Schizophrenia Bulletin

Published by Oxford University Press (OUP)
Online ISSN: 0586-7614
Publications
Article
Objective: To carry out an up-to-date comprehensive survey of the content and quality of intervention trials relevant to the treatment of people with schizophrenia. Design: Data were extracted and analyzed from 10,000 trials on the Cochrane Schizophrenia Group's Register. Main outcome measures: Source, type and date of publication, country of origin, language, size of trial, interventions, and outcome measures. Results: In the last decade, there has been a great increase in the number of trials relevant to schizophrenia and an improvement in the accessibility to reports. The number of trials per year is rising (currently ∼600/year) with China now producing 25% of the annual total. The number of reports of trials is increasing at an even greater rate due to multiple publications. Drug trials still dominate (83%) although an increasing proportion of studies are now evaluating psychological therapies (21%). Trials remain small (median 60 people) and often employ new nonvalidated outcomes scales (2194 different scales were employed with every fifth trial introducing a new rating instrument). Conclusions: A more collaborative, pragmatic, and patient-centered approach is necessary to produce larger schizophrenia trials. Wider consultation and careful consideration of all relevant perspectives would result in trials with greater clinical utility and direct value to people with the illness and their families or carers.
 
The numbers of included studies are indicated for each brain region (N). Abbreviations : ICV, intracranial volume; TBV, total brain volume; GM, total gray matter volume; WM, total white matter volume; CSF, total cerebrospinal fluid volume. 
Each circle represents a study sample. The circle size corresponds to relative weight assigned to the individual study. Excluding the study with the largest illness duration (panel A) did not reverse statistical significance. 
Article
Although structural brain alterations in schizophrenia have been demonstrated extensively, their quantitative distribution has not been studied over the last 14 years despite advances in neuroimaging. Moreover, a volumetric meta-analysis has not been conducted in antipsychotic-naive patients. Therefore, meta-analysis on cross-sectional volumetric brain alterations in both medicated and antipsychotic-naive patients was conducted. Three hundred seventeen studies published from September 1, 1998 to January 1, 2012 comprising over 9000 patients were selected for meta-analysis, including 33 studies in antipsychotic-naive patients. In addition to effect sizes, potential modifying factors such as duration of illness, sex composition, current antipsychotic dose, and intelligence quotient matching status of participants were extracted where available. In the sample of medicated schizophrenia patients (n = 8327), intracranial and total brain volume was significantly decreased by 2.0% (effect size d = -0.17) and 2.6% (d = -0.30), respectively. Largest effect sizes were observed for gray matter structures, with effect sizes ranging from -0.22 to -0.58. In the sample of antipsychotic-naive patients (n = 771), volume reductions in caudate nucleus (d = -0.38) and thalamus (d = -0.68) were more pronounced than in medicated patients. White matter volume was decreased to a similar extent in both groups, while gray matter loss was less extensive in antipsychotic-naive patients. Gray matter reduction was associated with longer duration of illness and higher dose of antipsychotic medication at time of scanning. Therefore, brain loss in schizophrenia is related to a combination of (early) neurodevelopmental processes-reflected in intracranial volume reduction-as well as illness progression.
 
Article
This article is based on my own personal experience of having undergone “coma treatment” and being given approximately 37 coma injections between the period 1983–1993 despite the fact that I was not psychotic and was normal in every way. The experiences I had following the injections and the forcible administration of innumerable antipsychotics and drugs have shaped my perspective of what it is to be a victim of “iatrogenic” psychiatric treatment—iatrogenic because it induced symptoms of schizophrenia or at the least schizoidism in a normal person like me—an inability to think, feel, and reason, over time. I have also with my own eyes seen at least 7 or 8 women who look me (my clones) that has reinforced my belief that the injections split me. The British psychiatrist, Richard David Laing (Encyclopedia Britannica 2004 DVD [DVD]) also theorized that it is the division of the self that leads to the symptoms of schizophrenia such as splitting and fragmentation of the mind.
 
Article
Torrey and Yolken wonder whether the killing of mentally ill persons in Nazi Germany reduced the risk for schizophrenia in the following generation. Epidemiological data from Germany do not permit reliable comparisons. Torrey and Yolken point out that horrible crime is still only little known. Strous and several contributors on the Schizophrenia Research Forum confirm that view. The history of ideas shows that social Darwinism in the educated classes and the doctrine of degeneration in psychiatry widely influenced thinking prior to World War II. Psychiatrists, lacking effective treatment for steadily growing numbers of the mentally ill, were susceptible to these ideologies. In a first step, several countries introduced compulsory sterilization as a genetic means of preventing diseases believed to be hereditary. Hitler's megalomaniac idea of creating a new human species by steering human evolution through the elimination of “unfit” genes in the mentally ill and inferior races led to the breach of human rights. His euthanasia program—the biggest crime ever perpetrated on the sick—turned out to usher in the gas chambers of the Holocaust.
 
Mean Scores, SD, and Statistics of the Main Outcome Measures
Logistic Regression Model: Variables Prediction Presence/Absence of Auditory Verbal Hallucinations
Article
Epidemiological studies suggest that auditory verbal hallucinations (AVH) occur in approximately 10%-15% of the general population, of whom only a small proportion has a clinically relevant psychotic disorder. It is unclear whether these hallucinations occur as an isolated phenomenon or if AVH in nonclinical individuals are part of a more general susceptibility to schizophrenia. For this study, 103 healthy individuals with frequent AVH were compared with 60 controls matched for sex, age, and education. All participants were examined by a psychiatrist using standardized diagnostic interviews and questionnaires. The individuals with AVH did not have clinically defined delusions, disorganization, or negative or catatonic symptoms, nor did they meet criteria for cluster A personality disorder. However, their global level of functioning was lower than in the controls and there was a pronounced increase on all subclusters of the Schizotypal Personality Questionnaire (SPQ) and the Peters Delusion Inventory, indicating a general increased schizotypal and delusional tendency in the hallucinating subjects. History of childhood trauma and family history of axis I disorders were also more prevalent in these individuals. We showed that higher SPQ scores, lower education, and higher family loading for psychiatric disorders, but not presence of AVH, were associated with lower global functioning. Our data suggest that AVH in otherwise healthy individuals are not an isolated phenomenon but part of a general vulnerability for schizophrenia.
 
