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Objective: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines., Method: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus., Results: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients., Conclusions: There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.

Rationale: Cognitive impairment associated with schizophrenia is a key predictor of functional outcomes. The FDA-accepted MATRICS Consensus Cognitive Battery (MCCB) is held to be the gold standard measure but there are concerns about its ease of administration, reliance on language causing problems with translation and possible practice effects. The CogState Schizophrenia Battery (SB) is suggested as a non-language-based alternative but there is no substantial, independent comparison., Objectives: The objective of this study was to assess the reliability and validity of these two assessment batteries., Methods: One hundred forty-three participants with DSM-IV schizophrenia and schizoaffective disorder were recruited into three similar studies. Each study administered MCCB and SB tests on consecutive days (baseline 1 and 2) and follow-up 3-4 weeks later., Results: Batteries' test-retest reliability was similar: SB composites correlated r = 0.66-0.78 between baselines, MCCB domains r = 0.69-0.90. Baseline 2 and follow-up SB composites correlated r = 0.65-0.80 and MCCB domains r = 0.62-0.87. MCCB tasks' practice effects (Glass' ∆ = 0.02-0.46) exceeded SB's (Glass' ∆ = 0.02-0.34). While the batteries' total scores correlated strongly (r = 0.79-0.82), apparently equivalent cognitive domains on each battery (e.g. psychomotor-attention) correlated r = 0.22-0.60, indicating substantial differences between some supposed counterparts., Conclusions: Clinical trials using either battery would benefit from initial practice sessions to ameliorate practice effects but the SB may be more suitable to measure change in the absence of repeated baselines. The MCCB domains' better correlations with social skills performance suggest that it may have an advantage for measuring cognition in relation to functional outcome.

Neurocognitive impairment predicts disability in schizophrenia, making intervention theoretically attractive as a means to minimise chronic disability. Many trials confirm that cognitive remediation (CR) produces meaningful, durable improvements in cognition and functioning but fewer focus on the early stages. We systematically reviewed CR trials in early schizophrenia to determine its efficacy on global cognition, functioning and symptoms. Two reviewers independently searched electronic databases to identify randomised controlled trials investigating CR following a first episode of psychosis. Eleven trials with 615 participants were identified. Random effect models revealed a non-significant effect of CR on global cognition (effect size=0.13, 95% CI -0.04, 0.31; p0.14), p<0.05 in sensitivity analysis (effect size 0.19; CI 0.00, 0.38). One of seven neurocognitive domains showed a significant positive effect (verbal learning and memory) and five others showed borderline significant benefits. There was a significant effect on functioning (0.18; CI 0.01, 0.36; p<0.05) and symptoms (0.19; CI 0.02, 0.36; p<0.05). CR's effect on functioning and symptoms was larger in trials with adjunctive psychiatric rehabilitation and small group interventions. CR's effect sizes in early illness were smaller than those in chronic schizophrenia, perhaps because of participants' reduced scope for improvement, though trials' small number and size produces uncertain estimates of effect. However, significant benefits were seen in functioning and symptoms and moderator analyses indicate factors that may increase CR's effect. Findings here, theoretical considerations and trials in chronic schizophrenia suggest that targeting social cognition might also enhance its efficacy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Quality of life (QoL) is considered an important outcome in health research. It can be rated by the patient, or by an external assessor. We wished to identify the predictors of any discrepancies between these two approaches in people with schizophrenia., Methods: Patients with DSM schizophrenia and related disorders (N = 80) completed both patient-rated (Lancashire Quality of Life Profile; LQOLP) and assessor-rated (Heinrich's Quality of Life Scale; QLS) measures of QoL., Results: Patient-rated (LQOLP) and assessor-rated (QLS) measures showed a modest correlation (r = 0.38). In a regression analysis, independent predictors of subjectively-rated QoL being higher than objectively-assessed QoL in the same patient, were low insight score (BIS), negative symptoms (PANSS), absence of depression (CDSS), and less positive attitude toward prescribed treatment (DAI)., Conclusions: In people with schizophrenia, scores on objectively- and subjectively-rated measures of quality of life can differ markedly. When comparing subjective to objective assessments, patients with depressive symptoms will value their QoL lower, and those with low insight will value their QoL higher. This has important implications for the utility and interpretation of QoL measures in schizophrenia.

Objectives: The aim of the study was to investigate sexual function in patients with schizophrenia receiving treatment with a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) drug. Sexual function is an important aspect of human experience, which can be affected by antipsychotic drug treatment. Sexual dysfunction in patients with schizophrenia may be less prevalent with SGA than with FGA drug treatment., Methods: A cross-sectional prevalence study assessed sexual function in a sample of 144 patients with DSM-IV schizophrenia aged between 18 and 65, using the Derogatis Interview for Sexual Functioning (self-report version: DISF-SR). Two equal-sized groups (N = 72) received treatment with an FGA or an SGA drug for at least 12 weeks., Results: No significant differences were seen on DISF-SR total score or subscale score between the two treatment groups., Conclusions: There are no differences in measured sexual function of non-randomised patients with schizophrenia treated with an FGA compared with SGA-treated patients.

Introduction: We predicted that participants with schizophrenia would be able to successfully "align" during conversation in the context of impaired theory of mind. Alignment is a process by which interlocutors' representations of the conversational situation converge; and it may, in part, explain how people with schizophrenia can often participate successfully in dialogue despite experiencing impaired mentalising., Methods: Fifty-nine people with schizophrenia and 38 healthy adults completed a standardised, empirical conversational alignment task with a mentalising component and a measure of current IQ. The patients also completed two independent theory of mind tests. We used ANCOVAs to compare the groups' performances., Results: The participants with schizophrenia and the healthy participants demonstrated equivalent alignment skills even though the schizophrenia participants displayed clear theory of mind difficulties. Symptom subtype analyses found no differences between subtype groups in alignment, but healthy controls and remitted patients performed significantly better on the mentalising component than the paranoia group., Conclusions: These results are consistent with the schizophrenia participants having intact alignment skills alongside mentalising impairments. We propose that this explains why people with schizophrenia can often participate successfully in conversation but have difficulties with more complex dialogues, with resolving misunderstandings, and with untangling ambiguities during conversation.

Objective: To estimate the effect of insight on time to relapse and readmission and on social function and symptoms after following up a cohort of first-episodes of nonaffective psychosis for 18 months., Method: Patients with first episodes of DSM-IV schizophreniform disorder, schizophrenia, schizoaffective disorder, delusional disorder, and psychosis not otherwise specified (excluding primary substance-induced or organic psychoses), aged 16 to 65 years, were recruited over the 26 months from July 1996 to September 1998 from consecutive admissions to day-patient and inpatient units in England with a catchment area population of 2.3 million. They were interviewed with the Positive and Negative Syndrome Scale, Birchwood Insight Scale, and Social Functioning Scale at baseline and 18 months., Results: The hazard ratio for relapse, per unit increase in the insight score, was estimated in a Cox proportional hazards model to be 0.943 (95% CI = 0.892 to 0.996; p = .035). Those with the best insight scores had an estimated rate of relapse that was 39% of that of those with the worst scores (95% CI = 16% to 93%). Readmission was highly correlated with relapse, so poor insight also predicted readmission (hazard ratio 0.934; 95% CI = 0.876 to 0.996; p = .036). However, insight did not independently predict symptoms or social function after adjustment for other predictors of outcome., Conclusion: Insight predicted both relapse and readmission. The details of the beliefs and assumptions determining outcome remain unclear, but intervening to alter them appears to be justified.