Sustained remission in drug-free schizophrenic patients

The inability to determine which schizophrenic patients do not require maintenance medication is a significant gap in current knowledge. This report describes 23 largely chronic DSM-III schizophrenic patients who, after a period of inpatient treatment, sustained good outcome without maintenance antipsychotic medication over an average of 15 years. Retrospective study of these patients revealed that their distinguishing characteristics at admission included better premorbid social and occupational adjustment, higher levels of accrued psychosocial competence and acquired skills, fewer hebephrenic traits, and the preservation of affect (depressed mood). Hence, even within a largely chronic patient sample, classic predictors of good outcome may also be useful in predicting sustained remission without medication.     

Sleep analysis during drug-free weekends in chronic schizophrenic patients.

The authors made a polygraphic registration of the night sleep in a sample of 14 chronic schizophrenic patients who for several months (mean 8 months) have been on a stable, relatively low maintenance dosage of neuroleptics administered according to the drug-free weekend schedule (two consecutive drug-free days at the weekend). During this treatment none of them showed a relapse or deterioration (BPRS, CGI, and NOSIE rating scales were applied periodically). Their only complaint was of sleep deterioration during the drugfree weekend nights, especially during the second night. The polygraphic night-sleep pattern of each patient was studied during two consecutive weeks. No difference was found between the adaptation night on medication and the consecutive night on medication during the first week, and between the adaptation and readaptation nights on medication during two consecutive weeks. There was no difference in any sleep parameters between the nights on medication and the first drug-free nights. There was a signifcant difference in the total sleep time between the nights on medications and the second drug-free nights. No difference was found in any other sleep parameters in nights analysed as a blocks and in the distribution of NREM and REM stages in the first vs. the second half of the night when B3 was compared with A2. The practical implication is, that to avoid any change in nocturnal behavior it is preferable to withdraw the medication on two nonconsecutive days in the week. The evaluation of both daily and nocturnal behavior seems to be a useful tool in evaluating the first sign of the drug-withdrawal syndrome.     

Relationship between CSF noradrenaline levels, C-EEG indicators of activation and psychosis ratings in drug-free schizophrenic patients

ABSTRACT A significant increase of cerebrospinal fluid (CSF) noradrenaline (NA) levels, probably reflecting a rise of central noradrenergic activity, has been observed in a sample of acute schizophrenic patients as compared with a population of subjects without personal or family history of major psychoses. CSF NA levels have been found to be significantly correlated with computerized EEG (C-EEG) indicators of arousal (negative correlation with alpha relative activity and positive correlation with alpha barycentric frequency and beta relative activity in frontal and central leads). No significant relationship has emerged between CSF NA concentration and psychosis ratings on CPRS as well as platelet MAO activity. These findings seem to confirm the link between central noradrenergic hyperaciivity and the condition of enhanced arousal of the schizophrenic patient, although the role of this condition in the pathophysiology of schizophrenia (primary phenomenon or non-specific consequence of the stress related to the illness?) remains to be elucidated.     

Human platelet MAO in drug-free and medicated schizophrenic patients.

The authors compared platelet monoamine oxidase activity in drug-free chronic and acute schizophrenic patients, medicated chronic schizophrenic patients, and normal controls. A significant decrement in MAO activity was found only in medicated chronic schizophrenic patients. The possible mechanism for this finding is discussed.     

Conditional associative learning in drug-free schizophrenic patients

The performance on spatial and nonspatial associative learning tasks was tested in a sample of male drug-free DSM III-diagnosed schizophrenic patients and in a closely matched normal control group. Schizophrenics showed a worse performance on both versions of the task, but especially on the nonspatial one. A significant correlation was observed between some indices of the nonspatial task and the scores on two subscales (affective flattening and anhedonia) of the scale for the assessment of negative symptoms by Andreasen. These results are consistent with the hypothesis of a dysfunction of dorsolateral prefrontal cortex in schizophrenia and with the postulated linkage between such dysfunction and negative schizophrenic symptomatology.     

Reduced CSF neurotensin concentration in drug-free schizophrenic patients

The concentration of the tridecapeptide neurotensin was measured in CSF from 76 drug-free schizophrenic patients and 45 healthy controls. A highly significant difference was found between the two groups with lower concentration of neurotensin-like immunoreactivity in schizophrenic patients. Normalization of the lower concentrations was obtained in the same patients during ongoing neuroleptic treatment. The neurotensin concentrations in CSF was unrelated to sex, age, duration of the disorder or to previous neuroleptic treatment. Neurotensin levels did not differ between patients with or without a family history. A significant correlation was found between low neurotensin concentrations and decreased motor activity. No significant relationship was seen between the increment in CSF concentrations of neurotensin and clinical improvement during neuroleptic treatment. No significant correlation between CSF concentrations of neurotensin and HVA or 5-HIAA, major metabolites of dopamine and serotonin, respectively, could be demonstrated. However, in a limited number of the schizophrenic patients in this population, a significant correlation was seen between neurotensin and the noradrenaline metabolite MOPEG. The data support the hypothesis that certain schizophrenic patients may have a compromised CNS neurotensin system which might increase vulnerability for this disorder.     

Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients.

A low plasma prolactin concentration has been reported to be associated with an increased risk of subsequent relapse in patients with schizophrenia. Prolactin concentration was measured in samples from stable schizophrenic men who were outpatients just prior to neuroleptic withdrawal. No relationship between prolactin concentration and time to subsequent relapse was found. Prolactin concentration may predict time to relapse only in populations characterized by specific demographic features or medication history.     