Article
The "social brain" of humans reflects widespread neural resources dedicated to understanding the conversational language, emotionality, states of mind, and intentions of other persons. A social deafferentation (SDA) hypothesis for induction of active schizophrenia is proposed. Analogous to hallucinations produced by sensory deafferentation, such as phantom limb, the SDA hypothesis assumes that high levels of social withdrawal/isolation in vulnerable individuals prompt social cognition programs to produce spurious social meaning in the form of complex, emotionally compelling hallucinations and delusions representing other persons or agents. Arguments against the SDA hypothesis are discussed, and predictions deriving from the hypothesis are offered.
 
Article
This editorial reflects the work of all of the members of the WHO Working Group on the Classification of Psychotic Disorders, which include Jonathan Burns (South Africa), Peter Falkai (Germany), Saeed Farooq (Pakistan), Wolfgang Gaebel, Chair (Germany), Silvana Galderisi (Italy), Philippa Garety (UK), Michael Green (USA), Assen Jablensky (Australia), Veronica Larach Walters (Chile), Toshimasa Maruta (Japan), and Pichet Udomratn (Thailand), assisted by WHO Secretariat members Geoffrey Reed and Shekhar Saxena and consultant Michael B. First. Jürgen Zielasek (Germany) is rapporteur for the Working Group. The views expressed in this editorial reflect the opinion of its author and, except as specifically noted, do not represent the official policies and positions of the Working Group, the Advisory Group for the Revision of ICD-10 Mental and Behavioural Disorders, or of WHO.
 
Article
The physical and psychological characteristics of hypotonic schizophrenic children are described. It is hypothesized that hypotonic schizophrenia constitutes a homogeneous subgroup within the schizophrenic spectrum. The criteria for diagnosing hypotonic schizophrenia are stated. By selecting a homogeneous subgroup of schizophrenic patients, investigators may improve the probability of identifying a common biochemical etiology within this subgroup.
 
Article
This study examined the course of illness and factors affecting it in schizophrenias with onset between the ages of 14 and 18. Noteworthy in comparison to findings from other followup studies is the higher proportion of chronic courses of illness, about 50 percent. In addition, the type of course of illness corresponds in general with the treatment status. A possible explanation for this observation is the early age of onset, at which point the patient has not yet developed a sufficient degree of social and emotional independence and maturity before developing a schizophrenic psychosis. The age of onset is also shown to be an important predictor for the overall course of illness, as in other studies.
 
Article
The development of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and International Classification of Diseases, Eleventh Edition, deserves a significant conceptual step forward. There is a clear need to improve and refine the current diagnostic criteria, but also to introduce dimensions, perhaps not as an alternative but rather as a useful complement to categorical diagnosis. Laboratory, family, and treatment response data should also be systematically included in the diagnostic assessment when available. We have critically reviewed the content, concurrent, discriminant, and predictive validity of bipolar disorder, and to overcome the validity problems of the current classifications of mental disorders, we propose a modular system which may integrate categorical and dimensional issues, laboratory data, associated nonpsychiatric medical conditions, psychological assessment, and social issues in a comprehensive and nevertheless practical approach.
 
1990 Subtype Usage 28.9% 
2001 Subtype Usage 13.7% 
2010 Subtype Usage 6.8% 
Article
The diagnoses of paranoia, catatonia, and hebephrenia preceded the use of dementia praecox and Bleuler's subsequent recognition of a heterogenous "Group of Schizophrenias." With some modification, traditional schizophrenia subtypes have been formalized for many years in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD) classification systems. While widely used in the past, it is not clear that the schizophrenia subtypes remain in wide use or are influential in 21st-century research and clinical practice, and especially in the scientific literature. A review of published articles reveals over the last 20 years (1990, 2000, 2010) the use of traditional subtypes in the literature has fallen from 27.7% to 9.8% to 6.5%. Thus, by 2010, the use of subtypes in the leading literature venues declined to <10%. These facts strongly support DSM-5 and ICD-11 proposed elimination of traditional schizophrenia subtypes from a research and evolving knowledge perspective because traditional subtypes are simply no longer being used much in the scientific literature.
 
Article
Stimulant drugs such as cocaine and amphetamine are among the most commonly abused substances by schizophrenic patients. This may be due in part to aspects of the illness and treatment side effects that impel patients to use dopamine agonist drugs. Dopaminergic neural systems have been shown to mediate both stimulant drug effects and schizophrenia. Because of the hypothesized overlap in the pathophysiology of schizophrenia and the neurobiological effects of chronic stimulant use, the potential for serious complication of the primary disease by substance abuse exists. This article reviews the neurobiological mechanisms of behavioral sensitization and neurotoxicity associated with chronic stimulant administration in the context of pathophysiological theories of schizophrenia. Discussion focuses on the potential impact of stimulant use on the disease process as well as the manifest phenomenology and course of schizophrenia.
 
Molecular Targets for Cognitive Enhancement in Schizophrenia 
Article
Cognitive impairment is a core feature of schizophrenia as deficits are present in the majority of patients, frequently precede the onset of other positive symptoms, persist even with successful treatment of positive symptoms, and account for a significant portion of functional impairment in schizophrenia. While the atypical antipsychotics have produced incremental improvements in the cognitive function of patients with schizophrenia, overall treatment remains inadequate. In recent years, there has been an increased interest in developing novel strategies for treating the cognitive deficits in schizophrenia, focusing on ameliorating impairments in working memory, attention, and social cognition. Here we review various molecular targets that are actively being explored for potential drug discovery efforts in schizophrenia and cognition. These molecular targets include dopamine receptors in the prefrontal cortex, nicotinic and muscarinic acetylcholine receptors, the glutamatergic excitatory synapse, various serotonin receptors, and the gamma-aminobutyric acid (GABA) system.
 
Binding Affinities of DAR-0100 at Striatal D 1 and D 2 Receptors K 0.5 (nM) 6 SEM 
Preclinical Paradigms of Relevance to Schizophrenia in Which Glycine Transport Inhibitors Have Been Shown to Potential Beneficial Effects 
Article
Wayne Fenton was a major driving force behind the establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia (TURNS) project mechanisms. These projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified 3 drug mechanisms of particular interest: cholinergic, dopaminergic, and glutamatergic. The TURNS project is designed to select potential cognitive-enhancing agents and evaluate their potential efficacy in the context of proof of concept or clinical efficacy trials. This article reviews the rationale for these 3 approaches and provides an update on the development of therapeutic agents, which act through one of these 3 mechanisms.
 
