Lower prolactin bioactivity in unmedicated schizophrenic patients.

In previous work, prolactin (PRL) abnormalities of a lower bioassay (BA) to radioimmunoassay (RIA) ratio were found in schizophrenic patients. This line of research was extended in seven male patients with schizophrenia who were neuroleptic-free; seven male control subjects were also studied. PRL values were assessed by RIA and Nb(2) BA techniques. The schizophrenic group had a significantly lower PRL BA as compared to normal controls and a lower PRL ratio of BA/RIA. The lower ratio is consistent with an earlier finding and suggests that schizophrenic patients have different molecular forms of PRL than control subjects. This difference could be due to a disordered tuberoinfundibular dopamine system or the long-term effects of neuroleptic medications.     

EEG coherence in unmedicated schizophrenic patients

We have recently shown that electroencephalogram (EEG) coherence data recorded with common reference methods, including those obtained from schizophrenics, are confounded by power and phase effects. Three published reports using bipolar recordings found that EEG coherence was higher in schizophrenics; however, only medicated patients were studied. To extend these findings, we measured EEG coherence from bipolar EEG recordings in unmedicated schizophrenics (n = 10), affective disorder patients (n = 8), and normal controls (n = 13) during resting and task conditions. Seven schizophrenics were restudied after a period of neuroleptic treatment. Schizophrenics had higher across-task interhemispheric (p less than 0.05) and intrahemispheric (p less than 0.04) coherence in the theta band and tended to have higher intrahemispheric alpha coherence (p less than 0.08). Medication treatment was associated with clinical improvement and increases in spectral power, but not with changes in coherence values. These results confirm those obtained by earlier investigations and suggest that increased coherence reflects the presence of anomalous cortical organization in schizophrenics rather than medication effects or transient states related to acute clinical disturbance.     

Luria-Nebraska performance and symptomatology in unmedicated schizophrenic patients

Recent attempts at subgrouping schizophrenia have emphasized negative symptoms (e.g., blunted affect, emotional withdrawal), and several works have suggested that patients with negative symptoms show greater cognitive deficits and structural brain abnormalities. However, many of these studies have relied on screening devices or single measures of neuropsychological performance. Accordingly, the present study used the Luria-Nebraska Neuropsychological Battery (LNNB) in assessing 38 unmedicated inpatients with a diagnosis of schizophrenia. The results found no relationship between LNNB performance and symptom ratings derived from clinical interviews using the Brief Psychiatric Rating Scale. The findings show that cognitive performance may be unrelated to symptomatology when a complex battery type test is used.     

Cytokine production in unmedicated and treated schizophrenic patients

Recent findings have strengthened the hypothesis that immunological dysfunctions may contribute towards the multifactorial pathogenesis of schizophrenia. The validity of these findings is questioned by the fact that most studied subjects have received potentially immunomodulatory medication upon investigation. In order to rule out such confounding effects, 24 initially unmedicated acutely ill schizophrenic patients were studied immunologically and psychiatrically (PANSS) before and during 4 weeks of neuroleptic treatment. The production of IFN-gamma was decreased upon admission and after 2 weeks of treatment compared to matched healthy controls. No differences in IL-2 and IFN-gamma production between unmedicated and medicated states were observed. These results do not support the notion that neuroleptic medication in vivo might influence TH1 cytokine production in schizophrenia.     

Cabergoline-induced psychotic exacerbation in schizophrenic patients

INTRODUCTION: Hyperprolactinemia is a well-recognized side effect of antipsychotic treatment. Cabergoline, a dopamine agonist, has been introduced on the market to treat hyperprolactinemia, even secondary to antipsychotic use. CASE REPORT: In this article, we described two schizophrenic patients who received cabergoline to treat their antipsychotic-induced hyperprolactinemia and developed a subsequent psychotic exacerbation. The first patient received amisulpride as antipsychotic medication, and the second one took risperidone and fluoxetine for her psychotic and depressive symptoms, respectively. Both patients improved significantly their psychotic symptoms in 1 week without changing their former antipsychotic regimens. DISCUSSION: To the best of our knowledge, we found no previous report of cabergoline-induced psychotic exacerbation in schizophrenic patients who received antipsychotics. We brought up questions whether schizophrenic patients on amisulpride or with the addition of fluoxetine may have higher risk to experience psychotic worsening. We also highlighted the possible role of dose-dependent nature in cabergoline-induced psychotic exacerbation, suggesting that the single starting dose of 0.5 mg or higher might be unsafe in schizophrenic patients. CONCLUSION: These cases suggest that cabergoline, like other dopaminergic agents, should be used with caution in psychotic patients and the dose should be as low as possible.     

EEG coherence in unmedicated schizophrenic patients: topographical study of predominantly never medicated cases.

Electroencephalographic (EEG) power and coherence were compared in 11 unmedicated schizophrenics (including 9 never mediated patients) and in 15 normal controls. There was no significant difference in power between the two groups. However, interhemispheric coherence between O1-O2 was higher in the schizophrenics in the delta and beta bands, and interhemispheric coherence between T5-T6 was higher in the delta band. These results suggest that coherence is more sensitive than power for comparison of these two groups, and that cerebral function is less lateralized in schizophrenics.     

