Prominent Positive Symptoms Research Articles

Randomized Controlled Trial of Clozapine and CBT for First-Episode Psychosis with Enduring Positive Symptoms: A Pilot Study.

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria (n = 48) were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time.

Impaired decision making in schizophrenia and orbitofrontal cortex lesion patients

Background The aim of this study was to examine impaired decision making in patients with schizophrenia and in patients with orbitofrontal cortex lesions. Methods Schizophrenia patients ( N = 21), healthy controls ( N = 20) and an independent group of orbitofrontal patients ( N = 10) underwent a computerized version of the “Regret Gambling Task”. Participants chose between two gambles, each having different probabilities and different expected monetary outcomes, and rated their emotional states after seeing the obtained outcome. Regret was induced by providing information about the outcome of the unchosen gamble. Results Healthy controls reported emotional responses consistent with counterfactual reasoning between obtained and unobtained outcomes; they chose minimizing future regret and were able to learn from their emotional experience. In contrast, orbitofrontal patients and schizophrenia patients with prominent positive symptoms did not report any regret and did not anticipate any negative consequences of their choices. Our results demonstrate first the presence of very different behavioural deficits within the spectrum of schizophrenia patients which may have contributed to the discrepancies observed in previous studies. Second, the results suggest that a subgroup of schizophrenia patients might have an orbitofrontal dysfunction, in fact, schizophrenia patients with positive symptoms have a behavioural dysfunction analogous to that of the orbitofrontal patients. Conclusion Schizophrenia patients with prominent positive symptoms were unable to integrate cognitive and emotional components of decision making which may contribute to their inability to generate adaptive behaviours in social and individual environments.

Prosodic discrimination in patients with schizophrenia

Fifteen patients with prominent positive symptoms of schizophrenia and 15 normal controls performed verbal prosodic and pure musical discrimination tasks, with changes in pitch and timing parameters. The patients' performance was comparable to that of controls on the discrimination of terminal pitch changes, but significantly poorer on the more difficult internal pitch discrimination. The latter deficit was positively correlated with the severity of their positive symptoms. The results suggest that patients have a deficit in processing fundamental aspects of prosody, which is associated with the presence of positive symptoms.

Inhibition of Return in the Human 5HT2A Agonist and NMDA Antagonist Model of Psychosis

Patients with schizophrenia exhibit disturbances of orienting of attention. However, findings have been inconsistent. Pharmacologic challenges with hallucinogens have been used as models for psychosis. The NMDA antagonist state (PCP, ketamine) resembles undifferentiated psychoses with positive and negative symptoms, while the 5-HT(2A) agonist state (LSD, dimethyltryptamine (DMT)) is thought to be an appropriate model for psychoses with prominent positive symptoms. The aim of this study was to investigate orienting of attention in the human NMDA antagonist and 5-HT(2A) agonist models of psychosis. A total of 15 healthy volunteers participated in a randomized, double-blind, crossover study with a low and a high dose of DMT and S-ketamine, which elicited subtle 'prepsychotic' or full-blown psychotic symptoms (low and high dose, respectively). Nine subjects completed both experimental days with the two doses of both drugs. Overall, both hallucinogens slowed down reaction times dose dependently (DMT >S-ketamine) and DMT diminished the general response facilitating (alerting) effect of spatially neutral cues. Inhibition of Return (IOR), that is, the normal reaction time disadvantage for validly cued trials with exogenous cues and long cue target intervals, was blunted after both doses of DMT and the low dose of S-ketamine. IOR reflects an automatic, inhibitory mechanism of attention, which is thought to protect the organism from redundant, distracting sensory information. In conclusion, our data suggest a deficit of IOR in both hallucinogen models of psychosis, with the effect being clearer in the serotonin model. Blunted IOR may underlie or predispose to different psychotic manifestations, but particularly to those with prominent positive symptoms.

Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia: a multivariate analysis of a large naturalistic study in the hospital setting

This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness. This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients' entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed. Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007). Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.

Modulation of Striatal Dopamine Release by Glycine Transport Inhibitors

Traditional models of schizophrenia have focused primarily upon dopaminergic (DA) dysregulation. In contrast, more recent models focus on dysfunction of glutamatergic systems, acting particularly through N-methyl-D-aspartate (NMDA) receptors. NMDA receptors in brain are regulated by glycine, acting via a strychnine-insensitive regulatory site, and by glycine (GlyT1) transporters that maintain low glycine levels in the immediate vicinity of the NMDA receptor complex. The present study investigates the role of NMDA receptors in the modulation of striatal dopamine release in vitro, and of glycine transport inhibitors (GTIs) as potential psychotherapeutic agents in schizophrenia. In striatum, NMDA receptors exert dual excitatory/inhibitory effects, with inhibition reflecting activity of local GABAergic feedback regulation. We have previously demonstrated effectiveness of glycine in regulating [3H]DA release both in vivo and in vitro, consistent with its beneficial clinical effects. In the present study, similar effects were observed for the high-affinity GTI (+)N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy-)propyl]sarcosine (NFPS), and for a range of high-affinity GTIs with appropriate rank order of potency. In addition, (+)NFPS significantly stimulated NMDA-induced [3H]GABA release. Effects, of GTIs, were blocked by the glycine-site antagonists L689,560 and HA-966, and the GABA(B) antagonists phaclofen and CGP 52432, confirming the roles of both the NMDA-associated glycine-site and presynaptic GABA(B) receptors in NMDA receptor-mediated regulation of striatal DA release in vitro. Endogenous DA hyperactivity is associated with prominent positive symptoms in schizophrenia. The present results are consistent with recent clinical studies showing significant effectiveness of glycine-site agonists and GTIs in reduction of persistent positive, as well as negative, symptoms in schizophrenia.

Cannabis and schizophrenia: impact on onset, course, psychopathology and outcomes.

Cannabis consuming schizophrenic patients are younger at onset, are likely to have started abuse before onset of schizophrenia and show more prominent positive symptoms than nonabusers. It has been suggested that cannabis is a risk-factor for schizophrenia. Our aim was to assess prevalence and pattern of cannabis use in 125 chronic male schizophrenic subjects and its impact on socioepidemiological and clinical variables as well as which disorder precedes the other in onset. Assessment of consumption was made with a semi-structured clinical interview. Clinical status was assessed by means of the SANS, SAPS, PANSS and BPRS scales. Cannabis consumption was found in 54 subjects (43%), 66.7% of whom started it at least three years before onset of schizophrenia. Consumers were younger and with lower negative symptoms, specially abusers and polysubstance abusers. Family history positive for psychosis was more frequent in consumers, especially when consumption started before onset of schizophrenia. Subjects whose onset of schizophrenia preceded the beginning of cannabis abuse had more positive symptoms than those who started abuse before the onset of schizophrenia. On these grounds, our sample could be subdivided into two main groups, one that uses substances to counter distressing symptoms of schizophrenia and another in which cannabis might be one of the factors predisposing to the disease; the former had less negative symptoms than nonabusers. Our data support both heterogeneity of schizophrenia and genetic susceptibility to environmental agents.

Obstetric complications and Apgar score in early-onset schizophrenic patients with prominent positive and prominent negative symptoms