Comparison of Early Responders and Nonresponders on Baseline Demographic and Clinical Characteristics 
Comparisons of Early Responders and Early Nonresponders on Change in SF-36 Subscale and Composite Scores from Baseline to 8 Weeks 
Comparisons of Early Responders and Early Nonresponders on Perceptions of Medication Benefits and Estimated Health Care Costs Following 8 Weeks of Treatment 
Article
Early nonresponse to antipsychotics appears to predict subsequent nonresponse to treatment when assessed in randomized controlled trials of predominately acute inpatients treated for schizophrenia. This study assessed the predictive accuracy of early nonresponse to treatment and its clinical, functional, and economic ramifications in the naturalistic treatment of predominately chronic outpatients treated for schizophrenia. This post hoc analysis used data from a 1-year, randomized, open-label study of olanzapine, risperidone, and typical antipsychotics in the treatment of schizophrenia. If clinically warranted, patients could switch antipsychotics following 8 weeks of treatment. Patients completing 8 weeks of treatment (n = 443 of 664 enrollees) were included. Patients with early response (> or = 20% improvement from baseline on the Positive and Negative Syndrome Scale at 2 weeks) were compared with early nonresponders on symptom remission, functionality, perceptions of medication influence, and total health care costs at 8 weeks. Early response/nonresponse at 2 weeks predicted subsequent response/nonresponse at 8 weeks with a high level of accuracy (72%) and specificity (89%). After 8 weeks, early nonresponders were less likely to achieve symptom remission (P < .001), improved less on functional domains (P < .05), perceived medication as less beneficial (P = .004), and incurred total heath care costs over twice that of early responders ($4349 vs $2102, P = .010). In the usual care of schizophrenia patients, early nonresponse appears to reliably predict subsequent nonresponse to continued treatment with the same medication to be associated with poorer outcomes and higher health care costs. Identifying early nonresponders may minimize prolonging exposure to suboptimal or ineffective treatment strategies.
 
Article
Models of the neuronal mediation of psychotic symptoms traditionally have focused on aberrations in the regulation of mesolimbic dopaminergic neurons, via their telencephalic afferent connections, and on the impact of abnormal mesolimbic activity for functions of the ventral striatum and its pallidal-thalamic-cortical efferent circuitry. Repeated psychostimulant exposure models major aspects of the sensitized activity of ventral striatal dopaminergic transmission that is observed in patients exhibiting psychotic symptoms. Based on neuroanatomical, neurochemical, and behavioral data, the hypothesis that an abnormally reactive cortical cholinergic input system represents a necessary correlate of a sensitized mesolimbic dopaminergic system is discussed. Moreover, the abnormal cognitive mechanisms that contribute to the development of psychotic symptoms are attributed specifically to the aberrations in cortical cholinergic transmission and to its consequences on the top-down regulation of sensory and sensory-associational input functions. Experimental evidence from studies demonstrating repeated amphetamine-induced sensitization of cortical cholinergic transmission and the ability of antipsychotic drugs to normalize the activity of cortical cholinergic inputs, and from experiments indicating the attentional consequences of manipulations that increase the excitability of cortical cholinergic inputs, supports this hypothesis. Relevant human neuropathological and psychopharmacological data are discussed, and the implications of an abnormally regulated cortical cholinergic input system for pharmacological treatment strategies are addressed. Given the role of cortical cholinergic inputs in gating cortical information processing, even subtle changes in the regulation of this cortexwide input system that represent a necessary transsynaptic consequence of sensitized mesolimbic dopaminergic transmission profoundly contribute to the neuronal mediation of psychotic symptoms.
 
Article
Computer simulations of parallel distributed processing (PDP) neural networks have increased our understanding of brain functioning. This article reviews how PDP concepts can contribute to our understanding of schizophrenic symptoms. Psychotic states induced by phencyclidine and the adult form of metachromatic leukodystrophy, as well as neurometabolic studies, suggest that schizophrenia reflects a breakdown in communication between cortical areas. A computer simulation of this type of brain pathology has suggested two neurocognitive consequences: some cortical circuits will become functionally autonomous, and a subset of these circuits will yield "parasitic foci" that slavishly reproduce the same cognitive output. Delusions of control, paranoid delusions of the idee fixe type, thought broadcasting, "voices," and certain deficit symptoms are postulated outcomes of parasitic foci located at different levels of language processing. A neurodevelopmental model of impaired corticocortical communication is described, and this model's implications for further study are outlined.
 
Article
Background: Alterations in striatal dopamine neurotransmission are central to the emergence of psychotic symptoms and to the mechanism of action of antipsychotics. Although the functional integrity of the presynaptic system can be assessed by measuring striatal dopamine synthesis capacity (DSC), no quantitative meta-analysis is available. Methods: Eleven striatal (caudate and putamen) [(11)C/(18)F]-DOPA positron emission tomography studies comparing 113 patients with schizophrenia and 131 healthy controls were included in a quantitative meta-analysis of DSC. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors and tested as covariates. Hedges' g was used as a measure of effect size in Comprehensive Meta-Analysis. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was addressed with the Q statistic and I(2) index. Results: Patients and controls were well matched in sociodemographic variables (P > .05). Quantitative evaluation of publication bias was nonsignificant (P = .276). Heterogeneity across study was modest in magnitude and statistically nonsignificant (Q = 19.19; P = .078; I (2) = 39.17). Patients with schizophrenia showed increased striatal DSC as compared with controls (Hedges' g = 0.867, CI 95% from 0.594 to 1.140, Z = 6.222, P < .001). The DSC schizophrenia/control ratio showed a relatively homogenous elevation of around 14% in schizophrenic patients as compared with controls. DSC elevation was regionally confirmed in both caudate and putamen. Controlling for potential confounders such as age, illness duration, gender, psychotic symptoms, and exposure to antipsychotics had no impact on the results. Sensitivity analysis confirmed robustness of meta-analytic findings. Conclusions: The present meta-analysis showed consistently increased striatal DSC in schizophrenia, with a 14% elevation in patients as compared with healthy controls.
 