Polyunsaturated fatty acid levels in red cell membranes of unmedicated schizophrenic patients.

There are several reports of reduced levels of polyunsaturated fatty acids (PUFA), particularly arachidonic acid (AA) and docosahexaenoic acid (DHA), in membrane phospholipid from various tissues including red blood cells (RBC) taken from schizophrenic patients. However, reports have not been entirely consistent and most studies have been confounded by the potential effects of environmental factors including antipsychotic medication and diet. We measured PUFA levels in RBC from two separate groups of unmedicated patients and control subjects from India and Malaysia, populations which have substantial differences in diet. We found no significant difference in levels of AA between patients and control subjects in either population. Levels of adrenic acid were significantly reduced, and levels of DHA significantly increased in both clinical populations. However, diet-related differences in DHA between the populations from India and Malaysia were much greater than differences between schizophrenic patients and controls. It is concluded that reduced RBC membrane levels of AA and DHA are not pathognomic of schizophrenia but that variations in cell membrane fatty acid levels are an epiphenomenon which may reflect underlying abnormalities of phospholipid and fatty acid metabolism and their interaction with environmental factors including medication and diet.     

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.     

Backward masking in bipolar affective disorder.

1. When an informational stimulus, the target, is followed closely in time by a non-informational stimulus, the mask, the visual system's processing of the informational stimulus is disturbed. This disturbance is known as backward visual masking. 2. Transient and sustained visual pathways detect different characteristics of a visual stimulus, at different times in early visual information processing, and have unique anatomic distribution with regard to retinal origin, thalamic and cortical projections. 3. Backward masking occurs by two mechanisms. Interruption occurs when activity in the transient channels of the mask disrupt activity in the sustained channels of the target. Integration occurs when activity in the sustained channels of the mask disrupt activity of the sustained channels of the target. 4. Characteristics of the mask--energy, location, or the time presented after the target--can be altered to enhance interruption or integration. Interruption is a bell-shaped function of, and integration is an exponential function of, visual performance and interstimulus interval. 5. An impairment in backward masking is present in bipolar subjects during manic episodes, is not related to the presence of psychotic symptoms, and persists when mania resolves. Lithium appears to have a detrimental effect on backward masking.     

Functional motor asymmetries correlated with clinical findings in unmedicated schizophrenic patients

Motor asymmetries were investigated in 28 unmedicated schizophrenic in-patients and 32 healthy controls. Of the patients, who were assessed as right-handers by a handedness questionnaire, 46.4% changed their motor laterality in at least one part of the tapping test series, probably because of a decrease of functional hemispheric asymmetry. These patients were characterized by more pronounced psychotic symptoms than those who did not change motor laterality. According to the tapping frequency, two groups of patients could be distinguished: the high- and the low-frequency group. In both groups certain tapping data could be correlated with characteristic clinical features. While the findings in the high-frequency group point to an enhanced activation level of the right hemisphere and appear to be correlated with the onset of positive symptoms and better prognosis, the findings in the low-frequency group may be a reflection of a disturbed function of the left frontal region and seem to be correlated with a gradual chronic development of predominant negative symptoms with worse prognostic implications.     

Reduced oscillatory gamma-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing.

OBJECTIVE: Integration of sensory information by cortical network binding appears to be crucially involved in target detection. Studies in schizophrenia using functional and diffusion tensor neuroimaging, event-related potentials and EEG coherence indicate an impairment of cortical network coupling in this disorder. Previous electrophysiological investigations in animals and humans suggested that gamma activity (oscillations at around 40 Hz) is essential for cortical network binding. Studies in medicated schizophrenia provide evidence for a reduced gamma activity in the context of auditory stimulus processing. This is the first investigation of oscillatory activations in the gamma-band in an auditory oddball paradigm in unmedicated schizophrenic patients. METHODS: EEG gamma-band responses (GBRs) of 15 drug-free schizophrenic patients and 15 age- and gender-matched healthy controls were compared. A wavelet transform based on Morlet wavelets was employed for the calculation of oscillatory GBRs. RESULTS: In response to standard stimuli, early evoked GBRs (20-100 ms), which are supposed to reflect auditory cortex activation, did not show significant group differences. However, schizophrenic patients showed reduced evoked GBRs in a late latency range (220-350 ms), particularly after target stimuli. This deficit occurred over right frontal scalp regions. Furthermore, significant correlations were observed between oscillatory GBRs and clinical parameters in schizophrenic patients. CONCLUSIONS: The results are consistent with a relative preserved stimulus processing in the auditory cortex as reflected by the early GBR. The reduced late GBR is compatible with an abnormal interaction within a frontal lobe network, as was postulated by previous neuroimaging studies. SIGNIFICANCE: The present study provides evidence for disturbed processing within frontal cortical regions in unmedicated schizophrenic patients as indicated by reduced evoked EEG GBRs.     

