The Concept of Staging in Schizophrenia; 13 Years After the 'Agius Concept of Staging' Was Published.

We review the development of clinical staging models of schizophrenia, which has developed as a logical extension of the Neuro-developmental theory of Schizophrenia. The staging approach, which involves assessing a disorder based on its severity, scope, progression, and characteristics, is gaining growing recognition in the fields of clinical psychology and psychiatry. We review the development of clinical staging models of schizophrenia, which has developed as a logical extension of the Neuro-developmental theory of Schizophrenia. The development of these clinical staging models should be based also on the neuroimaging dana, since this implies actual changes within the brain. There still are some difficulties with these models, but they are gradually providing both more logical ways of understanding the development of psychotic illness and more effective ways of treatment. The Models have contributed to research in several areas of psychiatry.

White matter alterations and the conversion to psychosis: A combined diffusion tensor imaging and glutamate 1H MRS study.

INTRODUCTION: Widespread white matter abnormalities and alterations in glutamate levels have been reported in patients with schizophrenia. We hypothesized that alterations in white matter integrity and glutamate levels in individuals at clinical high risk (CHR) for psychosis are associated with the subsequent development of psychosis. METHODS: Participants included 33 antipsychotic naïve CHR (Female 7/Male 26, Age 19.55 (4.14) years) and 38 healthy controls (Female 10/Male 28, Age 20.92 (3.37) years). Whole brain diffusion tensor imaging for fractional anisotropy (FA) and right frontal white matter proton magnetic resonance spectroscopy for glutamate levels were acquired. CHR participants were clinically followed for 2 years to determine conversion to psychosis. RESULTS: CHR participants that transitioned to psychosis (N = 7, 21%) were characterized by significantly lower FA values in the posterior thalamic radiation compared to those who did not transition and healthy controls. In the CHR group that transitioned to psychosis only, positive exploratory correlations between glutamate levels and FA values of the posterior thalamic radiation and the retrolenticular part of the internal capsule and a negative correlation between glutamate levels and the cingulum FA values were found. CONCLUSION: The results of the present study highlight that alterations in white matter structure and glutamate are related with the conversion to psychosis.

Negative Symptom Domains in Children and Adolescents at Ultra-High Risk for Psychosis: Association With Real-Life Functioning.

Background: Negative symptoms (NS) appear early in subjects at ultra-high risk (UHR) for psychosis and may increase the risk of conversion to psychotic disorders and poor outcome. Contrary to schizophrenia, there is no consensus on the conceptualization and factor structure of NS in UHR subjects. This study aims to explore NS prevalence, factor structure, and impact on the outcome of UHR state in children and adolescents. Methods: 71 UHR were recruited at the Neuropsychiatry Unit of the Hospital Bambino Gesù in Rome. We examined the prevalence of NS of at least moderate severity, the factor structure of NS by Principal Component Analysis (PCA) and Confirmatory Factor Analysis (CFA), and correlations between extracted factors and functioning. We also evaluated the severity of baseline NS in subjects who converted to psychosis (converters) and in those who did not convert (nonconverters) at 1-year follow-up. Results: At baseline, all participants showed at least one NS of at least moderate severity. PCA and CFA yielded a two-factor solution: an ''Expressive" and an "Experiential" factor. Only the Experiential factor was associated with functioning. At baseline, severity of NS did not differ between converters (N = 16) and nonconverters (N = 55). Conclusions: In UHR children and adolescents NS have a high prevalence, a significant impact on functioning, and cluster in two-factors. Replications by independent studies, with state-of-the-art instruments and longer duration of follow-up, are needed to improve the characterization of NS in this population, clarify their impact on the outcome and enhance their early identification, prevention, and treatment.

An imaging-based risk calculator for prediction of conversion to psychosis in clinical high-risk individuals using glutamate 1H MRS.

Risk calculators for prediction of conversion of Clinical High-Risk (CHR) individuals to syndromal psychosis have recently been developed and have generated considerable clinical use and research interest. Predictor variables in these calculators have been clinical rather than biological, and our goal was to incorporate a neurochemical imaging measure into this framework and assess its impact on prediction. We combined striatal glutamate 1H MRS data with the SIPS symptoms identified by the Columbia Risk Calculator as having the greatest predictive value in order to develop an imaging-based risk calculator for conversion to psychosis. We evaluated the calculator in 19 CHR individuals, 7 (36.84%) of whom converted to syndromal psychosis during the 2-year follow up. The receiver operating characteristic (ROC) curve for the logistic model including only striatal glutamate and visual perceptual abnormalities showed an AUC = 0.869 (95% CI = [0.667, 1.000]) and AUCoa = 0.823, with sensitivity of 0.714, specificity of 0.917, positive predictive value of 0.833, and negative predictive value of 0.846. These results represent modest improvements over each of the individual ROC curves based on either striatal glutamate or visual perceptual abnormalities alone. The preliminary model building and evaluation presented here in a small CHR sample suggests that the approach of incorporating predictive imaging measures into risk classification is not only feasible but offers the potential of enhancing risk assessment.

Inflammatory biomarkers in individuals at clinical high risk for psychosis (CHR-P): State or trait?

BACKGROUND: Studies linking neuro-inflammation to psychotic episodes has been rapidly expanding. Assessments of changes in inflammatory biomarkers in prodromal patients who subsequently convert to psychosis may help in predicting those likely to transition to psychosis. METHODS: We reviewed the literature for original studies that measured inflammatory biomarkers in individuals at clinical high risk for psychosis (CHR-P), and compared pro-inflammatory biomarker data between converters and non-converters to psychosis as well as in healthy controls. RESULTS: Our search yielded 15 studies. Our findings suggest a possible role of plasma levels of Interleukins-1ß, 7, 8, matrix metalloproteinase (MMP)-8, cortisol, albumin and salivary cortisol, measured at baseline, as predictors of psychotic transition. Both baseline C-reactive protein (CRP) and Interleukin-6 levels were not shown to discriminate between converters and non-converters to psychosis. The dearth of longitudinal biomarker measures, before and after treating the psychotic episodes, was a limitation for assessing inflammatory biomarkers as trait vs state marker properties of biomarkers. DISCUSSION: Gaps of data in published studies prevent confirming whether inflammatory biomarkers are state or trait indicators of transition to psychosis in the CHR-P populations. Future investigations should be designed to longitudinally measure inflammatory biomarkers in order to navigate the extensive heterogeneity of the schizophrenia syndrome and its prodrome.

Attenuated first-rank symptoms and conversion to psychosis in a clinical high-risk cohort.

AIM: We sought to examine attenuated first-rank symptoms (FRS) and subcomponents of the Unusual Thought Content (P.1.) section of the Structured Interview for Psychosis-Risk Syndromes (SIPS) to investigate the robust relationship between total P.1. and conversion. We hypothesized that attenuated FRS would drive the association and, additionally, be most predictive of a schizophrenia diagnosis. METHOD: We assessed 189 clinical high-risk participants. Two independent raters separately scored attenuated FRS and each subcomponent of P.1. as if each were the only symptom reported. Total P.1. was also scored. Participants were evaluated for conversion up to 2 years. RESULTS: While total P.1. score significantly predicted conversion in the 54 converters, attenuated FRS, which were relatively uncommon in this sample, nor any subcomponent of P.1., was independently predictive. FRS did not predict conversion to schizophrenia among 35 subjects. CONCLUSION: Although attenuated FRS, and subcomponents of P.1. of the SIPS, did not significantly predict transition to psychosis, our results support previous research affirming the value of total P.1. score as a tool for predicting conversion to psychosis.