Performance on the California Verbal Learning Test (CVLT), Total Learning Trials (A1-A5), for the 3 Groups at T1 and T2. 
Diagnoses at T1 and T2 in the Schizophrenia Group 
Performance on the digit symbol subtest (Wechsler Intelligence Scale for Children-Revised [WISC-R] at T1/Wechsler Adult Intelligence Scale-Third Edition [WAIS-III] at T2) for the 3 Groups at T1 and T2. 
Neurocognitive Test Results at T1 and T2 
Performance on the Digit Repetition Without Distraction Test for the 3 Groups at T1 and T2. 
Article
The issue of neurodegeneration in schizophrenia is controversial. Although most studies indicate that neurocognitive deficits are relatively stable over the course of the illness, conclusions are limited by relatively short follow-up periods and absence of age-matched control groups. Furthermore, nearly all studies deal with adult-onset schizophrenia, and few studies have considered the possible effect of age of onset. The current study represents the first attempt to compare groups of adolescents with schizophrenia, attention deficit/hyperactivity disorder (ADHD), and normal controls on a comprehensive neurocognitive test battery in a longitudinal design over 13 years. In the baseline study, adolescents with schizophrenia were examined with a broad battery of neurocognitive tests. The comparison groups consisted of adolescents with ADHD and adolescents without a psychiatric diagnosis, between 12 and 18 years of age. In the follow-up study, the schizophrenia group consisted of 15 of the initial 19 individuals, the ADHD group of 19 of the 20 individuals, and the normal comparison group of all 30 individuals. They were reevaluated with the neurocognitive test battery and clinical measures. Subjects with schizophrenia showed a significant decline or arrest in neurocognitive functioning compared with the other 2 groups, particularly in verbal memory, attention, and processing speed. The impairments may be specific to early-onset schizophrenia due to interaction between ongoing brain maturation during adolescence and disease-related mechanisms and/or secondary to neuroleptic treatment in young age and/or social isolation.
 
Demographic and Clinical Characteristics of the Study Sample 
Classification of Radiological Abnormalities 
MRI Scans of Patients and Controls With Clinically Relevant Neuroradiological Abnormalities 
Article
Background The term psychosis refers to a combination of symptoms, without pointing to the origin of these symptoms. In a subset of psychotic patients, symptoms are attributable to an organic disease. It is important to identify these organic causes of psychosis early, as urgent treatment of the primary disease may be required. Some of these underlying organic disorders can be identified on magnetic resonance imaging (MRI) scans. Whether routine screening for all psychotic patients should therefore include MRI scans is still a matter of debate.Methods This study investigated the prevalence of clinically relevant abnormalities detected on MRI scans from psychotic patients and a matched control group. We could include MRI scans from 656 psychotic patients and 722 controls. The standard radiological reports of these scans were classified as normal, as a nonrelevant abnormality or as a clinically relevant brain abnormality by means of consensus, blind to diagnosis.ResultsA normal aspect of the brain was reported in 74.4% of the patients and in 73.4% of the controls. We found clinically relevant pathology in 11.1% of the patients and in 11.8% of the controls. None of the neuropathological findings observed in the patients was interpreted as a possible substrate for organic psychosis. Brain abnormalities that were classified as not clinically relevant were identified in 14.5% of the patients and in 14.8% of the controls.Conclusions This suggests that MRI brain scans are not an essential part of routine screening for psychotic patients. © The Author 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
 
Controlled double-blind studies of atypical drugs In schizophrenia 
Clinical profile of atypical antlpsychotic drugs 
Side-effect profile of atypical antlpsychotlc drugs 
Article
A workshop on "Antipsychotics: Past and Future" was convened by the National Institute of Mental Health (NIMH), Division of Services and Intervention Research (DSIR), on July 14, 1998, to review the results of recent antipsychotic drug research, discuss current standards of treatment, and identify areas needing further study. There has been a proliferation of new antipsychotic medications and a rapid increase in their clinical utilization. The new atypicals are beginning to supplant the older typical neuroleptic antipsychotics, and the scientific and ethical issues raised by this transition prompted the workshop. Given the apparent, albeit not fully defined, advantages of atypical drugs, particularly their safety profiles, the question is whether more comparisons with typical antipsychotics are warranted and whether clinical trial designs warrant (or would be justified in) the inclusion of typical drugs as standard active comparators. Workshop participants--including clinical researchers, patient advocates, bioethicists, and NIMH staff--discussed the conclusions drawn from current data, ethical issues for subjects in clinical trials, funding for ongoing studies using typical agents, and appropriate comparators for trials using atypical agents.
 
Article
Cerebral metabolic hypofrontality in schizophrenia is a controversial research finding. In this article we discuss some of the issues that fuel this controversy, and we speculate on the neural mechanisms that may be responsible for the finding. Most regional cerebral blood flow (rCBF) studies using radioactive xenon have found hypofrontality; the results of positron emission tomography (PET) studies have been less consistent. Several technical factors are discussed that might contribute to the inconsistencies, including airway artifacts with xenon, limitations of tomography in studying the cortex, and approaches to data analysis. The possibility that hypofrontality is a result of medication is also critically examined. The medication factor is still unclear, but most studies of patients before and after neuroleptic medication find that cerebral metabolism goes up, not down, after treatment. The role of patient behavior and experience during an rCBF or PET procedure is an important variable that has not been adequately controlled in most studies. We suggest that this has been the most important variable in interpreting cerebral metabolic data in schizophrenia. Studies of patients examined during a behavior that normally activates prefrontal cortex have consistently found hypofrontality. One theoretical mechanism that could account for hypofrontality as well as many clinical and research findings in schizophrenia is dysfunction of dopaminergic neural transmission at the level of the prefrontal cortex.
 
Article
This prospective research investigated the occurrence and persistence of depression during the longitudinal course of schizophrenia. The research goals were to (1) compare depression in schizophrenia with that in schizoaffective and major depressive disorders, (2) assess whether some schizophrenia patients are vulnerable to depression, and (3) assess the relationship of depression to posthospital adjustment in schizophrenia. A total of 70 schizophrenia, 31 schizoaffective depressed, 17 psychotic unipolar major depressed, and 69 nonpsychotic unipolar major depressed patients were assessed during hospitalization and prospectively assessed for depression, psychosis, and posthospital functioning at 4.5- and 7.5-year followups. A large number (30% to 40%) of schizophrenia patients evidenced full depressive syndromes at each followup, including a subgroup of patients who evidenced repeated depression. Even when considering the influence of psychosis on outcome, depression in schizophrenia was associated with poor overall outcome, work impairment, lower activity, dissatisfaction, and suicidal tendencies. During the post-acute phase assessed, neither the rates nor the severity of depressive syndromes differentiated depression in schizophrenia from schizodepressive or major depressive disorders. However, the depressed schizophrenia patients showed poorer posthospital adjustment in terms of less employment, more rehospitalizations, and more psychosis than the patients with primary major depression. The high prevalence of depression in schizophrenia warrants its incorporation into theory about the disorder. A continuum of vulnerability to depression contributes to the heterogeneity of schizophrenia, with some schizophrenia patients being prone to depression even years after the acute phase. Depression in schizophrenia is one factor, in addition to psychosis, associated with poor outcome and requires specific attention to the treatment strategies by psychiatrists.
 