Lateralized attentional deficits in drug-free and medicated schizophrenic patients

Performance on a cued reaction time (RT) task, theoretically linked to posterior and anterior neuroanatomical systems in the brain (Posner, M. I. et al., Science, 1988, 210, 1627–1631; Archives of General Psychiatry, 1988, 15, 811–821), was used to assess sensory orienting and maintenance of attention. In schizophrenic patients, Posner et al. found a lateralized abnormality in RT (longer RTs to uncued targets in the right visual field than in the left visual field), as did Maruff et al. (Neuropsychologia, 1995, 33, 1205–1223), but Strauss et al. (Journal of Psychiatric Research, 1991, 37, 139–146), among others, did not replicate this effect. However, the subjects in these studies differed in the percentage of schizophrenic patients taking neuroleptic medication at the time of testing and in the chronicity of the illness. In the present study, we used two groups of schizophrenic subjects to control for the use of neuroleptic medication. The lateralized abnormality in RT was observed in the drug-free group of schizophrenic subjects, but not in the group of drug-treated schizophrenic subjects.     

Recovery from schizophrenic psychosis

Knowledge of changes in patients' symptoms during hospitalization is crucial in planning treatment for acute psychotic exacerbation of chronic schizophrenia. Biweekly assessment of symptoms in 44 schizophrenic patients during the first 4 weeks of hospitalization showed that rapid recovery from psychotic symptoms occurred early in hospitalization; recovery from depression and anxiety was less complete. The rapid recovery in the first few weeks of hospital treatment supports the use of brief hospitalization for psychotic relapse. It is important to focus follow-up treatment on patients' relative lack of recovery in the hospital from depression and anxiety.     

Prolactin hyperresponsiveness to D-fenfluramine in drug-free schizophrenic patients: a placebo-controlled study.

BACKGROUND: Functional alterations in the central serotonergic system have been reported in schizophrenia but no conclusive data have been provided. In the present study, we investigated the prolactin (PRL) response to the selective serotonin (5-HT) releasing agent D-fenfluramine in both patients with schizophrenia and matched healthy subjects. METHODS: Sixteen drug-free schizophrenics and 16 healthy subjects were randomized in a double-blind neuroendocrine test to D-fenfluramine (30 mg p.o.) or placebo. Blood PRL and cortisol concentrations were determined by radioimmunoassay, while plasma levels of D-fenfluramine were measured by mass spectrometry. RESULTS: In schizophrenic patients, baseline plasma PRL levels were not different from controls, whereas plasma cortisol concentrations were significantly increased (p < .03). The PRL response to D-fenfluramine was significantly enhanced in patients as compared to matched control subjects (p < .005). Schizophrenics meeting Kane's criteria for previous nonresponse to typical neuroleptics exhibited a PRL response to D-fenfluramine significantly higher than non-drug-resistant patients (p < .04). No significant difference in plasma D-fenfluramine concentrations was observed between schizophrenic and healthy subjects. CONCLUSIONS: These findings suggest a serotonergic hypersensitivity in chronic schizophrenia. This alteration seems to be peculiar to those patients refractory to typical neuroleptics.     

Prolactin responses to haloperidol in drug-free and treated schizophrenic patients

Summary The prolactin response to 5 mg haloperidol i.m. was studied in 12 schizophrenic patients in a drug-free state and after a month treatment with haloperidol, as a possible index of dopamine receptor sensitivity and occupancy. Blood samples were taken at times 0, 60, 90 and 120 minutes. The increase in PRL observed in the drug-free state disappeared after drug treatment. The PRL plasma levels after treatment with 60 mg haloperidol per os were higher than the maximal PRL responses after 5 mg i.m. The increases in baseline PRL caused by the treatment correlated positively to the reduction in the BPRS score. The test was also performed in a group of 11 patients chronically treated with haloperidol during a daily dose of 60 mg, and 15 days after reduction of the dose to 30 mg. PRL increases after 5 mg haloperidol i.m. were observed only after reduction of the dose. It is suggested that the prolactin response to haloperidol is an index of the occupancy of receptors that are involved in the PRL releasing mechanisms, and could be used to verify their blockade by the neuroleptics, especially in patients that do not respond positively to drug treatment.     

Early diagnosis of schizophrenic psychosis

Schizophrenia is an illness characterized by its syndromic polimorphism and a global impairment of personality traits, that means a lot of suffering for patients and their families. Lately, under the framework of the "neurodevelopmental theory of schizophrenia", the scientific community has paid attention to the need of detecting the illness before onset or as soon as possible. The study of premorbid personality traits, as "schizotaxia" or schizoid or schyzotypal personality, altogether with the study of the so called "basic symptoms" an premorbid states are designed to detect at risk subjects. The need of not waiting until acute onset syndromes in an attempt to more early interventions, due to the fact that there is strong evidence about the existence of early symptoms which proper identification will allow, in the future, to identify subjects at risk an earlier interventions. In this paper we will review only some of the great number of papers recently published on the subject.     

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 O1, O2, Oz, C3 and C4 to combined ear reference (A1--A2). 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.     

Predicting outcome in schizoaffective psychosis

Predictors of long-term outcome are identified for 68 patients with schizoaffective psychosis from the Chestnut Lodge Follow-up Study. Two dimensions regularly predicted better outcome: better developed premorbid instrumental skills and fewer typically schizophrenic symptoms.