Stanley Victor Catts

Psychiatric disorders such as schizophrenia, major depressive disorder, and bipolar disorder have areas of significant overlap across multiple domains including genetics, neurochemistry, symptom profiles, and regional gray matter alterations. Various structural neuroimaging studies have identified a combination of shared and disorder-specific patterns of gray matter (GM) deficits across these different disorders, though few direct comparisons have been conducted. Given the overlap in symptom presentations and GM alterations, these disorders may have a common etiology or neuroanatomical basis that may relate to a certain vulnerability for mental illness. Pooling large data or heterogeneous data can ensure representation of several participant factors, providing more accurate results. However, ensuring large enough datasets at any one site can be cumbersome, costly, and may take many years of data collection. Large scale collaborative research is already facilitated by current data repositories and neuroinformatics consortia such as the Enhacing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium, institutionally supported databases, and data archives. However, these data sharing methodologies can still suffer from significant barriers. Federated approaches can augment these approaches and mitigate some of these barriers by enabling access or more sophisticated, shareable and scaled up analyses of large-scale data which may not be shareable and can easily be scaled up with the number of sites. In the current study, we examined GM alterations using Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC). Briefly, COINSTAC ( https://coinstac.trendscenter.org ) is an open-source decentralized analysis application that provides a venue for analyses of neuroimaging datasets without sharing individual level data, while maintaining granular control of privacy. Through federated analysis, we examined T1-weighted images (N = 3,287) from eight psychiatric diagnostic groups across seven sites. We identified significant overlap in the GM patterns of individuals with schizophrenia, major depressive disorder, and autism spectrum disorder. These results show cortical and subcortical regions, specifically the bilateral insula, that may indicate a possible shared vulnerability to psychiatric disorders.

Murray and colleagues' confident advice[1][1] to psychiatrists, encouraging them to leave fewer patients with schizophrenia on long-term medication, is based on one of several possible interpretations of a selected literature, and little clinical evidence. We consider that at times Murray and

Objective: In response to evidence of deteriorating outcomes of people with schizophrenia we recently published a critical review in the journal concerning why outcomes for schizophrenia are not improving. A published commentary on our review raised criticisms that we aim to address herein. Method: Published data related to four issues raised in the commentary were reviewed. Results: There is a body of evidence that supports the possibility of dramatic improvements in treatment effectiveness, presented in our critical review, and these can be achieved within existing financial resources and present day understanding of the pathophysiology of schizophrenia. However, the commentary leads us to highlight four current obstacles to improving treatment effectiveness: (1) the belief of many psychiatrists that long-term antipsychotic medication raises the cardiovascular mortality rate in schizophrenia when the opposite is almost certainly the case; (2) the need to improve psychiatrist training in diagnostic and communication skills, especially with first episode presentations; (3) the requirement for comprehensive and structured assessment of the highly prevalent deficits in insight and decision making capacity associated with schizophrenia; and (4) the need for improved intervention design to minimise the impact of these deficits on treatment choice and refusal. Conclusion: With a sense of professional urgency, a genuinely respectful and caring partnership between clinicians, affected individuals and their families, and researchers, with relative little innovation, we conclude that the standard of care can definitely be raised now in the treatment of schizophrenia.

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.

People with chronic psychosis often display theory of mind impairments that are not fully accounted for by other, more general neurocognitive deficits. In these patients, both theory of mind and neurocognitive deficits contribute to poor functioning, independently of psychotic symptoms. In young people with recent-onset psychosis, however, it is unclear the extent to which theory of mind impairment is independent of neurocognitive deficits. The primary aim of this study was to examine the evidence for specific theory of mind impairments in early psychosis. A secondary aim was to explore the relations between theory of mind, neurocognition, symptom severity, and functional outcomes. Twenty-three patients who were within two years of their first psychotic episode and 19 healthy controls completed theory of mind and neurocognitive batteries. Social functioning, quality of life, and symptom severity were also assessed in patients. Patients demonstrated deficits in tasks assessing theory of mind and neurocognition relative to controls. Patients’ deficits in theory of mind were evident even after adjusting for their deficits in neurocognition. Neither theory of mind nor neurocognition predicted social functioning or quality of life in this early psychosis sample. Severity of negative symptoms, however, was a significant predictor of both outcomes. While a specific theory of mind impairment was evident in this early psychosis sample, severity of negative symptoms emerged as the best predictor of poor functional outcome. Further early psychosis research is needed to examine the longitudinal progression of theory of mind impairments – independent of neurocognitive deficits – and their impact on psychosocial function.