Mean Reaction Time (RT, 6SD) in Schizophrenic Patients (SZP) and Healthy Controls (HC).
Demographic and Clinic Characteristics of Schizophrenic Patients (SZP) and Healthy Controls (HC)
Mean Conflict Effect Scores (6SD) in Schizophrenic Patients (SZP) and Healthy Controls (HC).
Catechol- o -methyltransferase Val 108/158 Met Genotype 
Sex-and Group-Dependent Impact of catechol-omethyltransferase Val 108/158 Met Genotype on Conflict Effect in Schizophrenic Patients (SZP) and Healthy Controls (HC). Conflict effect (6SE) for each group (means and SD for each are given in Table A of Supplementary Material).
Article
Executive control of attention in schizophrenia has recently been assessed by means of the Attention Network Test (ANT). In the past, for tasks assessing executive attention, findings in schizophrenia have been contradictory, among others suggesting a lack of increased stimulus interference effects. Attention and executive functioning are substantially influenced by candidate genes of schizophrenia, including the functional single-nucleotide polymorphism catechol-o-methyltransferase (COMT) Val108/158Met, with task-dependent, specific effects of Met allele load on cognitive function. Therefore, we aimed at investigating executive attention in schizophrenic patients (SZP) as compared with healthy controls (HC), and to assess the specific impact of COMT Val108/158Met on executive attention, using ANT. We applied ANT to 63 SZP and 40 HC. We calculated a general linear model to investigate the influence of affection status and the COMT Val108/158Met genotype on executive attention as assessed by the ANT. Multivariate analysis of variance revealed a significant effect of group on executive attention. SZP exhibited smaller conflict effects in the ANT. Met allele load significantly modulated executive attention efficiency, with homozygous Met individuals showing low overall reaction time but increased effects conflicting stimulus information in executive attention. Our data suggest a disease-related dissociation of executive attention with reduced conflict effects in SZP. Furthermore, they support the hypothesis of differential tonic-phasic dopamine activation and specific dopamine level effects in different cognitive tasks, which helps interpreting contradictory findings of Met allele load on cognitive performance. Disease status seems to modulate the impact of COMT Val108/158Met on cognitive performance.
 
Article
Background: Rare copy number variations (CNVs) were involved in the etiology of neuropsychiatric disorders, and some of them appeared to be shared risk factors for several different diseases. One of those promising loci is the CNV at 15q11.2, including 4 genes, TUBGCP5, CYFIP1, NIPA2, and NIPA1. Several studies showed that microdeletions at this locus were significant associated with schizophrenia. In the current study, we investigated the role of both rare CNVs and common single nucleotide polymorphisms (SNPs) at 15q11.2 in schizophrenia in the Chinese Han population. Methods: We screened deletions at 15q11.2 in 2058 schizophrenia patients and 3275 normal controls in Chinese Han population by Affymetrix 500K/6.0 SNP arrays and SYBR green real-time polymerase chain reaction and then validated deletions by multiplex ligation-dependent probe amplification and Taqman real-time assays. We successfully genotyped 27 tag SNPs in total and tested associations in 1144 schizophrenia cases and 1144 normal controls. Results: We found a triple increase of deletions in cases over controls, with OR=4.45 (95% CI=1.36-14.60) and P=.014. In the analysis of common SNPs, we found that the most significant SNP in schizophrenia was rs4778334 (OR=.72, 95% CI=0.60-0.87, allelic P=.0056 after permutation, genotypic P=.015 after permutation). We also found SNP rs1009153 in CYFIP1 was associated with schizophrenia (OR=0.82, 95% CI=0.73-0.93, allelic P=.044 after permutation). Conclusion: We found that both rare deletions and common variants at 15q11.2 were associated with schizophrenia in the Chinese Han population.
 
Article
The 15-year hospitalization course of 646 chronic schizophrenic outpatients treated between 1958 and 1963 was determined using records of the research clinic, the Kings County Psychiatric Hospital, and the New York State Department of Mental Hygiene. The cohort was heterogeneous with regard to previous history of hospitalization: 20.6 percent had never been hospitalized, 22.0 percent had experienced only crisis admissions, and 57.4 percent had experienced long-term psychiatric hospitalization. The results indicate that 58.8 percent were hospitalized subsequent to project entry. A relationship was observed between previous history of hospitalization and hospitalization during the followup period. Patients with no previous history of hospitalization were less likely to be hospitalized than patients with crisis admissions only, who in turn were less likely to be hospitalized than patients with a history of hospitalization in a long-term psychiatric treatment facility (39.1 percent vs. 53.5 percent vs. 67.9 percent; p < .001). The implications of these findings for future followup studies are discussed.
 
Article
The Sixth International Congress on Schizophrenia Research (ICOSR) took place in Colorado Springs, Colorado, April 12-16, 1997, where over 1,000 scientists presented and listened to the latest developments in the search for the cause and treatment of schizophrenia. The ICOSR is sponsored by Maryland Psychiatric Research Center, Case Western Reserve University, and the William K. Warren Foundation. The National Institute of Mental Health and several pharmaceutical companies contributed generously to the meeting. The ICOSR is co-organized by Dr. Carol A. Tamminga, Maryland Psychiatric Research Center, University of Maryland at Baltimore, and Dr. S. Charles Schulz, Case Western Reserve University, Cleveland, Ohio. The William K. Warren Research Award is given to a senior investigator, who has made outstanding contributions to our understanding of schizophrenia. The fifth William K. Warren Research Award was presented to Dr. Philip S. Holzman in recognition of his contributions to the identification of eye-tracking abnormalities as a potential phenotypic marker of the illness and also in recognition of his work as a lifelong mentor for schizophrenia researchers. The ICOSR Young Investigator Awards are presented to junior investigators who have demonstrated the potential to make significant contributions to research on schizophrenia. These awards promote scientific development by enabling these young researchers to attend the meeting. There were 30 Young Investigator Award winners. The ICOSR meeting is organized into four sessions: (1) a morning plenary session; (2) a plenary lecture; (3) a poster session; and (4) concurrent afternoon oral sessions. The morning plenary sessions are comprised of a set of 30-minute lectures, which provide an overview of a particular topic area relevant to schizophrenia research. The plenary lecture is an invited lecture on a basic topic related to current research efforts in schizophrenia. The poster sessions provide a forum for the presentation of prepublication reports of basic and clinical science projects. The afternoon sessions are a collection of approximately 10 focused presentations on current research projects related to a specific topic area. The purpose of this report is to provide an account of the proceedings from the plenary and afternoon oral sessions.
 