Nerve growth factor in never-medicated first-episode psychotic and medicated chronic schizophrenic patients: possible implications for treatment outcome

Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predominantly cholinergic neurons in brain development, and neuronal survival following brain injury, which reflect in cognitive performance. Wide ranges of neurodevelopmental abnormalities have been reported in schizophrenic patients, who also show poor cognitive performance. We report plasma NGF levels in never-medicated first-episode psychotic (FEP; N=24) and chronic medicated schizophrenic patients (N=24). NGF levels were determined in plasma by Enzyme-Linked ImmunoSorbent Assay (ELISA). Plasma NGF levels were significantly lower in both FEP and medicated chronic patients as compared to normal subjects (P<0.001). However, NGF levels were significantly higher in chronic schizophrenic patients, which were treated with antipsychotics as compared to FEP (P<0.05). Moreover, NGF levels in chronic patients treated with atypical antipsychotics were markedly higher as compared to patients treated with typical antipsychotics (P<0.05). Lower NGF levels in FEP patients at the onset of psychosis may have implications for the neurodevelopmental abnormalities. However, higher NGF levels in chronic patients treated with atypical antipsychotics may have implications for the treatment outcome.     

Comparative remission rates of schizophrenic patients using various remission criteria

Rationale

New standardized criteria for remission in schizophrenia were presented in 2005 which need to be examined in regard to their significance for clinical trials.

Objectives and methods

Data of six antipsychotic drug trials (n = 2463) were analyzed by evaluating the proportion of participants who meet the new remission criteria, their symptomatic components, other criteria for remission and simple response-measures (at least 50% Brief Psychiatric Rating Scale (BPRS) reduction and an at least 50% PANSS reduction or a CGI-severity score of “mild or better”).Results: A total of 23.3%/27.2% (last-observation-carried-forward (LOCF)/completer analysis (CO)) of the patients with positive symptoms at baseline met the severity criteria of remission at 4 weeks, 10.5%/20.3% (worst case/CO) met the severity and time criteria at 28 weeks (three studies) and 10.9%/32.4% (worst case/CO) met the severity and time criteria at 52 weeks (one study). At 4 weeks 4.5%/5.5% (LOCF/CO) met the severity criteria when a more stringent severity threshold of “very mild or better” was applied. Absence of symptoms was attained only sporadically. The psychotic symptoms component was met by fewer patients than the negative component. The criteria were more stringent than “at least 50% BPRS reduction” and “CGI-severity score not more than mild” and – for the long-term results – than “at least 50% PANSS reduction”. In the short-term analysis, the criteria were less stringent than “at least 50% PANSS reduction”.

Conclusions

The applicability of the severity component of the new criteria in clinical trials was confirmed. The time criterion remains difficult to evaluate.     

Forward and backward visual masking in unaffected siblings of schizophrenic patients.

BACKGROUND: Visual masking tasks assess the earliest stages of visual processing. This study examined visual masking performance for forward and backward masking tasks in siblings of schizophrenic patients and healthy comparison subjects. METHODS: A staircase method was used to ensure that unmasked target identification was equivalent across subjects to eliminate differences due to discrimination of simple perceptual inputs. Four computerized visual masking tasks were administered to 43 siblings of patients and 42 normal comparison subjects. The tasks included: 1) locating a target; 2) identifying a target with a high-energy mask; 3) identifying a target with a low-energy mask; and 4) a paracontrast/metacontrast procedure with nonoverlapping target and mask. RESULTS: Across masking conditions, there was a significant group by forward/backward interaction, meaning that siblings showed a larger difference from control subjects in backward versus forward masking. This group difference was more pronounced in the location condition. CONCLUSIONS: These results support the theory that visual masking procedures may be indicators of vulnerability to schizophrenia. The pattern of findings in this report (larger group differences on backward versus forward masking and on the location condition) suggests that the activity of transient visual channels may be particularly linked to vulnerability.     

Psychopathology and wisconsin card sorting test performance in young unmedicated schizophrenic patients

The relationship between psychopathology and Wisconsin Card Sorting Test (WCST) performance was evaluated in 25 unmedicated young acute schizophrenic female patients (14 neuroleptic-naive and 11 neuroleptic-free) and 15 female controls. The schizophrenic patients (especially the neuroleptic-free) performed more poorly than controls in the WCST. In addition, WCST impairment correlated with both negative and positive symptoms. The results suggest that the neuropsychological dysfunction in schizophrenia is present at the onset of the illness, and is neither secondary to previous neuroleptic treatment nor to chronicity of the illness.     

ECT remission rates in psychotic versus nonpsychotic depressed patients: a report from CORE.

OBJECTIVE: To compare the relative efficacy of electroconvulsive therapy (ECT) in psychotic and nonpsychotic patients with unipolar major depression. METHODS: The outcome of an acute ECT course in 253 patients with nonpsychotic (n = 176) and psychotic (n = 77) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses. ECT was administered with bilateral electrode placement at 50% above the titrated seizure threshold. The remission criteria were rigorous: a score 相似文献