Apoptosis and schizophrenia: a pilot study based on dermal fibroblast cell lines

Introduction: The aim of this study was to investigate whether there is an increased susceptibility to apoptosis in cultured fibroblasts from patients with schizophrenia

The treatment of schizophrenia: can we raise the standard of care?

Objective: There is evidence that over time health outcomes of people with schizophrenia are deteriorating rather than improving both in terms of mortality rate and levels of morbidity, even in Australia where service resourcing is substantial. Our objective was to examine the evidence of whether poor outcomes reflect decreases in treatment effectiveness and, if so, what are the barriers to improving standards of care. This review will argue that the confidence of clinicians to diagnose schizophrenia early, and provide assertive and long-term care, may be being undermined by a series of controversies in the published literature and discrepancies in clinical practice guidelines. Method: A critical review was conducted of the evidence regarding six issues of high clinical relevance to the treatment of schizophrenia formulated as questions: (1) Is schizophrenia a progressive disease? (2) Does relapse contribute to disease progression and treatment resistance? (3) When should the diagnosis of schizophrenia be made? (4) Should maintenance antipsychotic medication be discontinued in fully remitted first-episode patients? (5) Do antipsychotic medications cause deleterious reductions in cortical grey matter volumes? and (6) Are long-acting injectable antipsychotics more effective in reducing relapse rate compared to oral formulations? Results: There is reliable evidence for schizophrenia being a progressive disease with emergent treatment resistance in most cases, that relapse contributes to this treatment resistance, that maintenance antipsychotic medication should not be discontinued in remitted first-episode patients, that antipsychotic medication does not appear to cause deleterious grey matter volume changes, that maintenance antipsychotic medication reduces the mortality rate in schizophrenia and that long-acting injectable antipsychotics are more effective in preventing relapse than oral formulations. Conclusion: There is an urgent need to re-engineer the early management of schizophrenia and to routinely evaluate this type of innovation within practice-based research networks. A proposal for an assertive treatment algorithm is included

Evidence of aberrant DNA damage response signalling but normal rates of DNA repair in dividing lymphoblasts from patients with schizophrenia

Objectives. Cancer incidence in schizophrenia is not increased commensurate with higher rates of risk exposures. Here we report an investigation of the DNA damage response, an anti-tumorigenic defence, in immortalised lymphoblasts from patients with schizophrenia. Methods. Unirradiated and irradiated (5Gy) lymphoblasts from schizophrenia patients (n = 28) and healthy controls (n = 28) were immunostained for the phosphorylated histone variant H2AX (gamma H2AX), an index of DNA double-strand breaks. Flow cytometry was used to assess cell cycle distribution and gamma H2AX immunofluorescence. Rate of DNA repair was quantified by determining the temporal change in gamma H2AX values following irradiation. Results. In unirradiated lymphoblasts, gamma H2AX levels were significantly increased in the schizophrenia group compared with controls (effect size = 0.86). This increase was most evident in patients with cognitive deficits. In irradiated lymphoblasts, peak radiation-induced gamma H2AX levels were significantly reduced in patients. No differences between patients and controls were found in the rate of DNA repair or in cell cycle distribution. Conclusions. The significant differences in DNA damage response signalling observed involve modification of histone variant H2AX and thereby implicate regulatory processes determining chromatin structure in dividing lymphoblasts from patients with schizophrenia. The role that aberrant DNA damage response signalling plays in protecting patients from cancer is unclear

Real-world use of quetiapine in early psychosis: An acute inpatient and community follow-up effectiveness study

Objective. To evaluate the use of quetiapine in first episode psychosis in adolescents and adults in a 26-week open-label trial. Methods. Consenting patients were recruited from consecutive acute psychiatric admissions. Quetiapine was increased stepwise to 750 mg. Baseline, 2, 4, 12, 16, 20 and 26 week measurement included: BPRS, PANSS, CGI, and indices of tolerability and safety. Change was assessed using repeated measures ANOVA. Results. Of 73 first admission patients with psychosis, 15 entered the study. Loss of otherwise eligible patients was mainly related to prospective consent, which appeared to cause selection bias. All 15 patients were retained for 4-week Intention-to-Treat Analysis; nine completed the 26-week protocol (Completers Analysis). Non-completers dropped out shortly after 4 weeks. In the ITT Analysis, there was significant improvement on BPRS Total (P < 0.01), PANSS Positive (P < 0.05), and CGI (P < 0.01) scores. No change in the 2-week BPRS Total score predicted subsequent non-response to quetiapine. In the Completers Analysis, onset of significant PANSS Negative score reduction did not occur until week 12. By 26 weeks all efficacy measures had substantially improved; and substance abuse was markedly less prevalent (P=0.02). Adverse events included postural hypotension, drowsiness, and significant weight gain (P = 0.001). Conclusions. This uncontrolled trial suggests quetiapine is an effective first-line treatment in young early psychosis patients. Prospective consent is a major barrier to evaluating acute care for psychotic disorder