Article
Gender differences have been noted in neurobehavioral studies. The 133xenon inhalation method for measuring regional cerebral blood flow (rCBF) can contribute to the understanding of the neural basis of gender differences in brain function. Few studies have examined gender differences in rCBF. In studies of normal subjects, women have higher rates of CBF than men, and this is related to age. Usually by the sixth decade men and women have similar flow rates. Fewer studies on rCBF in schizophrenia have examined sex differences. The pattern of higher flows for females maintains, but its correlates with gender differences in clinical as well as other parameters of brain function remain to be examined.
 
presents the results of 
Article
We have reviewed the literature from the 1950's to the present on the effects of neuroleptics on perceptual and neuropsychological function in chronic schizophrenic patients. In contrast to previous reviews, we have delineated the acute and chronic effects of neuroleptics on individual cognitive and motor tasks by drug, dose, and length of administration. To date, studies have shown that acute administration of neuroleptics impairs performance on some, but not all, tasks requiring vigilance and attention, and on some tasks requiring motor behavior. Chronic administration of neuroleptics, however, improves performance on some tasks requiring sustained attention and visuomotor problem-solving skills depending on dose and length of administration. Moreover, there is consistent evidence to suggest that chronic administration of neuroleptics in this patient population does not impair neuropsychological function independent of motor function. These findings have direct implications regarding the risk/benefit ratio and legal ramifications for the use of neuroleptics in chronic schizophrenic patients.
 
Article
This article presents a report on the first meeting of the International Consortium on Hallucination Research, which took place on September 13-14, 2011 at the Institute of Psychiatry, London. The first day of the meeting served to reflect on the current state of knowledge regarding auditory hallucinations in different diagnostic groups, based on the presentations from the phenomenology, cognition, emotion, electrophysiology, neurochemical, neuroimaging, genetics, treatment, and computational modeling working groups. The second day comprised a discussion forum where the most important and urgent questions for future research were identified. The meeting recognized that a lot has been achieved in auditory hallucination research but that much still remains to be done. Here, we outline the top 16 goals for research on auditory hallucinations, which cover topics of conceptual importance, academic and treatment issues, scientific rigor, and cross-disciplinary collaboration. Concerted and coordinated actions will be required to make substantial research progress.
 
Article
In order to bring about implementation of routine screening for psychosis risk, a brief version of the Prodromal Questionnaire (PQ; Loewy et al., 2005) was developed and tested in a general help-seeking population. We assessed a consecutive patient sample of 3533 young adults who were help-seeking for nonpsychotic disorders at the secondary mental health services in the Hague with the PQ. We performed logistic regression analyses and CHi-squared Automatic Interaction Detector decision tree analysis to shorten the original 92 items. Receiver operating characteristic curves were used to examine the psychometric properties of the PQ-16. In the general help-seeking population, a cutoff score of 6 or more positively answered items on the 16-item version of the PQ produced correct classification of Comprehensive Assessment of At-Risk Mental State (Yung et al., 2005) psychosis risk/clinical psychosis in 44% of the cases, distinguishing Comprehensive Assessment of At-Risk Mental States (CAARMS) diagnosis from no CAARMS diagnosis with high sensitivity (87%) and specificity (87%). These results were comparable to the PQ-92. The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk. The low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services.
 
Descriptives
Interscale Correlations Between Psychotic Experiences in Adolescence
Correlations Between Psychotic Experiences and Anxiety, Depression, and Personality
Scree plot from principal component analysis.
Article
We aimed to characterize multiple psychotic experiences, each assessed on a spectrum of severity (ie, quantitatively), in a general population sample of adolescents. Over five thousand 16-year-old twins and their parents completed the newly devised Specific Psychotic Experiences Questionnaire (SPEQ); a subsample repeated it approximately 9 months later. SPEQ was investigated in terms of factor structure, intersubscale correlations, frequency of endorsement and reported distress, reliability and validity, associations with traits of anxiety, depression and personality, and sex differences. Principal component analysis revealed a 6-component solution: paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and parent-rated negative symptoms. These components formed the basis of 6 subscales. Correlations between different experiences were low to moderate. All SPEQ subscales, except Grandiosity, correlated significantly with traits of anxiety, depression, and neuroticism. Scales showed good internal consistency, test-retest reliability, and convergent validity. Girls endorsed more paranoia, hallucinations, and cognitive disorganization; boys reported more grandiosity and anhedonia and had more parent-rated negative symptoms. As in adults at high risk for psychosis and with psychotic disorders, psychotic experiences in adolescents are characterized by multiple components. The study of psychotic experiences as distinct dimensional quantitative traits is likely to prove an important strategy for future research, and the SPEQ is a self- and parent-report questionnaire battery that embodies this approach.
 
Article
NPAS3 is a developmentally important transcription factor that has been associated with psychiatric illness. Our aim is to better define the regulation of NPAS3 mRNA (messenger RNA) levels during normal human prefrontal cortical development and in schizophrenia. Utilizing postmortem tissue from 134 human brains, we assessed: 60 normal brains ranging in age from birth to adulthood, 37 chronic individuals with schizophrenia, and 37 matched controls. mRNA and microRNA (miRNA) expressions were measured by microarray and quantitative real-time PCR. Protein expression was measured by Western blotting. During human postnatal cortical development (neonate to adult), we found decreased NPAS3 mRNA yet increased NPAS3 protein expression, suggesting the involvement of posttranscriptional regulation. Through screening, we identified one NPAS-targeted miRNA (miR-17) that changed in a pattern consistent with the developmental regulation of NPAS3. Using luciferase reporter assays, we assessed the impact of miR-17 on NPAS3 translation and demonstrated that miR-17 alters NPAS3 biosynthesis by binding to the NPAS3 3'untranslated region (UTR). In schizophrenia prefrontal cortex, we found significant elevations in miR-17 expression. While NPAS3 mRNA was unaltered, reduced NPAS3 protein expression was detected in a subpopulation of people with schizophrenia. The reciprocal expression of NPAS3 mRNA and protein during postnatal development mediated by a schizophrenia-associated change in miR-17 suggests that there is complex control over NPAS3 synthesis in the human prefrontal cortex and that if NPAS3 is dysregulated in schizophrenia, it is not evident by large changes in NPAS3 expression. Further studies into how changes in NPAS3 or its miRNA regulator may influence the development of schizophrenia are warranted.
 