Objective: The aim of this study was to identify promising elements of best practice relevant to mainstream mental health service (MHS) delivery of early psychosis intervention (EPI) to Indigenous communities. In a companion paper, a comprehensive literature review identified a promising service model with potential for delivering EPI: an Indigenous sub-team embedded within a mainstream health service. Method: This paper describes a consultation process with Indigenous Mental Health Workers (IMHWs) in south eastern Queensland. A case study of the Sunshine Coast Cultural Healing Program (CHP-SC) was carried out during the consultation process. Results: IMHWs agreed that the Australian clinical guidelines for early psychosis were relevant to improving outcomes for Indigenous patients. IMHWs unanimously identified the CHP-SC as a best practice mainstream MHS for delivering EPI. The CHP-SC, which represented an Indigenous sub-team model, was found to be associated with substantially improved engagement of Indigenous young people. Conclusions: We provisionally conclude that specialist EPI could be delivered by specialist Indigenous sub-teams (rather than specialist EPI teams) embedded in mainstream MHSs that incorporate culturally safe practice and are fully integrated with Indigenous primary care services, and recommend that the model be formally evaluated.

Schizophrenia may not be a single disease, but the result of a diverse set of related conditions. Modern neuroscience is beginning to reveal some of the genetic and environmental underpinnings of schizophrenia; however, an approach less well travelled is to examine the medical disorders that produce symptoms resembling schizophrenia. This book is the first major attempt to bring together the diseases that produce what has been termed 'secondary schizophrenia'. International experts from diverse backgrounds ask the questions: does this medical disorder, or drug, or condition cause psychosis? If yes, does it resemble schizophrenia? What mechanisms form the basis of this relationship? What implications does this understanding have for aetiology and treatment? The answers are a feast for clinicians and researchers of psychosis and schizophrenia. They mark the next step in trying to meet the most important challenge to modern neuroscience – understanding and conquering this most mysterious of human diseases.

Aim: Clinical practice improvement carried out in a quality assurance framework relies on routinely collected data using clinical indicators. Herein we describe the development, minimum training requirements, and inter-rater agreement of indicators that were used in an Australian multi-site evaluation of the effectiveness of early psychosis (EP) teams. Methods: Surveys of clinician opinion and face-to-face consensus-building meetings were used to select and conceptually define indicators. Operationalization of definitions was achieved by iterative refinement until clinicians could be quickly trained to code indicators reliably. Calculation of percentage agreement with expert consensus coding was based on ratings of paper-based clinical vignettes embedded in a 2-h clinician training package. Results: Consensually agreed upon conceptual definitions for seven clinical indicators judged most relevant to evaluating EP teams were operationalized for ease-of-training. Brief training enabled typical clinicians to code indicators with acceptable percentage agreement (60% to 86%). For indicators of suicide risk, psychosocial function, and family functioning this level of agreement was only possible with less precise ‘broad range’ expert consensus scores. Estimated kappa values indicated fair to good inter-rater reliability (kappa > 0.65). Inspection of contingency tables (coding category by health service) and modal scores across services suggested consistent, unbiased coding across services. Conclusions: Clinicians are able to agree upon what information is essential to routinely evaluate clinical practice. Simple indicators of this information can be designed and coding rules can be reliably applied to written vignettes after brief training. The real world feasibility of the indicators remains to be tested in field trials.