William T. Carpenter

On the methods and theory of reliability.

This paper reviews the most frequently used and misused reliability measures appearing in the mental health literature. We illustrate the various types of data sets on which reliability is assessed (i.e., two raters, more than two raters, and varying numbers of raters with dichotomous, polychotomous, and quantitative data). Reliability statistics appropriate for each data format are presented, and their pros and cons illustrated. Inadequacies of some methods are highlighted. The meaning of different levels of reliability obtained with various statistics is discussed. This critique is intended for the reading professional and the investigator who has an occasional need of reliability assessment. Statistical expertise is not required and theoretical material is referenced for the interested reader. Necessary formulas for computations are presented in the appendices. A summary table of some suitable reliability measures is presented.

The Psychosis High-Risk State A Comprehensive State-of-the-Art Review

CONTEXT During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. OBJECTIVE To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. DATA SOURCES Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. STUDY SELECTION AND DATA EXTRACTION Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. DATA SYNTHESIS Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. CONCLUSIONS The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses.

Flexible System for the Diagnosis of Schizophrenia: Report from the WHO International Pilot Study of Schizophrenia

Behavioral data on a large patient group were collected by investigators from nine countries in the International Pilot Study of Schizophrenia, sponsored by the World Health Organization. The data on half the group were analyzed to derive a system of 12 signs and symptoms for the identification of schizophrenia, as this disorder is diagnosed in many centers throughout the world. The findings were replicated with the other half of the patient group. The criteria constitute an operational method for identifying patients who would be commonly considered schizophrenic in many centers.

The expert consensus guideline series

Abstract Over the past decade, many new epilepsy treatments have been approved in the United States, promising better quality of life for many with epilepsy. However, clinicians must now choose among a growing number of treatment options and possible combinations. Randomized clinical trials (RCTs) form the basis for evidence-based decision making about best treatment options, but they rarely compare active therapies, making decisions difficult. When medical literature is lacking, expert opinion is helpful, but may contain potential biases. The expert consensus method is a new approach for statistically analyzing pooled opinion to minimize biases inherent in other systems of summarizing expert opinion. We used this method to analyze expert opinion on treatment of three epilepsy syndromes (idiopathic generalized epilepsy, symptomatic localization-related epilepsy, and symptomatic generalized epilepsy) and status epilepticus. For all three syndromes, the experts recommended the same general treatment strategy. As a first step, they recommend monotherapy. If this fails, a second monotherapy should be tried. Following this, the experts are split between additional trials of monotherapy and a combination of two therapies. If this fails, most agree the next step should be additional trials of two therapies, with less agreement as to the next best step after this. One exception to these recommendations is that the experts recommend an evaluation for epilepsy surgery after the third failed step for symptomatic localization-related epilepsies. The results of the expert survey were used to develop user-friendly treatment guidelines concerning overall treatment strategies and choice of specific medications for different syndromes and for status epilepticus.

The prediction of outcome in schizophrenia. IV: Eleven-year follow-up of the Washington IPSS cohort.

Two and five-year follow-up observations of the International Pilot Study of Schizophrenias Washington cohort provided data bearing on several controversial issues regarding the course of schizophrenia. Forty schizophrenic patients have now been observed 11 years after their index admission. Social, occupational, hospital utilization, and symptom areas of functioning continue to be only modestly correlated with one another and do not become increasingly uniform over time. Initial prognostic variables continue to be more predictive of long-term outcome than are cross-sectional symptom manifestations. Restricted affect at the initial evaluation had been a predictor of 5-year outcome, but it was not a significant predictor of outcome at 11 years. While serious long-term consequences of illness are observed, the follow-up data suggest that the illness tends to reach a plateau of psychopathology early in the course, with as many patients tending to improve in the long-term as those who tend to show further deterioration.

Domains of psychopathology: an approach to the reduction of heterogeneity in schizophrenia.