Article
The aim of this study was to investigate interactional factors related to the recognition of suicide risk in patients with schizophrenia. The study focused on 17 schizophrenia patients who had committed suicide during the National Suicide Prevention Project in Finland between April 1, 1987, and March 31, 1988, in the province of Kuopio. Consensus case reports were assembled by using the psychological autopsy method. Study methods included structured and in-depth interviews of next of kin and interviews of health care or social services workers who had treated the suicide victims. Male and female patients with schizophrenia committed suicide in equal proportions. Most had suffered from schizophrenia for more than 15 years; all but one had been receiving psychiatric treatment at the time of suicide. Retrospective assessment indicated that 59 percent of the patients were clinically depressed at the time of suicide. In 76 percent of the cases, the mental health professionals involved in treatment had not believed that there was a risk of suicide during their last contact with the patient. In 29 percent of the cases, the patient's paranoid ideas concerning treatment personnel had increased. Patients' withdrawal from human relationships because of depression was related to loss of the treatment professionals' concern for the patients. The findings in this descriptive study suggest that withdrawal by a patient with schizophrenia and an increase in the patient's paranoid behavior should be regarded as signals of risk of suicide.
 
Article
This cross-sectional study examined the relationships between neurocognitive and social functioning in a sample of 80 outpatients with DSM-III-R schizophrenia. The neurocogrntive battery included measures of verbal ability, verbal memory, visual memory, executive functioning, visual-spatial organization, vigilance, and early information processing. Positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale. A range of social behaviors were assessed using the Social Functioning Scale (SFS), the Quality of Life Scale (QLS), and a video-based test, the Assessment of Interpersonal Problem-Solving Skills (AIPSS). Social functioning as assessed by the SFS was unrelated to neurocognitive functioning. Poor cognitive flexibility was associated with low scores on the QLS and the AIPSS. Verbal ability and verbal memory were also significantly associated with the AIPSS. Visual-spatial ability and vigilance were associated with the sending skills subscale of the ALPSS. In this study, which used a wide range of neurocognitive tests and measures of community functioning and social problem solving, results support earlier research that suggests an association between certain aspects of neurocognitive functioning and social functioning.
 
Article
This study was designed to examine disorder of switching attention in normal individuals with schizotypal personality. High scorers on the physical anhedonia (PA) and schizophrenism (SZ) scales of a questionnaire constructed to measure schizotypy were compared with a group of control subjects. A reaction time test was used that required switching attention across or between auditory and visual modalities. It was found that the high PA scorers and the high SZ scorers showed a deficit of shifting attention across modalities compared with the control subjects.
 
Region of interest (ROI) placement for PET analysis, which was defined using the Anatomical Automated Labeling Atlas. From above, caudate, putamen, nucleus accumbens, hippocampus, and parahippocampal gyrus in both hemispheres.
Article
Background: Altered transmission of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, may contribute to the development of schizophrenia. The purpose of the present study was to investigate the presence of GABA-A/benzodiazepine (BZ) receptor binding abnormalities in individuals at ultra-high risk (UHR) for psychosis in comparison with normal controls using [(18)F]-fluoroflumazenil (FFMZ) positron emission tomography (PET). In particular, we set regions of interest in the striatum (caudate, putamen, and nucleus accumbens) and medial temporal area (hippocampus and parahippocampal gyrus). Methods: Eleven BZ-naive people at UHR and 15 normal controls underwent PET scanning using [(18)F]-FFMZ to measure GABA-A/BZ receptor binding potential. The regional group differences between UHR individuals and normal controls were analyzed using Statistical Parametric Mapping 8 software. Participants were evaluated using the structured interview for prodromal syndromes and neurocognitive function tasks. Results: People at UHR demonstrated significantly reduced binding potential of GABA-A/BZ receptors in the right caudate. Conclusions: Altered GABAergic transmission and/or the imbalance of inhibitory and excitatory systems in the striatum may be present at the putative prodromal stage and play a pivotal role in the pathophysiology of psychosis.
 
Article
These interesting articles on cognitive deficits and rehabilitation in schizophrenic patients stimulate many questions, two of which are discussed in this reply. First, it seems likely that skepticism regarding the utilization and efficacy of cognitive rehabilitation strategies is born of despair that these treatments will ever be funded and delivered. This unfortunate state of affairs can only be corrected by effective social and political lobbying for adequate funding for mental health care. Second, the traditional tension between allocation and stage models of attention/information-processing deficits in schizophrenic patients may now be resolved by emerging theories that creatively integrate elements of stage and allocation theories. As we test these integrated theories, old “distinctions” seem to disappear and a clearer picture of information-processing dysfunctions in schizophrenic patients is emerging.
 
Article
Neuroinflammation and abnormal immune responses have been implicated in schizophrenia (SCZ). Past studies using positron emission tomography (PET) that examined neuroinflammation in patients with SCZ in vivo using the translocator protein 18kDa (TSPO) target were limited by the insensitivity of the first-generation imaging agent [(11)C]-PK11195, scanners used, and the small sample sizes studied. Present study uses a novel second-generation TSPO PET radioligand N-acetyl-N-(2-[(18)F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([(18)F]-FEPPA) to evaluate whether there is increased neuroinflammation in patients with SCZ. A cross-sectional study was performed using [(18)F]-FEPPA and a high-resolution research tomograph (HRRT). Eighteen patients with SCZ with ongoing psychotic symptoms and 27 healthy volunteers (HV) were recruited from a tertiary psychiatric clinical setting and the community, respectively. All participants underwent [(18)F]-FEPPA PET and magnetic resonance imaging, and PET data were analyzed to obtain [(18)F]-FEPPA total volume of distribution (V T) using a 2-tissue compartment model with an arterial plasma input function, as previously validated. All subjects were classified as high-, medium- or low-affinity [(18)F]-FEPPA binders on the basis of rs6971 polymorphism, and genotype information was incorporated into the analyses of imaging outcomes. No significant differences in neuroinflammation indexed as [(18)F]-FEPPA V T were observed between groups in either gray (F (1,39) = 0.179, P = .674) or white matter regions (F (1,38) = 0.597, P = .445). The lack of significant difference in neuroinflammation in treated patients with SCZ in the midst of a psychotic episode and HV suggests that neuroinflammatory processes may take place early in disease progression or are affected by antipsychotic treatment.
 
