Drug-free Chronic Schizophrenic Patients Research Articles

Circadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormones, and cortisol in schizophrenia

Changes in the circadian rhythmicity in vital signs, catecholamines, thyroid hormones, and cortisol have been observed in psychiatric disorders, most notably in depression. With respect to schizophrenia, the literature is scanty. We report here on the circadian parameter estimates of the vital signs, epinephrine, norepinephrine, triiodothyronine, thyroxine, thyroid stimulating hormone, and cortisol in the blood of 34 healthy subjects, 89 drug-free schizophrenic patients, and 25 neuroleptic-treated schizophrenic patients. The analyses are based on the cosine model to fit the experimental data. The circadian profiles of heart rate, blood pressure, and oral temperature are similar among schizophrenic patients and healthy subjects. Neuroleptic-treated patients have significantly higher MESORs (the daily mean) of serum norepinephrine and epinephrine than healthy subjects. The TSH MESOR is significantly lower in schizophrenic patients; the MESOR of triiodothyronine also shows a tendency to be nonsignificantly lower in schizophrenic patients compared with control subjects. The circadian serum thyroxine and cortisol profiles are similar in the three groups. The data show that the circadian profiles of vital signs in drug-free chronic schizophrenic patients who are not chronically hospitalized are similar to those of healthy subjects and that the increase in serum catecholamines and the apparent lowering in some thyroid indices might induce a down-regulation in the noradrenergic receptor system that could contribute to the pathophysiology of schizophrenia.

Resting and thrombin-stimulated cytosolic calcium in platelets of patients with alcoholic withdrawal, bipolar manic disorder and chronic schizophrenia

Cytosolic calcium concentration ([Ca 2+] i) in platelets during resting state and when stimulated by thrombin were measured in 7 alcoholic dependent patients in the state of withdrawal (AW) who were receiving diazepam, 7 bipolar manic patients (BM) who were receiving haloperidol, 15 drug free chronic schizophrenic patients (CS) and 26 normal controls (NC). Resting [Ca 2+] i in these groups were quite similar at (mean ± SEM) 112 ± 20 nM, 127 ± 18 nM, 103 ± 16 nM and 106 ± 8 nM respectively. Increase in platelet [Ca 2+] i in response to 0. l U/ml thrombin was expressed as A[Ca 2+] i and its percentage over resting [Ca 2+] i as %[Ca 2+] i Both Δ[Ca 2+] i and %[Ca 2+] i were significantly higher (p = 0.006 and 0.0045 respectively, ANOVA, Waller-Duncan) in AW (433 ± 71 nM, 417 ± 58%) than the other groups: NC (223 ± 25 nM, 225 ± 23%), BM (309 ± 38 nM, 260 ± 31%), and CS (261 ± 34 nM, 280 ± 29%) respectively. In vitro incubation of platelets from NC with diazepam or haloperidol did not affect the resting [Ca 2+] i and %[Ca 2+] i. The enhanced [Ca 2+] i response to thrombin in platelets of AW is unlikely to be due to diazepam. It may indicate an abnormality in platelets during the withdrawal phase. Treatment with haloperidol resulted in slightly higher [Ca 2+] i in platelets of BM. Platelet [Ca 2+] i in drug-free CS was not different from NC.

Early antipsychotic response to resumption of neuroleptics in drug-free chronic schizophrenic patients

Early antipsychotic response to resumption of neuroleptics in drug-free chronic schizophrenic patients

Neuropeptide Y like immunoreactivity in schizophrenia: Relationships with clinical measures

Neuropeptide Y-like immunoreactivity (NPY-li) was measured in CSF of 35 drug-free chronic schizophrenic patients. Compared to a group of drug-free controls, CSF NPY-li was significantly higher in these patients. CSF NPY-li decreased with age and longer duration of illness. Measures of structural brain abnormalities on CT scans were significantly associated with lower CSF NPY-li. Relationships between NPY-li and schizophrenic behavior, i.e. positive symptoms, were observed only in the clinically stable (nonrelapsed) drug-free patients. In 31 of the patients CSF was obtained before and after withdrawal from haloperidol maintenance treatment. This withdrawal from haloperidol treatment was associated with a significant increase in CSF NPY-li. There was no significant difference in CSF NPY-li between patients who did and those who did not relapse within 6 weeks following haloperidol withdrawal. The present findings suggest a relationship of CSF NPY-li with various aspects of schizophrenia.

Neuropeptide Y-like immunoreactivity in schizophrenia: Relationships with clinical measures

Neuropeptide Y-like immunoreactivity (NPY-li) was measured in CSF of 35 drug-free chronic schizophrenic patients. Compared to a group of drug-free controls, CSF NPY-li was significantly higher in these patients. CSF NPY-li decreased with age and longer duration of illness. Measures of structural brain abnormalities on CT scans were significantly associated with lower CSF NPY-li. Relationships between NPY-li and schizophrenic behavior, i.e. positive symptoms, were observed only in the clinically stable (nonrelapsed) drug-free patients. In 31 of the patients CSF was obtained before and after withdrawal from haloperidol maintenance treatment. This withdrawal from haloperidol treatment was associated with a significant increase in CSF NPY-li. There was no significant difference in CSF NPY-li between patients who did and those who did not relapse within 6 weeks following haloperidol withdrawal. The present findings suggest a relationship of CSF NPY-li with various aspects of schizophrenia.

