orally). Prolactin levels were assayed radioimmunologically in the basal condition, during the TRH stimulation test, after 2 days of chlorpromazine alone, and after 4 and 8 days of combined therapy with chlorpromazine plus 2-Br-alpha-ergokryptine-mesilate. The results obtained showed normal basal prolactin levels, significantly enhanced responses to TRH, normal increases after chlorpromazine alone, and substantial decreases after 2-Br-alpha-ergokryptine-mesilate. A possible relative catecholamine deficiency, related to the mental disease, is suggested to explain the results.

Histochemical changes in the blood cells of schizophrenic patients under pimozide treatment.

Chromatin structure and nucleohistone pattern were investigated histochemically in the neutrophils of 11 schizophrenics and 16 healthy controls. Compared to controls, all schizophrenic parents prior to medication showed a distinctly different histochemical pattern consisting of increased concentration and abnormal distribution of nucleohistones. This pattern has been attributed to an increase of arginine-rich histones in schizophrenics. Pimozide administration exerted a normalizing effect on the nucleohistone distribution pattern. These findings further support our view that genomic expression abnormalities may be related to schizophrenic illness.