Striatal dopamine synthesis capacity ( K i cer value/min) for 
Clinical Characteristics of the Hallucinating Group
Article
Background: The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (using 6-[18F]fluoro-L-DOPA [[18F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.
 
Article
A prospective investigation using platelet monoamine oxidase activity and cortical evoked response augmenting/reducing to predict the onset of new episodes of affective disorders was conducted in a college sample. During an 18-month period between clinical interviews, higher incidences of major depression and hypomania characterized the low MAO/augmenting and the high MAO/reducing subjects. These same subgroups also had been associated with affective psychopathology in the original retrospective study.
 
Neurochemlcal studies of schizophrenia: Peptides 
Neuroendocrine studies of schizophrenia: Thyroid-releasing hormone (TRH) 
Article
Neurochemical investigation has played a major role in the search for the cause of schizophrenia. Initial research strategies involved the direct measurement of neurochemical substances in biological fluids. Subsequently, indirect measures of brain biochemistry including pituitary hormones and responses to pharmacologic probes were examined. Recent advances in in vivo functional neuroimaging, biochemical neuropathology, and molecular genetics have extended the scope of clinical neurochemical studies. The historical emphasis on the dopamine neurotransmitter system has subsided in the wake of the demonstrated limitations of the dopamine hypothesis of schizophrenia and increased evidence for the role of other neurotransmitters in the pathophysiology of schizophrenia as well as their interactions with dopamine neural systems. The neurotransmitters that have come under increasing scrutiny include serotonin, norepinephrine, glutamate, and related excitatory amino acids, and the neuropeptides cholecystokinin and neurotensin. In this article, the authors reviewed significant recently published neurochemical and neuroendocrine studies of schizophrenia in the context of previous work and found an extensive but fragmentary body of data which provides neither consistent nor conclusive evidence for any specific etiologic theory. Aspects of the disease and methodological limitations that may account for this as well as future research strategies are discussed.
 
Article
It is important to elaborate what we know about the symptomatic, syndromal, and functional course of schizophrenia in order to test models for this illness. The sample of schizophrenic patients from the Chestnut Lodge followup study was subtyped using classical (modified DSM-III-R) criteria and deficit/nondeficit (Schedule for the Deficit Syndrome) criteria. During the first 5 years of manifest illness, the subtype phenomenologies were moderately stable. Instability consisted of a drift toward disorganization (hebephrenia) and nonspecificity (undifferentiated) among the classical subtypes, and toward the deficit subtype within that categorization. Over the same time, positive symptoms were relatively stable, but negative symptoms became significantly worse. Such changes probably reflect "deterioration" because they were associated with poorer functional outcome an average of 15 years later. These data dovetail with other reports in the literature and suggest a hierarchy of symptomatic/syndromal progression in early manifest schizophrenia that may reflect active deterioration processes at work. We suggest that any theory of schizophrenic pathophysiology must account for these patterns of symptom course.
 
Kaplan-Meier survival curve for time (days) to admittance after index day for schizophrenia with the predictor verdict of any violent crime from index day. 
Cox regression analysis level I 1 
Cox regression analysis level II 1 
Article
Violent and aggressive behavior in preschizophrenia adolescents has been described in several studies. Our aim was to investigate the extent to which violent conviction in late adolescence predicted later schizophrenia in a cohort of young criminals. We performed a 9-year register-based followup of a complete national cohort of young convicted criminals. A total of 780, 15- to 19-year-old subjects identified in 1992 were followed up in 2001 with register linkage of the Danish Psychiatric Central Register, the Danish National Criminal Register, and the Danish National Cause of Death Register. Analyses with Cox regression were performed to identify predictors of later schizophrenia. We found at followup that 3.3 percent of the cohort had been diagnosed with schizophrenia and 4.5 percent with any psychosis. Conviction of violence in late adolescence was significantly associated (odds ratio = 4.59 [95% confidence interval (1.54; 13.74)]) with future diagnosis of schizophrenia. Violent behavior can thus be seen as part of the preschizophrenia phase of young criminals.
 
Conrad's Stage Model of Beginning Schizophrenia 
Article
Klaus Conrad's major contribution to the phenomenology of psychosis focused on the patient's experiences during the prodromal and early psychotic phases of schizophrenia. The literature in English concerning his work is sparse, in part because Conrad's work contains complex concepts that lose much in translation. This communication attempts to clarify Conrad's thought, especially as it pertains to the role of mood and delusions in beginning psychosis and its underlying neurobiology.
 
Article
On the 100th anniversary of the publication of Eugen Bleuler's Dementia Praecox or the Group of Schizophrenias, his teachings on schizophrenia from that seminal book are reviewed and reassessed, and implications for the current revision of the category of schizophrenia, with its emphasis on psychotic symptoms, drawn. Bleuler's methods are contrasted with Kraepelin's, and 4 myths about his concept of schizophrenia addressed. We demonstrate that (1) Bleuler's concept of schizophrenia has close ties to historical and contemporary concepts of dissociation and as such the public interpretation of schizophrenia as split personality has some historical basis; (2) Bleuler's concept of loosening of associations does not refer narrowly to a disorder of thought but broadly to a core organically based psychological deficit which underlies the other symptoms of schizophrenia; (3) the “4 A's,” for association, affect, ambivalence, and autism, do not adequately summarize Bleuler's teachings on schizophrenia and marginalize the central role of splitting in his conception; and (4) Bleuler's ideas were more powerfully influenced by Pierre Janet, particularly with regard to his diagnostic category Psychasthenia, than by Sigmund Freud. We conclude that Bleuler's ideas on schizophrenia warrant reexamination in the light of current criticism of the emphasis on psychotic symptoms in the schizophrenia diagnosis and argue for the recognition of the dissociative roots of this most important psychiatric category.
 
Article
In 1911, a book was published in Europe by Eugen Bleuler describing in detail asylum patients under his care who met clinical criteria for the psychotic disorder named Dementia Praecox by Emil Kraepelin. Bleuler's voluminous publication, now a classic to world psychiatry, validated Kraepelin's observations and extended them in ways that remain familiar to us a full century later in how we describe, diagnose, treat, and understand psychosis.
 
Top-cited authors
Lewis Alan Opler
  • Long Island University
Abraham Fiszbein
  • MountainView Regional Medical Center
Keith H Nuechterlein
  • University of California, Los Angeles
Kim Mueser
  • Boston University
Patrick D Mcgorry
  • Orygen The National Centre of Excellence in Youth Mental health