Forty years of structural imaging in psychosis: promises and truth

Fusar‐Poli, Paolo; Meyer‐Lindenberg, Andreas

doi:10.1111/acps.12619

Cited by 45 publications

(31 citation statements)

References 133 publications

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“…For a review on structural MRI measures as predictors of outcome, see Dazzan et al ( 74 ). Outcome prediction based on any of the univariate findings is too inaccurate to be clinically useful ( 75 ). An exception might turn out to be using a lack of elevated dopamine synthesis capacity, which has been associated with antipsychotic treatment resistance in two studies ( 76 , 77 ).…”

Section: Outcome Prediction: Current Evidencementioning

confidence: 99%

Is It Possible to Predict the Future in First-Episode Psychosis?

et al. 2018

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The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features—like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis—are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognostic markers in FEP. Combination of different markers in ML models with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.

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Section: Outcome Prediction: Current Evidencementioning

confidence: 99%

Is It Possible to Predict the Future in First-Episode Psychosis?

et al. 2018

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“…While deficits in working memory have long been proposed as a marker of frontal lobe dysfunction is schizophrenia, an analysis of 30 relevant imaging studies found that half have shown hypofrontality, a few have found no differences, while the remainder noted hyperfrontality [ 28 , 51 ]. A recent meta-analysis of 80 MRI studies of psychoses published between 1976 and 2015 found no diagnostic or prognostic biomarkers [ 52 ]. With regard to depression, a meta-analysis of studies of aberrant brain function during cognitive and emotional processing failed to find any statistically significant evidence of convergence across 59 studies [ 53 ].…”

Section: The Medical Model: Has It Failed Psychiatry?mentioning

confidence: 99%

Social inequality, scientific inequality, and the future of mental illness

Dean

2017

Philos Ethics Humanit Med

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BackgroundDespite five decades of increasingly elegant studies aimed at advancing the pathophysiology and treatment of mental illness, the results have not met expectations. Diagnoses are still based on observation, the clinical history, and an outmoded diagnostic system that stresses the historic goal of disease specificity. Psychotropic drugs are still based on molecular targets developed decades ago, with no increase in efficacy. Numerous biomarkers have been proposed, but none have the requisite degree of sensitivity and specificity, and therefore have no usefulness in the clinic. The obvious lack of progress in psychiatry needs exploration.MethodsThe historical goals of psychiatry are reviewed, including parity with medicine, a focus on diagnostic reliability rather than validity, and an emphasis on reductionism at the expense of socioeconomic issues. Data are used from Thomas Picketty and others to argue that our failure to advance clinical care may rest in part on the rise in social and economic inequality that began in the 1970s, and in part on our inability to move beyond the medical model of specificity of disease and treatment.ResultsIt is demonstrated herein that the historical goal of specificity of disease and treatment has not only impeded the advance of diagnosis and treatment of mental illness, but, in combination with a rapid increase in socioeconomic inequality, has led to poorer outcomes and rising mortality rates in a number of disorders, including schizophrenia, anxiety, and depression.ConclusionsIt is proposed that Psychiatry should recognize the fact of socioeconomic inequality and its effects on mental disorders. The medical model, with its emphasis on diagnostic and treatment specificity, may not be appropriate for investigation of the brain, given its complexity. The rise of scientific inequality, with billions allocated to connectomics and genetics, may shift attention away from the need for improvements in clinical care. Unfortunately, the future prospects of those suffering from mental illness appear dim.

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“…Over recent decades, epidemiological evidence and similarly indirect (“soft”) biological findings indicate that schizophrenia is a disorder of subtle neurodevelopmental abnormality [ 2 , 21 – 23 ]. However, even the most sophisticated of modern structural and functional neuroimaging techniques applied to young adults with psychotic illness, or even to adolescents showing the putative “at risk mental state”/“attenuated psychosis syndrome”, are unable to resolve hallmarks of abnormal brain development [ 24 , 25 ]. The need is for a “hard” index of brain dysmorphogenesis during embryonic and foetal life that can be accessed readily in individuals throughout their lifespan.…”

Section: Schizophrenia: a Neurodevelopmental Disorder With Facial Dysmentioning

confidence: 99%

Translational Genetic Modelling of 3D Craniofacial Dysmorphology: Elaborating the Facial Phenotype of Neurodevelopmental Disorders Through the “Prism” of Schizophrenia

Waddington

Katina

O’Tuathaigh

et al. 2017

Curr Behav Neurosci Rep

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Purpose of ReviewIn the context of human developmental conditions, we review the conceptualisation of schizophrenia as a neurodevelopmental disorder, the status of craniofacial dysmorphology as a clinically accessible index of brain dysmorphogenesis, the ability of genetically modified mouse models of craniofacial dysmorphology to inform on the underlying dysmorphogenic process and how geometric morphometric techniques in mutant mice can extend quantitative analysis.Recent FindingsMutant mice with disruption of neuregulin-1, a gene associated meta-analytically with risk for schizophrenia, constitute proof-of-concept studies of murine facial dysmorphology in a manner analogous to clinical studies in schizophrenia. Geometric morphometric techniques informed on the topography of facial dysmorphology and identified asymmetry therein.SummaryTargeted disruption in mice of genes involved in individual components of developmental processes and analysis of resultant facial dysmorphology using geometric morphometrics can inform on mechanisms of dysmorphogenesis at levels of incisiveness not possible in human subjects.

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Forty years of structural imaging in psychosis: promises and truth

Cited by 45 publications

References 133 publications

Is It Possible to Predict the Future in First-Episode Psychosis?

Is It Possible to Predict the Future in First-Episode Psychosis?

Social inequality, scientific inequality, and the future of mental illness

Translational Genetic Modelling of 3D Craniofacial Dysmorphology: Elaborating the Facial Phenotype of Neurodevelopmental Disorders Through the “Prism” of Schizophrenia

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