Eye-blinking and cerebral ventricular size in chronic schizophrenic patients

Spontaneous eye-blinking, a possible measure of central dopaminergic activity, was studied in 55 drug-free chronic schizophrenic patients subdivided by cerebral ventricular size. Blink rates were higher in schizophrenic patients than in normal control subjects, regardless of cerebral ventricle size. Neuroleptics lowered blink rates in patients with normal ventricles but did not affect blink rates in patients with large ventricles. Insofar as blinking is a dopaminergic parameter, these findings suggest that the dopamine hypothesis of schizophrenia is most relevant in patients with normal ventricles.

Plasma prolactin concentrations and psychopathology in chronic schizophrenia.

Plasma prolactin concentrations in 17 drug-free chronic schizophrenic patients correlated inversely with ratings of their psychopathology. An inverse relationship between psychotic symptoms and plasma prolactin concentrations was particularly clear in patients with normal cerebral ventricular size as determined by computed tomography. The psychosis-prolactin relationship did not hold for schizophrenic patients with large ventricular size. These data suggest that the degree of psychosis is related to dopaminergic activity insofar as this is reflected by plasma prolactin concentrations, especially in schizophrenic patients with normal ventricular size. These findings lend further support to the hypothesis that ventricular size is a meaningful factor in subtyping chronic schizophrenic patients.

Urinary neurotransmitter metabolites in drug-free chronic schizophrenic patients measured by gas chromatography selected positive ion monitoring.

The free urinary metabolites, homovanillic, indoleacetic and 5-hydroxyindoleacetic acid were measured in 24 h urines obtained from seven highly selected drug-free chronic schizophrenic patients and seven mentally normal control subjects on a low amine diet. Gas chromatography selected ion monitoring of silylated extracts was used to assay each metabolite using its own deuterated form as an internal standard. In the electron impact mode the positive ion fragments used to quantitate the amount of each metabolite in the urine were, respectively, m/z 209/211 for homovanillic acid, 319/321 for indoleacetic acid and 290/292 for 5-hydroxyindoleacetic acid. It was found essential that each compound be assayed using its own deuterated derivative as the internal standard. When expressed per mg creatinine, the homovanillic and 5-hydroxyindoleacetic acid levels of the chronic schizophrenic patients were in the normal range, but indoleacetic acid was slightly and statistically significantly higher, p = 0.01.

Comparison of the visually evoked response in drug-free chronic schizophrenic patients and normal controls

Thirteen cooperative male drug-free chronic schizophrenic patients, and 11 mentally normal male controls were studied. The VER was recorded from scalp leads O 1, O 2, O z, C 3 and C 4 to combined ear reference (A 1A 2). The stimulus was an unpatterned flash of single intensity. Compared to normal controls, there were no consistent differences in wave peak latencies or amplitudes for chronic schizophrenics in any brain area tested. When the chronic schizophrenic patients were separated on the basis of high and low tryptophan uptake, using the Frohman-Gottlieb criteria, the high uptake group exhibited normal VERs while in the occipital regions the low tryptophan uptake group exhibited prolonged latencies and an increased amplitude for wave V when compared to normals. From BPRS scores the high tryptophan subgroup indicated a greater degree of psychopathology than the low tryptophan subgroup. The results obtained do not support an indole hallucinogen hypothesis for process schizophrenia.

In vitro half-life of 14-C-tryptamine in whole blood of drug-free chronic schizophrenic patients.

The authors found higher in vitro 14C-tryptamine half-lives in the blood of 10 drug-free chronic schizophrenic patients than in the blood of 13 mentally normal control subjects. This finding was negatively correlated for both groups with platelet MAO activity. Repeated determinations of in vitro 14C-tryptamine half-lives over a period of 5 months were positively correlated for the patients, although some blood samples showed statistically significant variability.

Gas chromatographic-mass spectrometric identification of N:N-dimethyltryptamine in urine samples from drug-free chronic schizophrenic patients and its quantitation by the technique of single (selective) ion monitoring

The identification of N:N-dimethyltryptamine in urine samples of drug-free chronic schizophrenic patients is confirmed by gas chromatography-mass spectrometry of both the free tertiary amine and the trimethylsilyl derivative. A quantitative method using single ion detection (m/e 58) is described. Urine samples from the six subjects were positive for bufotenin by both thin-layer chromatography and gas chromatography-mass spectrometry. Samples from three of the six subjects were also positive for N:N-dimethyltryptamine by both methods. Comparable results obtained by thin-layer chromatography and by single ion detection during gas chromatography-mass spectrometry showed that the levels of N:N-dimethyltryptamine in 24-hr urine samples were less than 1 μg.