The objective of the study was to find associations between obstetric complications (OCs) history and schizophrenia course and symptoms. We analysed the obstetric and psychiatric history of 50 DSM IV schizophrenic subjects who experienced their first schizophrenia episode in adolescence, and 30 healthy controls. Obstetrical data and Apgar scores were obtained from medical records and evaluated with the Lewis and Murray Scale. Based on patients’ documentation [including longitudinal evaluation with Positive and Negative Syndrome Scale (PANSS)] the symptom profile and the course of schizophrenia were determined. Results: we distinguished two major groups of patients: with prominent negative and prominent positive symptoms. Schizophrenics with prominent negative symptoms and a chronic schizophrenia course had significantly more definite OCs and lower Apgar scores than patients with prominent positive symptoms and controls. Subjects who had a positive OCs history were more than four times likely to develop schizophrenia in adolescence than those without such a history (OR=4.64; 95% CI=1.29–17.51) with the likelihood of developing schizophrenia with prominent negative symptoms especially high (OR=7.31; 95% CI=1.80–29.65). An Apgar score of between 0 and 3 after birth was associated with an increased risk for developing schizophrenia (OR=2.25; 95% CI=0.56–9.12), especially with prominent negative symptoms (OR=3.71; 95% CI=0.84–16.32). The findings support the hypothesis of a role of OCs in developing early-onset schizophrenia and suggest the associations of the OCs history with a specific symptoms profile (prominent negative symptoms) and a chronic course of schizophrenia.

Violence in psychiatric patients: The role of psychosis, frontal lobe impairment, and ward turmoil

The purpose of the study was to identify psychiatric symptoms, neurological impairments, and situational factors associated with the emergence of violence and with its persistence. Psychiatric symptoms were assessed in newly admitted physically assaultive psychiatric patients and nonviolent controls. Patients were then evaluated for 4 weeks to determine the persistence or resolution of these physical assaults. Patients who showed marked resolution of assaults were classified as transiently violent (n = 41), and those who remained assaultive throughout were categorized as persistently violent (n = 34). At the end of 4 weeks, all patients received a comprehensive psychiatric and neurological assessment. Physical assaults were associated initially with prominent positive psychotic symptoms. Both transiently and persistently violent patients were more psychotic than the nonviolent controls; however, transiently violent patients showed better resolution of these symptoms over the 4 weeks. They also evidenced less frontal lobe impairment on the neurological examination than the persistently violent patients. The two violent groups differed in their susceptibility to environmental influences: the surrounding ward agitation fostered physical assaults in transiently but not in persistently violent patients. This differentiation between transiently and persistently violent patients has major implications for the comprehensive treatment of violent behavior.

Cannabis and schizophrenia: a longitudinal study of cases treated in Stockholm County.

By means of the Stockholm County inpatient care register we identified all cases treated with a diagnosis of cannabis dependence and psychosis, not necessarily at the same occasion, during 1971-1983. By scrutinizing medical records, we evaluated the diagnosis according to DSM-III-R and we assessed the history of substance abuse as well as the psychiatric history and clinical course. We identified 229 cases during the follow-up; 112 of these cases (49%) fulfilled the DSM-III-R criteria for schizophrenia. The majority of the schizophrenics had prominent positive symptoms and a sudden onset of disease, and 69% of the cases had a record of heavy cannabis abuse at least 1 year before onset of psychotic symptoms. The high number of verified DSM-III-R cases of schizophrenia in this cohort and the temporal relation between cannabis abuse and schizophrenia further support the hypothesis that cannabis abuse may be a risk factor for schizophrenia. We confirmed previous observations that cannabis-associated schizophrenia often has a sudden onset and prominent positive symptoms.

The Nithsdale schizophrenia survey: I. Psychiatric and social handicaps.

A review of all known schizophrenics from a discrete geographical area, Nithsdale in Dumfries and Galloway REgion, found a point prevalence of 2.38 per 1000 of the total population; this figure fell to 1.73 when only Feighner positive schizophrenics were considered. Only 3 per cent of the population interviewed had no abnormality in mental state or behaviour; negative schizophrenic symptoms were prominent, positive symptoms uncommon. Approximately one quarter were in-patients, who were an atypical group, showing much more obvious social and psychiatric disability. In- and day patient care and state benefits for schizophrenics cost each member of the Nithsdale community approximately 12 pounds a year.