RESUMO
Fatty acid compositions were determined in red blood cell (RBC) ghost membranes of schizophrenic patients before and after haloperidol withdrawal, as well as with age-matched normal male control subjects (n = 22). Patients on haloperidol (HD) received treatment in doses between 5 and 20 mg/day for at least 5 weeks (n = 24). Drug-free patients (n = 19) were free of all psychotropic medications for an average of 40 days. A highly significant decrease in the levels (nmol/ml packed RBC) of polyunsaturated fatty acids (PUFAs), particularly 18:2(n - 6) and 20:4(n - 6), was found in both HD-treated and drug-free patients. This decrease remained in those patients who had withdrawn from HD for more than 5 weeks (n = 10). Concomitantly, the percentage of saturated and monoenoic fatty acids to total fatty acids increased significantly in schizophrenic patients. The resultant fatty acid profile consequently lowers the unsaturation index (UI), which represents the average number of double bonds per fatty acid molecule, in RBC ghost membranes of schizophrenic patients. Furthermore, the decreases in UI were significantly correlated to the increases in "structure order" of RBC ghost membranes as measured by the steady-state fluorescence anisotropy (rs) in normal control and drug-free schizophrenic subjects. Therefore, it is likely that decreased levels of PUFAs in schizophrenic patients might result from a defective uptake of 18:2(n - 6) into RBC membrane phospholipids. Since fatty acid composition of membrane phospholipids affects the relative degree of membrane fluidity, the present results lend further support that RBC membrane dynamics are altered in schizophrenia.
Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos/metabolismo , Lipídeos de Membrana/metabolismo , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Adulto , Cromatografia Gasosa , Membrana Eritrocítica/efeitos dos fármacos , Ácidos Graxos Insaturados/metabolismo , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Valores de Referência , Esquizofrenia/tratamento farmacológico , Síndrome de Abstinência a Substâncias/sangueRESUMO
Fatty acid composition was quantitatively analyzed in RBC ghost membranes of 20 schizophrenic patients stabilized with haloperidol (5-20 mg/day) and of the same individuals after haloperdol (HD) withdrawal. The average days on medication and drug-free period were 52 and 40 days, respectively. No significant differences were demonstrated in levels (% or nmol/ml packed RBC) of polyunsaturated fatty acids (PUFAs) between HD-treated and drug-free patients. Similarly, no significant difference was found between relapsed and nonrelapsed schizophrenic patients, although the mean levels of 20:4 (n - 6), total PUFAs or fatty acid unsaturation index (FAUI) were consistently higher in nonrelapsers than in relapsers. On the other hand, the decreases in FAUI were significantly (r = -0.46, p = 0.04) correlated to the increases in psychosis rating which is consistent with our previous reported correlation between altered membrane fluidity and the severity of symptomatology. In addition, decreases in 18:2 (n - 6) but not 20:4 (n - 6) was significantly correlated to the increases in psychosis rating. The present results lend further support that decreased levels of RBC PUFAs in schizophrenic patients lie in an initial stage of PUFAs pathway, possibly a defective uptake of 18:2 (n - 6) into RBC membranes.
Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos/metabolismo , Lipídeos de Membrana/metabolismo , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Adulto , Deformação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica/fisiologia , Membrana Eritrocítica/efeitos dos fármacos , Ácidos Graxos Insaturados/metabolismo , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Síndrome de Abstinência a Substâncias/sangueRESUMO
Using the fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene), steady-state anisotropy (rs) values were determined in red blood cell (RBC) ghost membranes of schizophrenic patients before (n = 26) and after (n = 16) haloperidol withdrawal, and age- and sex-matched normal controls (n = 22). Patients on haloperidol were treated with doses between 5 and 20 mg/day for at least 5 weeks. Drug-free patients had been free of all psychotropic medication for an average of 36 days. The mean rs value of haloperidol-treated patients (0.2422 +/- 0.0076) was not significantly different from that of either the drug-free patients (0.2445 +/- 0.0092) or the normal controls (0.2383 +/- 0.0083). A significant increase (p = 0.037) in rs values, however, was observed in the drug-free schizophrenic patients as compared to that of the controls. Furthermore, the mean rs values of relapsed drug-free patients were significantly (p < 0.05) higher than in the same individuals on haloperidol treatment. Changes in rs values of drug-free patients were also significantly correlated with their increase in psychosis ratings (r = 0.74, p = 0.001). The 'structural order' of RBC ghost membrane, however, was not correlated with age, age of onset, daily haloperidol dose, plasma haloperidol levels, plasma cholesterol concentrations, or the duration of illness, haloperidol treatment or drug-free period. Thus, the present data demonstrate that RBC membrane fluidity is not affected by haloperidol treatment. Following haloperidol withdrawal, however, those patients with decreased RBC membrane fluidity, which correlated with increased psychosis, may be prone to relapse within 6 weeks.
Assuntos
Deformação Eritrocítica/fisiologia , Membrana Eritrocítica/fisiologia , Fluidez de Membrana/fisiologia , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Adulto , Anisotropia , Relação Dose-Resposta a Droga , Deformação Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/efeitos dos fármacos , Haloperidol/sangue , Haloperidol/uso terapêutico , Humanos , Masculino , Fluidez de Membrana/efeitos dos fármacos , Lipídeos de Membrana/fisiologia , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Recidiva , Esquizofrenia/tratamento farmacológico , Síndrome de Abstinência a Substâncias/sangueAssuntos
Ácido Homovanílico/sangue , Rememoração Mental/fisiologia , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Adulto , Biomarcadores/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Método Duplo-Cego , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Masculino , Rememoração Mental/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Recidiva , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Síndrome de Abstinência a Substâncias/sangue , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/psicologia , Escalas de WechslerRESUMO
CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI-LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia.
Assuntos
Proteínas de Transporte/líquido cefalorraquidiano , Tempo de Reação/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Sono REM/fisiologia , Adulto , Proteínas de Transporte/efeitos dos fármacos , Inibidor da Ligação a Diazepam , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polissonografia , Escalas de Graduação Psiquiátrica , Tempo de Reação/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/fisiologia , Esquizofrenia/tratamento farmacológico , Fases do Sono/efeitos dos fármacos , Fases do Sono/fisiologia , Sono REM/efeitos dos fármacosRESUMO
Chromogranin A (CgA) is a calcium binding protein and a precursor of modulatory peptides in the brain. We measured CgA-like immunoreactivity (CgA-LI) in cerebrospinal fluid (CSF) in 15 male schizophrenic patients (diagnosed by DSM-III-R criteria) after 3 nights of polysomnography. Patients had been drug free for at least 33 days. Our earlier report that CSF CgA-LI in schizophrenic patients correlated significantly with negative symptoms and ventricle-brain ratios, which have been related to slow wave sleep, raised the possibility that CgA-LI might relate to slow wave sleep. CSF CgA-LI was significantly correlated with stage 4 sleep and rapid eye movement latency. Whether these positive relationships between CSF CgA-LI and electroencephalographic sleep measures are specific for schizophrenia awaits further study.