The manifest clinical heterogeneity of schizophrenia, combined with the failure, to date, to demonstrate the existence of a unitary disease process, has led to the conceptualization of schizophrenia as a pathophysiologically heterogeneous disorder. Various approaches have been developed to define homogeneous subgroups of schizophrenic patients. An alternative approach to the use of multiple criteria for defining putative disease entities is the use of specific sign and symptom complexes, or domains of psychopathology, for reducing heterogeneity. There is now considerable evidence supporting the separation of schizophrenic symptoms into three domains: hallucinations and delusions, thought disorder, and deficit symptoms. The conceptual evolution and validating evidence for this approach are reviewed, and an illustration of how the domains of psychopathology are applied in schizophrenia research is presented.

Exploring the feasibility of a meta­structure for DSM­V and ICD­11: could it improve utility and validity?

BACKGROUND The organization of mental disorders into 16 DSM-IV and 10 ICD-10 chapters is complex and based on clinical presentation. We explored the feasibility of a more parsimonious meta-structure based on both risk factors and clinical factors. METHOD Most DSM-IV disorders were allocated to one of five clusters as a starting premise. Teams of experts then reviewed the literature to determine within-cluster similarities on 11 predetermined validating criteria. Disorders were included and excluded as determined by the available data. These data are intended to inform the grouping of disorders in the DSM-V and ICD-11 processes. RESULTS The final clusters were neurocognitive (identified principally by neural substrate abnormalities), neurodevelopmental (identified principally by early and continuing cognitive deficits), psychosis (identified principally by clinical features and biomarkers for information processing deficits), emotional (identified principally by the temperamental antecedent of negative emotionality), and externalizing (identified principally by the temperamental antecedent of disinhibition). CONCLUSIONS Large groups of disorders were found to share risk factors and also clinical picture. There could be advantages for clinical practice, public administration and research from the adoption of such an organizing principle.

Advances in schizophrenia

Recent studies into the etiology of schizophrenia have yielded both promising leads and disappointing dead ends, indicating the multifactored and complex nature of the disorder. The focus has subsequently shifted back to refining the phenotype and identifying clinical and biological subtypes. Recent technological breakthroughs in genomics and proteomics hold promise for advancing our understanding of the molecular pathophysiology of schizophrenia.

Positron emission tomography in schizophrenic patients with and without neuroleptic medication

Positron emission tomography using [18F]2-fluoro-2-deoxy-d-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradients.

Deconstructing negative symptoms of schizophrenia: Avolition–apathy and diminished expression clusters predict clinical presentation and functional outcome

BACKGROUND Previous studies indicate that negative symptoms reflect a separable domain of pathology from other symptoms of schizophrenia. However, it is currently unclear whether negative symptoms themselves are multi-faceted, and whether sub-groups of patients who display unique negative symptom profiles can be identified. METHODS A data-driven approach was used to examine the heterogeneity of negative symptom presentations in two samples: Study 1 included 199 individuals with schizophrenia assessed with a standard measure of negative symptoms and Study 2 included 169 individuals meeting criteria for deficit schizophrenia (i.e., primary and enduring negative symptoms) assessed with a specialized measure of deficit symptoms. Cluster analysis was used to determine whether different groups of patients with distinct negative symptoms profiles could be identified. RESULTS Across both studies, we found evidence for two distinctive negative symptom sub-groups: one group with predominantly Avolition-Apathy (AA) symptoms and another with a predominantly Diminished Expression (DE) profile. Follow-up discriminant function analyses confirmed the validity of these groups. AA and DE negative symptom sub-groups significantly differed on clinically relevant external validators, including measures of functional outcome, premorbid adjustment, clinical course, disorganized symptoms, social cognition, sex, and ethnicity. CONCLUSIONS These results suggest that distinct subgroups of patients with elevated AA or DE can be identified within the broader diagnosis of schizophrenia and that these subgroups show clinically meaningful differences in presentation. Additionally, AA tends to be associated with poorer outcomes than DE, suggesting that it may be a more severe aspect of psychopathology.